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Sample records for bovine articular cartilage

  1. Preliminary investigation of intrinsic UV fluorescence spectroscopic changes associated with proteolytic digestion of bovine articular cartilage

    Science.gov (United States)

    Lewis, William; Padilla-Martinez, Juan-Pablo; Ortega-Martinez, Antonio; Franco, Walfre

    2016-03-01

    Degradation and destruction of articular cartilage is the etiology of osteoarthritis (OA), an entity second only to cardiovascular disease as a cause of disability in the United States. Joint mechanics and cartilage biochemistry are believed to play a role in OA; an optical tool to detect structural and chemical changes in articular cartilage might offer benefit for its early detection and treatment. The objective of the present study was to identify the spectral changes in intrinsic ultraviolet (UV) fluorescence of cartilage that occur after proteolytic digestion of cartilage. Bovine articular cartilage samples were incubated in varying concentrations of collagenase ranging from 10ug/mL up to 5mg/mL for 18 hours at 37°C, a model of OA. Pre- and post-incubation measurements were taken of the UV excitation-emission spectrum of each cartilage sample. Mechanical tests were performed to determine the pre- and post-digestion force/displacement ratio associated with indentation of each sample. Spectral changes in intrinsic cartilage fluorescence and stiffness of the cartilage were associated with proteolytic digestion. In particular, changes in the relative intensity of fluorescence peaks associated with pentosidine crosslinks (330 nm excitation, 390 nm emission) and tryptophan (290 nm excitation, 340 nm emission) were found to correlate with different degrees of cartilage digestion and cartilage stiffness. In principle, it may be possible to use UV fluorescence spectral data for early detection of damage to articular cartilage, and as a surrogate measure for cartilage stiffness.

  2. Effects of electromagnetic fields on proteoglycan metabolism of bovine articular cartilage explants

    NARCIS (Netherlands)

    De Mattei, M; Pasello, M; Pellati, A; Stabellini, G; Massari, L; Gemmati, D; Caruso, A

    2003-01-01

    Electromagnetic field (EMF) exposure has been proposed for the treatment of osteoarthritis. In this study, we investigated the effects of EMF (75 Hz, 2,3 mT) on proteoglycan (PG) metabolism of bovine articular cartilage explants cultured in vitro, both under basal conditions and in the presence of

  3. Altered osmotic swelling behavior of proteoglycan-depleted bovine articular cartilage using high frequency ultrasound

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    Wang, Q; Zheng, Y P; Leung, G; Mak, A F T [Department of Health Technology and Informatics, Hong Kong Polytechnic University, Kowloon, Hong Kong (China); Lam, W L; Guo, X [Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong (China); Lu, H B; Qin, L [Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong (China)], E-mail: ypzheng@ieee.org

    2008-05-21

    Swelling behavior is an electrochemical mechanical property of articular cartilage. It plays an important role in weight bearing and joint lubrication. In this study, the altered transient and inhomogeneous swelling behavior of the degenerated articular cartilage was observed and quantified in situ using ultrasound. Three groups of bovine patellar articular cartilage samples (n = 10 x 3) were obtained and digested by trypsin for 10, 20 and 30 min respectively to mimic different levels of degeneration. The osmotic-free shrinkage and swelling behavior induced by changing the concentration of the bathing saline solution from 0.15 M to 2 M and then back to 0.15 M were characterized using high-frequency ultrasound (central frequency = 35 MHz) before and after digestion. It was found that the degenerated cartilage specimens showed a weaker shrinkage-swelling behavior compared with the normal cartilage samples. However, no significant differences in the peak shrinkage or swelling strains were observed between different groups. The absolute values of the peak shrinkage strain significantly (p < 0.05) decreased by 45.4%, 42.1% and 50.6% respectively after the trypsin digestion for 10, 20 and 30 min, but such significance was not demonstrated for the peak swelling strains. Due to the potential alterations in the collagen-PG matrix during trypsin digestion, the correlation between the swelling strain and the shrinkage strain of the degenerated samples changed slightly in comparison with the normal samples. The proposed ultrasound method has been successfully used to measure the transient and inhomogeneous swelling behavior of the degenerated articular cartilage and has the potential for the characterization of osteoarthritis.

  4. Effect of retinoic acid on proteoglycan turnover in bovine articular cartilage cultures

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    Campbell, M.A.; Handley, C.J.

    1987-10-01

    This paper describes proteoglycan catabolism by adult bovine articular cartilage treated with retinoic acid as a means of stimulating the loss of this macromolecule from the extracellular matrix of cartilage. Addition of retinoic acid (10(-12)-10(-6) M) to adult bovine articular cartilage which had been labeled with (/sup 35/S)sulfate for 6 h after 5 days in culture, resulted in a dose-dependent increase in the rate of loss of /sup 35/S-labeled proteoglycans from the matrix of the tissue. Concomitant with this loss was a decrease in the proteoglycan content of the tissue. Incubation of cultures treated with 1 microM retinoic acid, at 4 degrees C, or with 0.5 mM cycloheximide, resulted in a significant decrease in the rate of retinoic acid-induced loss of proteoglycans and demonstrated cellular involvement in this process. Analysis of the /sup 35/S-labeled proteoglycans remaining in the matrix showed that the percentage of radioactivity associated with the small proteoglycan species extracted from the matrix of articular cartilage explants labeled with (/sup 35/S)sulfate after 5 days in culture was 15% and this increased to 22% in tissue maintained in medium alone. In tissue treated with 1 microM retinoic acid for 6 days, the percentage of radioactivity associated with the small proteoglycan was 58%. Approximately 93% of the /sup 35/S-labeled proteoglycans released into the medium of control and retinoic acid-treated cultures was recovered in high density fractions after CsCl gradient centrifugation and eluted on Sepharose CL-2B as a broad peak with a Kav of 0.30-0.37. Less than 17% of these proteoglycans was capable of aggregating with hyaluronate. These results indicate that in both control and retinoic acid-treated cultures the larger proteoglycan species is lost to the medium at a greater rate than the small proteoglycan species. The effect of retinoic acid on proteoglycan turnover was shown to be reversible.

  5. Tensorial Electrokinetics in Articular Cartilage

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    Reynaud, Boris; Quinn, Thomas M.

    2006-01-01

    Electrokinetic phenomena contribute to biomechanical functions of articular cartilage and underlie promising methods for early detection of osteoarthritic lesions. Although some transport properties, such as hydraulic permeability, are known to become anisotropic with compression, the direction-dependence of cartilage electrokinetic properties remains unknown. Electroosmosis experiments were therefore performed on adult bovine articular cartilage samples, whereby fluid flows were driven by electric currents in directions parallel and perpendicular to the articular surface of statically compressed explants. Magnitudes of electrokinetic coefficients decreased slightly with compression (from ∼−7.5 μL/As in the range of 0–20% compression to −6.0 μL/As in the 35–50% range) consistent with predictions of microstructure-based models of cartilage material properties. However, no significant dependence on direction of the electrokinetic coupling coefficient was detected, even for conditions where the hydraulic permeability tensor is known to be anisotropic. This contrast may also be interpreted using microstructure-based models, and provides insights into structure-function relationships in cartilage extracellular matrix and physical mediators of cell responses to tissue compression. Findings support the use of relatively simple isotropic modeling approaches for electrokinetic phenomena in cartilage and related materials, and indicate that measurement of electrokinetic properties may provide particularly robust means for clinical evaluation of cartilage matrix integrity. PMID:16798804

  6. [Bionic design of articular cartilage].

    Science.gov (United States)

    Qin, Jun; Zhang, Wenguang; Wu, Gang; Wang, Chengtao

    2008-02-01

    Natural articular cartilage is well known as a special connective tissue with multiple effects and functions, which are important and irreplaceable, in human synovial joints. Biomedical, histological and pathological characteristics of articular cartilage, as well as biomaterial, biomechanical and bio-tribological properties thereof, are summarized from a novel aspect of bionics. Bionic design of articualr cartilage at macro-level and micro-level is carried out from three aspects, i.e., structure, material, and function; and a bionic design model of articular cartilage is set up. As a result, this basic research would be helpful to providing theoretical and practical basis for innovational design and manufacturing of new-style artificial joint with "soft-cushion bearing", and of bionic artificial cartilage.

  7. The effect of collagen degradation on chondrocyte volume and morphology in bovine articular cartilage following a hypotonic challenge.

    Science.gov (United States)

    Turunen, S M; Lammi, M J; Saarakkala, S; Han, S-K; Herzog, W; Tanska, P; Korhonen, R K

    2013-06-01

    Collagen degradation is one of the early signs of osteoarthritis. It is not known how collagen degradation affects chondrocyte volume and morphology. Thus, the aim of this study was to investigate the effect of enzymatically induced collagen degradation on cell volume and shape changes in articular cartilage after a hypotonic challenge. Confocal laser scanning microscopy was used for imaging superficial zone chondrocytes in intact and degraded cartilage exposed to a hypotonic challenge. Fourier transform infrared microspectroscopy, polarized light microscopy, and mechanical testing were used to quantify differences in proteoglycan and collagen content, collagen orientation, and biomechanical properties, respectively, between the intact and degraded cartilage. Collagen content decreased and collagen orientation angle increased significantly (p < 0.05) in the superficial zone cartilage after collagenase treatment, and the instantaneous modulus of the samples was reduced significantly (p < 0.05). Normalized cell volume and height 20 min after the osmotic challenge (with respect to the original volume and height) were significantly (p < 0.001 and p < 0.01, respectively) larger in the intact compared to the degraded cartilage. These findings suggest that the mechanical environment of chondrocytes, specifically collagen content and orientation, affects cell volume and shape changes in the superficial zone articular cartilage when exposed to osmotic loading. This emphasizes the role of collagen in modulating cartilage mechanobiology in diseased tissue.

  8. Articular cartilage bioreactors and bioprocesses.

    Science.gov (United States)

    Darling, Eric M; Athanasiou, Kyriacos A

    2003-02-01

    This review summarizes the major approaches for developing articular cartilage, using bioreactors and mechanical stimuli. Cartilage cells live in an environment heavily influenced by mechanical forces. The development of cartilaginous tissue is dependent on the environment that surrounds it, both in vivo and in vitro. Chondrocytes must be cultured in a way that gives them the proper concentration of nutrients and oxygen while removing wastes. A mechanical force must also be applied during the culturing process to produce a phenotypically correct tissue. Four main types of forces are currently used in cartilage-culturing processes: hydrostatic pressure, direct compression, "high"-shear fluid environments, and "low"-shear fluid environments. All these forces have been integrated into culturing devices that serve as bioreactors for articular cartilage. The strengths and weaknesses of each device and stimulus are explored, as is the future of cartilage bioreactors.

  9. Effect of partial H2O-D2O replacement on the anisotropy of transverse proton spin relaxation in bovine articular cartilage.

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    Sirisha Tadimalla

    Full Text Available Anisotropy of transverse proton spin relaxation in collagen-rich tissues like cartilage and tendon is a well-known phenomenon that manifests itself as the "magic-angle" effect in magnetic resonance images of these tissues. It is usually attributed to the non-zero averaging of intra-molecular dipolar interactions in water molecules bound to oriented collagen fibers. One way to manipulate the contributions of these interactions to spin relaxation is by partially replacing the water in the cartilage sample with deuterium oxide. It is known that dipolar interactions in deuterated solutions are weaker, resulting in a decrease in proton relaxation rates. In this work, we investigate the effects of deuteration on the longitudinal and the isotropic and anisotropic contributions to transverse relaxation of water protons in bovine articular cartilage. We demonstrate that the anisotropy of transverse proton spin relaxation in articular cartilage is independent of the degree of deuteration, bringing into question some of the assumptions currently held over the origins of relaxation anisotropy in oriented tissues.

  10. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a

  11. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

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    Robert Mark Wellard

    2014-05-01

    Full Text Available Magnetic resonance imaging (MRI offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP. MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer.

  12. INJURED ARTICULAR CARTILAGE REPAIR

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    Ariana Barlič

    2008-02-01

    Surveys show that the most frequently used surgical methods are mosaicplasty and bonemarrow stimulation with microfracturing. The efficacy of the autologous chondrocyte implantationmethod should be superior to microfracturing on a long run. Especially when(regeneration of the hyaline cartilage instead of fibrous tissue (fibrocartilage is concerned.However, it has not been scientifically proved yet

  13. Supporting Biomaterials for Articular Cartilage Repair

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    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  14. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics

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    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L.

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  15. Optical clearing of articular cartilage: a comparison of clearing agents

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    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  16. Advances in treatment of articular cartilage injuries

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    Yuan-cheng LI

    2013-05-01

    Full Text Available Cartilage is a kind of terminally differentiated tissue devoid of vessel or nerve, and it is difficult to repair by itself after damage. Many studies for the treatment of cartilage injuries were performed in recent years aiming at repair of the structure and restoration of its function for injured joint. This article reviews the traditional methods of treatment for cartilage injuries, such as joint lavage with the aid of arthroscope, abrasion chondroplasty, laser abrasion and chondroplasty, and drilling of the subchondral bone-marrow space. The research advances in treatment of articular cartilage injuries with tissue engineering were summarized.

  17. The minor collagens in articular cartilage

    DEFF Research Database (Denmark)

    Luo, Yunyun

    2017-01-01

    Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components......, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also...... fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including...

  18. Body weight independently affects articular cartilage catabolism.

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    Denning, W Matt; Winward, Jason G; Pardo, Michael Becker; Hopkins, J Ty; Seeley, Matthew K

    2015-06-01

    Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW) independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity). The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW), +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP) was measured immediately before (baseline) and after, and 15 and 30 minutes after the walk. Heart rate (HR) and rate of perceived exertion (RPE) were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response. Key pointsWalking for 30 minutes with adjustments in body weight (normal body weight, +40% and -40% body weight) significantly influences articular cartilage catabolism, measured via serum COMP concentration.Compared to baseline levels, walking with +40% body weight and normal body weight both elicited significant increases in

  19. Regulators of articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus

    2012-01-01

    Prevention of hypertrophic differentiation is essential for successful cartilage repair strategies. Although this process is essential for longitudinal growth, it also is part of degenerative cartilage diseases such as osteoarthiritis. Moreover, it limits the use of cell types prone to this process

  20. Biochemical composition of the superficial layer of articular cartilage.

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    Crockett, R; Grubelnik, A; Roos, S; Dora, C; Born, W; Troxler, H

    2007-09-15

    To gain more information on the mechanism of lubrication in articular joints, the superficial layer of bovine articular cartilage was mechanically removed in a sheet of ice that formed on freezing the cartilage. Freeze-dried samples contained low concentrations of chondroitin sulphate and protein. Analysis of the protein by SDS PAGE showed that the composition of the sample was comparable to that of synovial fluid (SF). Attenuated total reflection infrared (ATR-IR) spectroscopy of the dried residue indicated that the sample contained mostly hyaluronan. Moreover, ATR-IR spectroscopy of the upper layer of the superficial layer, adsorbed onto silicon, showed the presence of phospholipids. A gel could be formed by mixing hyaluronan and phosphatidylcholine in water with mechanical properties similar to those of the superficial layer on cartilage. Much like the superficial layer of natural cartilage, the surface of this gel became hydrophobic on drying out. Thus, it is proposed that the superficial layer forms from hyaluronan and phospholipids, which associate by hydrophobic interactions between the alkyl chains of the phospholipids and the hydrophobic faces of the disaccharide units in hyaluronan. This layer is permeable to material from the SF and the cartilage, as shown by the presence of SF proteins and chondroitin sulphate. As the cartilage dries out after removal from the joint, the phospholipids migrate towards the surface of the superficial layer to reduce the surface tension. It is also proposed that the highly efficient lubrication in articular joints can, at least in part, be attributed to the ability of the superficial layer to adsorb and hold water on the cartilage surface, thus creating a highly viscous boundary protection. Copyright 2007 Wiley Periodicals, Inc.

  1. Polarized IR microscopic imaging of articular cartilage

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    Ramakrishnan, Nagarajan; Xia Yang; Bidthanapally, Aruna [Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309 (United States)

    2007-08-07

    The objective of this spectroscopic imaging study is to understand the anisotropic behavior of articular cartilage under polarized infrared radiation at 6.25 {mu}m pixel resolution. Paraffin embedded canine humeral cartilage-bone blocks were used to obtain 6 {mu}m thick tissue sections. Two wire grid polarizers were used to manipulate the polarization states of IR radiation by setting them for various polarizer/analyzer angles. The characteristics of the major chemical components (amide I, amide II, amide III and sugar) of articular cartilage were investigated using (a) a polarizer and (b) a combination of a polarizer and an analyzer. These results were compared to those obtained using only an analyzer. The infrared anisotropy (variation in infrared absorption as a function of polarization angles) of amide I, amide II and amide III bands correlates with the orientation of collagen fibrils along the tissue depth in different histological zones. An 'anisotropic flipping' region of amide profiles indicates the possibility of using Fourier transform infrared imaging (FTIRI) to determine the histological zones in cartilage. Cross-polarization experiment indicates the resolution of overlapping peaks of collagen triple helix and/or proteoglycan in articular cartilage.

  2. Swelling and curling behaviors of articular cartilage.

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    Setton, L A; Tohyama, H; Mow, V C

    1998-06-01

    A new experimental method was developed to quantify parameters of swelling-induced shape change in articular cartilage. Full-thickness strips of cartilage were studied in free-swelling tests and the swelling-induced stretch, curvature, and areal change were measured. In general, swelling-induced stretch and curvature were found to increase in cartilage with decreasing ion concentration, reflecting an increasing tendency to swell and "curl" at higher swelling pressures. An exception was observed at the articular surface, which was inextensible for all ionic conditions. The swelling-induced residual strain at physiological ionic conditions was estimated from the swelling-induced stretch and found to be tensile and from 3-15 percent. Parameters of swelling were found to vary with sample orientation, reflecting a role for matrix anisotropy in controlling the swelling-induced residual strains. In addition, the surface zone was found to be a structurally important element, which greatly limits swelling of the entire cartilage layer. The findings of this study provide the first quantitative measures of swelling-induced residual strain in cartilage ex situ, and may be readily adapted to studies of cartilage swelling in situ.

  3. Investigation of polarization-sensitive optical coherence tomography towards the study of microstructure of articular cartilage

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    Kasaragod, Deepa; Lu, Zenghai; Le Maitre, Christine; Wilkinson, J. Mark; Matcher, Stephen

    2013-03-01

    This paper highlights the extended Jones matrix calculus based multi-angle study carried out to understand the depth dependent structural orientation of the collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography (PS-OCT). A 3D lamellar model for the collagen fiber orientation, with a quadratic profile for the arching of the collagen fibers in transitional zone which points towards an ordered arrangement of fibers in that zone is the basis of the organization architecture of collagen fibers in articular cartilage. Experimental data for both ex-vivo bovine fetlock and human patellar cartilage samples are compared with theoretical predictions, with a good quantitative agreement for bovine and a reasonable qualitative agreement for human articular cartilage samples being obtained

  4. PRP and Articular Cartilage: A Clinical Update

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    Antonio Marmotti

    2015-01-01

    Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

  5. Contrast agent enhanced pQCT of articular cartilage

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    Kallioniemi, A S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Jurvelin, J S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Nieminen, M T [Department of Diagnostic Radiology, POB 50, 90029 OYS, Oulu University Hospital, Oulu (Finland); Lammi, M J [Department of Anatomy, Institute of Biomedicine, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Toeyraes, J [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland)

    2007-02-21

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T{sub 1,Gd} and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  6. Contrast Agent-Enhanced Computed Tomography of Articular Cartilage: Association with Tissue Composition and Properties

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    Silvast, T.S.; Jurvelin, J.S.; Aula, A.S.; Lammi, M.J.; Toeyraes, J. (Dept. of Clinical Neurophysiology, Kuopio Univ. Hospital, Kuopio (Finland))

    2009-01-15

    Background: Contrast agent-enhanced computed tomography may enable the noninvasive quantification of glycosaminoglycan (GAG) content of articular cartilage. It has been reported that penetration of the negatively charged contrast agent ioxaglate (Hexabrix) increases significantly after enzymatic degradation of GAGs. However, it is not known whether spontaneous degradation of articular cartilage can be quantitatively detected with this technique. Purpose: To investigate the diagnostic potential of contrast agent-enhanced cartilage tomography (CECT) in quantification of GAG concentration in normal and spontaneously degenerated articular cartilage by means of clinical peripheral quantitative computed tomography (pQCT). Material and Methods: In this in vitro study, normal and spontaneously degenerated adult bovine cartilage (n=32) was used. Bovine patellar cartilage samples were immersed in 21 mM contrast agent (Hexabrix) solution for 24 hours at room temperature. After immersion, the samples were scanned with a clinical pQCT instrument. From pQCT images, the contrast agent concentration in superficial as well as in full-thickness cartilage was calculated. Histological and functional integrity of the samples was quantified with histochemical and mechanical reference measurements extracted from our earlier study. Results: Full diffusion of contrast agent into the deep cartilage was found to take over 8 hours. As compared to normal cartilage, a significant increase (11%, P<0.05) in contrast agent concentration was seen in the superficial layer of spontaneously degenerated samples. Significant negative correlations were revealed between the contrast agent concentration and the superficial or full-thickness GAG content of tissue (|R|>0.5, P<0.01). Further, pQCT could be used to measure the thickness of patellar cartilage. Conclusion: The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a

  7. Mesenchymal Stem Cells for Treating Articular Cartilage Defects and Osteoarthritis.

    Science.gov (United States)

    Wang, Yu; Yuan, Mei; Guo, Quan-yi; Lu, Shi-bi; Peng, Jiang

    2015-01-01

    Articular cartilage damage and osteoarthritis are the most common joint diseases. Joints are prone to damage caused by sports injuries or aging, and such damage regularly progresses to more serious joint disorders, including osteoarthritis, which is a degenerative disease characterized by the thinning and eventual wearing out of articular cartilage, ultimately leading to joint destruction. Osteoarthritis affects millions of people worldwide. Current approaches to repair of articular cartilage damage include mosaicplasty, microfracture, and injection of autologous chondrocytes. These treatments relieve pain and improve joint function, but the long-term results are unsatisfactory. The long-term success of cartilage repair depends on development of regenerative methodologies that restore articular cartilage to a near-native state. Two promising approaches are (i) implantation of engineered constructs of mesenchymal stem cell (MSC)-seeded scaffolds, and (ii) delivery of an appropriate population of MSCs by direct intra-articular injection. MSCs may be used as trophic producers of bioactive factors initiating regenerative activities in a defective joint. Current challenges in MSC therapy are the need to overcome current limitations in cartilage cell purity and to in vitro engineer tissue structures exhibiting the required biomechanical properties. This review outlines the current status of MSCs used in cartilage tissue engineering and in cell therapy seeking to repair articular cartilage defects and related problems. MSC-based technologies show promise when used to repair cartilage defects in joints.

  8. Articular Cartilage Regeneration: An Update of Possible Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Ray Marks

    2017-08-01

    Full Text Available BACKGROUND: Osteoarthritis, a widespread chronically disabling disorder primarily affecting articular cartilage is said to be irreversible. Researchers have however, been examining processes and methods of promoting articular cartilage repair for some time. QUESTIONS: Can a case be made for the possibility of restoring osteoarthritic cartilage? How advanced is this undertaking? What barriers exist in translating basic studies in the clinical realm? What physical modalities are deemed efficacious in promoting cartilage structure? METHODS: All relevant publications detailing articular cartilage repair themes in the leading databases were examined. Specific emphasis was placed on a broad array of efforts and observations concerning articular cartilage and its repair. Articles of historic significance and more current strategies designed to foster cartilage repair were focused on, and reported in narrative form. Ideas extracted from the voluminous literature were those that answered one or more of the key questions driving this research. RESULTS: Numerous attempts have been made over time to foster cartilage repair, using a variety of approaches such as creating artificial cartilage, and transplanting stem cells into damaged cartilage to promote repair. Most current strategies are forged in laboratories and do not always account for the complex disease process, and the importance mechanical and inflammatory determinants play in the disease. However, manipulating biophysical, and biomechanical stimuli favorably is likely to hold promise for attenuating destruction of/or for fostering cartilage viability and repair, even in the presence of adverse osteoarthritic cartilage tissue changes. CONCLUSION: More work is needed to examine the key upstream determinants leading to articular cartilage destruction, and to enhancing the viability of the tissue. Employing carefully construed therapeutic strategies known to impact articular cartilage homeostasis

  9. Direct Quantification of Solute Diffusivity in Agarose and Articular Cartilage Using Correlation Spectroscopy.

    Science.gov (United States)

    Shoga, Janty S; Graham, Brian T; Wang, Liyun; Price, Christopher

    2017-10-01

    Articular cartilage is an avascular tissue; diffusive transport is critical for its homeostasis. While numerous techniques have been used to quantify diffusivity within porous, hydrated tissues and tissue engineered constructs, these techniques have suffered from issues regarding invasiveness and spatial resolution. In the present study, we implemented and compared two separate correlation spectroscopy techniques, fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), for the direct, and minimally-invasive quantification of fluorescent solute diffusion in agarose and articular cartilage. Specifically, we quantified the diffusional properties of fluorescein and Alexa Fluor 488-conjugated dextrans (3k and 10k) in aqueous solutions, agarose gels of varying concentration (i.e. 1, 3, 5%), and in different zones of juvenile bovine articular cartilage explants (i.e. superficial, middle, and deep). In agarose, properties of solute diffusion obtained via FCS and RICS were inversely related to molecule size, gel concentration, and applied strain. In cartilage, the diffusional properties of solutes were similarly dependent upon solute size, cartilage zone, and compressive strain; findings that agree with work utilizing other quantification techniques. In conclusion, this study established the utility of FCS and RICS as simple and minimally invasive techniques for quantifying microscale solute diffusivity within agarose constructs and articular cartilage explants.

  10. Comparison of equine articular cartilage thickness in various joints.

    Science.gov (United States)

    Lee, Hyeon; Kirkland, W Grant; Whitmore, Ryan N; Theis, Kelcie M; Young, Hannah E; Richardson, Ashton J; Jackson, Robert L; Hanson, R Reid

    2014-01-01

    Thicknesses of fresh equine articular cartilage surfaces from the fetlock, carpal and stifle joints were measured employing a needle probe test. Eighty-seven samples used in measurement were cultivated from fetlock, carpal and stifle joints of 12 deceased within 4 h of death. After approximately three minutes of exposure to air during dissection, all cartilage samples were preserved in a saline solution to keep the articular cartilage hydrated for testing. The thickness was measured on five different spots on the same sample. The thicknesses of the fetlock, carpus and stifle were compared. The articular cartilage of the stifle was thicker than the fetlock and carpus, while the fetlock and the carpus had similar thickness values. The average thickness of the fetlock, carpal and stifle joint are 0.86, 0.87 and 2.1 mm, respectively. They were statistically compared using the Student t-test. The differences on the articular cartilage thicknesses between the fetlock and stifle, and carpus and stifle were "very highly significant" (p fetlock and carpus. Four different surfaces in the fetlock and four in the carpal joint were also compared. Significant differences between each set of the four surfaces were not observed. In the carpus, the difference in thickness between the distal radius and proximal third carpal bone articular cartilage surfaces as well as the proximal radial carpal bone and distal radial carpal bone articular cartilage surfaces were statistically significant.

  11. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    Science.gov (United States)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  12. REGENERATION OF ARTICULAR CARTILAGE UNDER THE IMPLANTATION OF BONE MATRIX

    Directory of Open Access Journals (Sweden)

    Yuri M. Iryanov, Nikolay A. Kiryanov, Olga V. Dyuriagina , Tatiana Yu. Karaseva, Evgenii A. Karasev

    2015-07-01

    Full Text Available Background: The damage or loss of articular cartilage is costly medical problem. The purpose of this work – morphological analysis of reparative chondrogenesis when implanted in the area of the knee joint cartilage of granulated mineralized bone matrix. Material and Methods: The characteristic features of the knee cartilage regeneration studied experimentally in pubertal Wistar rats after modeling a marginal perforated defect and implantation of granulated mineralized bone matrix obtained according to original technology without heat and demineralizing processing into the injury zone. Results: This biomaterial established to have pronounced chondro- and osteoinductive properties, and to provide prolonged activation of reparative process, accelerated organotypical remodeling and restoration of the articular cartilage injured. Conclusion: The data obtained demonstrate the efficacy of МВМ in clinical practice for the treatment of diseases and injuries of the articular cartilage.

  13. Leptin plays a catabolic role on articular cartilage.

    Science.gov (United States)

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA.

  14. Regional Articular Cartilage Abnormalities of the Hip.

    Science.gov (United States)

    Link, Thomas M; Schwaiger, Benedikt J; Zhang, Alan L

    2015-09-01

    Imaging of hip cartilage is challenging because of its limited thickness and complex geometry and therefore requires advanced MRI techniques. However, cartilage abnormalities are found in a number of disease entities, and their diagnosis may impact patient management. This article will provide pertinent information about the motivation to image hip cartilage, which imaging techniques to use, and how to analyze cartilage; finally, we will discuss disease entities with regional cartilage lesions, including the typical MRI findings. Because the detection and quantification of regional cartilage abnormalities are critical for guidance of operative and nonoperative management of hip disorders, radiologists should be familiar with imaging and analysis techniques for assessing hip cartilage.

  15. Infrared microspectroscopic determination of collagen cross-links in articular cartilage

    Science.gov (United States)

    Rieppo, Lassi; Kokkonen, Harri T.; Kulmala, Katariina A. M.; Kovanen, Vuokko; Lammi, Mikko J.; Töyräs, Juha; Saarakkala, Simo

    2017-03-01

    Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.

  16. Vitamin D and Its Effects on Articular Cartilage and Osteoarthritis.

    Science.gov (United States)

    Garfinkel, Rachel J; Dilisio, Matthew F; Agrawal, Devendra K

    2017-06-01

    Osteoarthritis (OA) currently affects 10% of the American population. There has been a recent push to determine exactly what causes OA and how it can be treated most effectively. Serum vitamin D levels have been associated with OA and may have an effect on articular cartilage remodeling. To critically review the published research on the effect of vitamin D on articular cartilage and the development of OA as well as on the mechanism behind cartilage regeneration and degeneration. Review. A systematic search of PubMed and the Web of Science was performed for relevant studies published in the English language through April 30, 2016, using the terms vitamin D , articular cartilage , and osteoarthritis . On a molecular level, 1α,25(OH) 2 D 3 , the activated form of vitamin D, plays a role in articular cartilage degeneration. Vitamin D binds to vitamin D receptors, triggering a signaling cascade that leads to chondrocyte hypertrophy. In clinical trials, vitamin D deficiency poses a risk factor for OA, and those with decreased cartilage thickness are more likely to be vitamin D-insufficient. The role of vitamin D supplementation in the treatment or prevention of OA remains uncertain. More research is needed to reconcile these conflicting findings.

  17. Changes in articular cartilage after meniscectomy and meniscus replacement using a biodegradable porous polymer implant

    NARCIS (Netherlands)

    Hannink, G.J.; Tienen, T.G. van; Schouten, A.J.; Buma, P.

    2011-01-01

    PURPOSE: To evaluate the long-term effects of implantation of a biodegradable polymer meniscus implant on articular cartilage degeneration and compare this to articular cartilage degeneration after meniscectomy. METHODS: Porous polymer polycaprolacton-based polyurethane meniscus implants were

  18. Developmental Mechanisms in Articular Cartilage Degradation in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Elena V. Tchetina

    2011-01-01

    Full Text Available Osteoarthritis is the most common arthritic condition, which involves progressive degeneration of articular cartilage. The most recent accomplishments have significantly advanced our understanding on the mechanisms of the disease development and progression. The most intriguing is the growing evidence indicating that extracellular matrix destruction in osteoarthritic articular cartilage resembles that in the hypertrophic zone of fetal growth plate during endochondral ossification. This suggests common regulatory mechanisms of matrix degradation in OA and in the development and can provide new approaches for the treatment of the disease by targeting reparation of chondrocyte phenotype.

  19. Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface

    Science.gov (United States)

    Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Melvin, Gary M.; Manner, Paul A.

    2013-01-01

    Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner. Design: Impacts of increasing force are delivered to adult bovine articular cartilage explants in confined compression. Impact parameters are correlated with tissue damage, cell viability, matrix and inflammatory mediator release, and gene expression 24 hours postimpact. Results: Nitric oxide release is first detected after 7.7 MPa impacts, whereas cell death, glycosaminoglycan release, and prostaglandin E2 release are first detected at 17 MPa. Catabolic markers increase linearly to maximal levels after ≥36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. PMID:26069650

  20. Near Infrared Spectroscopic Mapping of Functional Properties of Equine Articular Cartilage

    NARCIS (Netherlands)

    Sarin, Jaakko K; Amissah, Michael; Brommer, Harold; Argüelles, David; Töyräs, Juha; Afara, Isaac O

    2016-01-01

    Mechanical properties of articular cartilage are vital for normal joint function, which can be severely compromised by injuries. Quantitative characterization of cartilage injuries, and evaluation of cartilage stiffness and thickness by means of conventional arthroscopy is poorly reproducible or

  1. Automatic quantification of local and global articular cartilage surface curvature

    DEFF Research Database (Denmark)

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F

    2008-01-01

    The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally. ...

  2. PRP and Articular Cartilage: A Clinical Update

    National Research Council Canada - National Science Library

    Marmotti, Antonio; Rossi, Roberto; Castoldi, Filippo; Roveda, Eliana; Michielon, Gianni; Peretti, Giuseppe M

    2015-01-01

      The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis...

  3. Hydrogels for the Repair of Articular Cartilage Defects

    Science.gov (United States)

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

    The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID:21510824

  4. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-07-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net /sup 35/SO/sub 4/-labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage.

  5. Strain-rate-dependent non-linear tensile properties of the superficial zone of articular cartilage.

    Science.gov (United States)

    Ahsanizadeh, Sahand; Li, LePing

    2015-11-01

    The tensile properties of articular cartilage play an important role in the compressive behavior and integrity of the tissue. The stress-strain relationship of cartilage in compression was observed previously to depend on the strain-rate. This strain-rate dependence has been thought to originate mainly from fluid pressurization. However, it was not clear to what extent the tensile properties of cartilage contribute to the strain-rate dependence in compressive behavior of cartilage. The aim of the present study was to quantify the strain-rate dependent stress-strain relationship and hysteresis of articular cartilage in tension. Uniaxial tensile tests were performed to examine the strain-rate dependent non-linear tensile properties of the superficial zone of bovine knee cartilage. Tensile specimens were oriented in the fiber direction indicated by the India ink method. Seven strain-rates were used in the measurement ranging from 0.1 to 80%/s, which corresponded to nearly static to impact joint loadings. The experimental data showed substantial strain-rate and strain-magnitude dependent load response: for a given strain-magnitude, the tensile stress could vary by a factor of 1.95 while the modulus by a factor of 1.58 with strain-rate; for a given strain-rate, the modulus at 15% strain could be over four times the initial modulus at no strain. The energy loss in cartilage tension upon unloading exhibited a complex variation with the strain-rate. The strain-rate dependence of cartilage in tension observed from the present study is relatively weaker than that in compression observed previously, but is considerable to contribute to the strain-rate dependent load response in compression.

  6. Articular cartilage repair and the evolving role of regenerative medicine

    Directory of Open Access Journals (Sweden)

    Pieter K Bos

    2010-10-01

    Full Text Available Pieter K Bos1, Marloes L van Melle1, Gerjo JVM van Osch1,21Department of Orthopaedic Surgery, Erasmus MC, Rotterdam, the Netherlands; 2Department of Otorhinolaryngology, Erasmus MC, Rotterdam, the NetherlandsAbstract: Among the growing applications of regenerative medicine, clinical articular cartilage repair has now been used for 2 decades and forms a successful example of translational medicine. Cartilage is characterized by a limited intrinsic repair capacity following injury. Articular cartilage defects cause symptoms, are not spontaneously repaired, and are generally believed to result in early osteoarthritis. Marrow stimulation techniques, osteochondral transplantation, and cell-based therapies, such as autologous chondrocyte implantation (ACI and use of mesenchymal stem cells (MSCs, are used for tissue regeneration, symptom relief, and prevention of further joint degeneration. The exact incidence of cartilage defects and the natural outcome of joints with these lesions are unclear. Currently available cartilage repair techniques are designed for defect treatment in otherwise healthy joints and limbs, mostly in young adults. The natural history studies presented in this review estimated that the prevalence of cartilage lesions in this patient group ranges from 5% to 11%. The background and results from currently available randomized clinical trials of the three mostly used cartilage repair techniques are outlined in this review. Osteochondral transplantation, marrow stimulation, and ACI show improvement of symptoms with an advantage for cell-based techniques, but only a suggestion that risk for joint degeneration can be reduced. MSCs, characterized by their good proliferative capacity and the potential to differentiate into different mesenchymal lineages, form an attractive alternative cell source for cartilage regeneration. Moreover, MSCs provide a regenerative microenvironment by the secretion of bioactive factors. This trophic activity

  7. Spatially resolved elemental distributions in articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Reinert, T. E-mail: reinert@physik.uni-leipzig.de; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gruender, W

    2001-07-01

    In this study, the nuclear microprobe technique is employed to analyse the chemistry of joint cartilage in order to correlate internal structures of the collagen network with the elemental distribution. The samples were taken from pig's knee joint. 30 {mu}m thick coronar cross-sections were prepared by means of cryosectioning and freeze-drying. We performed simultaneously particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and elastic recoil detection analysis (ERDA). Thus we obtained spatially resolved distributions of the elements H, C, N, O, P, S, Cl, K and Ca. The main components of the organic matrix are H, C, N and O. It was shown that their relations vary with the cartilage structures. It could be shown that zones with aligned collagen fibrils contain less sulphur and potassium but more chlorine. The higher chlorine concentration is remarkable because newest biochemical studies found that hypochloric acid is involved in cartilage degradation. Furthermore, the calcium distribution is still of great interest. Its correlation to structural changes inside the cartilage is still being discussed. It could be disproved that zones of higher calcium concentration are related to the aligned structures of the collagen network.

  8. Spatially resolved elemental distributions in articular cartilage

    Science.gov (United States)

    Reinert, T.; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gründer, W.

    2001-07-01

    In this study, the nuclear microprobe technique is employed to analyse the chemistry of joint cartilage in order to correlate internal structures of the collagen network with the elemental distribution. The samples were taken from pig's knee joint. 30 μm thick coronar cross-sections were prepared by means of cryosectioning and freeze-drying. We performed simultaneously particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and elastic recoil detection analysis (ERDA). Thus we obtained spatially resolved distributions of the elements H, C, N, O, P, S, Cl, K and Ca. The main components of the organic matrix are H, C, N and O. It was shown that their relations vary with the cartilage structures. It could be shown that zones with aligned collagen fibrils contain less sulphur and potassium but more chlorine. The higher chlorine concentration is remarkable because newest biochemical studies found that hypochloric acid is involved in cartilage degradation. Furthermore, the calcium distribution is still of great interest. Its correlation to structural changes inside the cartilage is still being discussed. It could be disproved that zones of higher calcium concentration are related to the aligned structures of the collagen network.

  9. Molecular modulation of articular cartilage degradation

    NARCIS (Netherlands)

    Landman, Ellie

    2013-01-01

    Cartilage homeostasis is maintained due to a balance between anabolic and catabolic processes, that are regulated by a complex network of signaling pathways. Disturbance of one or more of these pathways disrupts this balance, resulting in excessive breakdown of the extracellular matrix and

  10. Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?

    Directory of Open Access Journals (Sweden)

    A. R. Memon

    2012-01-01

    Full Text Available Articular cartilage (AC injury is a common disorder. Numerous techniques have been employed to repair or regenerate the cartilage defects with varying degrees of success. Three commonly performed techniques include bone marrow stimulation, cartilage repair, and cartilage regeneration. This paper focuses on current level of evidence paying particular attention to cartilage regeneration techniques.

  11. Biomechanical evaluation of suture holding properties of native and tissue engineered articular cartilage

    Science.gov (United States)

    DuRaine, GD; Arzi, B; Lee, JK; Lee, CA; Responte, DJ; Hu, JC; Athanasiou, KA

    2014-01-01

    Objective The purpose of this study was to determine suture-holding properties of tissue engineered neocartilage relative to native articular cartilage. To this end, suture pull-out strength was quantified for native articular cartilage and for neocartilages possessing various mechanical properties. Methods Suture holding properties were examined in vitro and in vivo. Neocartilage from bovine chondrocytes was engineered using two sets of exogenous stimuli resulting in neotissue of different biochemical compositions. Compressive and tensile properties and glycosaminoglycan, collagen, and pyridinoline cross-link contents were assayed (study 1). Suture pull-out strength was compared between neocartilage constructs, and bovine and leporine native cartilage. Uniaxial pull-out test until failure was performed after passing 6-0 Vicryl through each tissue (study 2). Subsequently, neocartilage was implanted into a rabbit model to examine short-term suture holding ability in vivo (study 3). Results Neocartilage glycosaminoglycan and collagen content per wet weight reached 4.55% ± 1.62% and 4.21 ± 0.77%, respectively. Tensile properties for neocartilage constructs reached 2.6 ± 0.77 MPa for Young’s modulus and 1.39 ± 0.63 MPa for ultimate tensile strength. Neocartilage reached ~33% of suture pull-out strength of native articular cartilage. Neocartilage cross-link content reached 50% of native values, and suture pull-out strength correlated positively with cross-link content (R2=0.74). Neocartilage sutured into rabbit osteochondral defects was successfully maintained for 3 weeks. Conclusion This study shows that pyridinoline cross-links in neocartilage may be vital in controlling suture pull-out strength. Neocartilage produced in vitro with one-third of native tissue pull-out strength appears sufficient for construct suturing and retention in vivo. PMID:24848644

  12. Segmenting articular cartilage automatically using a voxel classification approach

    DEFF Research Database (Denmark)

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F

    2007-01-01

    agreement with manual segmentations, an interscan reproducibility as good as that of a human expert, and enables the separation between healthy and osteoarthritic populations. While high-field scanners offer high-quality imaging from which the articular cartilage have been evaluated extensively using manual...... and automated image analysis techniques, low-field scanners on the other hand produce lower quality images but to a fraction of the cost of their high-field counterpart. For low-field MRI, there is no well-established accuracy validation for quantitative cartilage estimates, but we show that differences between...

  13. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics.

    Science.gov (United States)

    Łuczkiewicz, Piotr; Daszkiewicz, Karol; Chróścielewski, Jacek; Witkowski, Wojciech; Winklewski, Pawel J

    2016-01-01

    Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint.

  14. Advances in the Surgical Management of Articular Cartilage Defects

    OpenAIRE

    Stein, Spencer; Strauss, Eric; Bosco, Joseph

    2013-01-01

    Objective: The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process. Design: A PubMed search was performed using the phrase ?Autologous Chondrocyte Implantation? alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company we...

  15. Arthroscopic repair of delaminated acetabular articular cartilage in femoroacetabular impingement.

    Science.gov (United States)

    Sekiya, Jon K; Martin, RobRoy L; Lesniak, Bryson P

    2009-09-01

    Lesions to articular cartilage can be difficult to treat and directly impact surgical outcome in hip arthroscopy. This article describes a direct cartilage suture repair technique for a young, active individual with full-thickness acetabular cartilage delamination. Lesions of this type are commonly seen with femoroacetabular impingement. A 17-year-old boy presented with bilateral hip pain greater in the right than left. Arthroscopic intervention for the right hip included direct cartilage repair for the cartilage lesion, osteoplasty for femoroacetabular impingement, repair for an anterior labral tear, capsular plication for iliofemoral ligament laxity, and psoas lengthening. Twelve weeks postoperatively, a standard capsular plication, osteoplasty, and chondroplasty were performed on the left hip. At follow-up, the patient reported feeling 95% normal. He noted that the right and left hips were essentially the same. Symptoms consisted of stiffness after prolonged sitting and mild pain following sports. The patient reported being pain free 90% of the time, with pain 2/10 at worst. He scored a 96 on the modified Harris Hip Score, 93 on the Hip Outcome Score Activities of Daily Living subscale, and 81 on the Hip Outcome Score Sports subscale. Overall, the patient was satisfied with the outcome. The direct cartilage repair, in addition to osteoplasty, anterior superior labral repair, iliofemoral capsular plication, and psoas lengthening, produced an excellent outcome in this young, active patient.

  16. Theory of the short time mechanical relaxation in articular cartilage.

    Science.gov (United States)

    Ruberti, J W; Sokoloff, J B

    2011-10-01

    Articular cartilage is comprised of macromolecules, proteoglycans, with (charged) chondroitin sulfate side-chains attached to them. The proteoglycans are attached to longer hyaluronic acid chains, trapped within a network of type II collagen fibrils. As a consequence of their relatively long persistence lengths, the number of persistence lengths along the chondroitin sulfate and proteoglycan chains is relatively small, and consequently, the retraction times for these side chains are also quite short. We argue that, as a consequence of this, they will not significantly inhibit the reptation of the hyaluronic acid chains. Scaling arguments applied to this model allow us to show that the shortest of the mechanical relaxation times of cartilage, that have been determined by Fyhrie and Barone to be due to reptation of the hyaluronic acid polymers, should have a dependence on the load, i.e., force per unit interface area P, carried by the cartilage, proportional to P(3/2).

  17. Osteoprotegerin deficiency leads to deformation of the articular cartilage in femoral head.

    Science.gov (United States)

    Liu, Yi; Ge, Jianping; Chen, Danying; Weng, Yuteng; Du, Haiming; Sun, Yao; Zhang, Qi

    2016-10-01

    Osteoarthritis (OA) was a degenerative joint disease characterized by articular cartilage degradation and extensive remodeling of the subchondral bone. Multiple lines of evidence indicated that Osteoprotegerin (OPG), a member of TNF receptor superfamily that was expressed in the chondrocytes of articular cartilage and adjacent locations in the physiological setting, was involved in maintaining integrity of articular cartilage. OPG could prevent subchondral bone from resorption, and also protect cartilage from degradation. In this study, we used Osteoprotegerin-knockout mice (Opg-KO mice) to find out the role of OPG in articular cartilage. We examined articular cartilage in the femoral head of Opg-KO mice began in early adulthood using modern molecular and imaging methods. We found cartilage changes starting from adulthood and progressively with age, reminiscent of pathological changes in OA. Deficiency of OPG caused thinned articular cartilage and extensive remodeling of the subchondral bone in femoral head in comparison with wild-type mice (WT mice). Also, the articular cartilage of femoral head expressed significantly less of Aggrecan, Col-II and Col-X, but more Col-I and Matrix Metalloproteinases-13 (Mmp-13) than WT mice both at gene and protein level. Moreover, increased chondrocyte apoptosis and decreased chondrocyte proliferation were observed in femoral head of Opg-KO mice compared to WT mice. These data suggested that OPG played an important role in maintaining the homeostasis of articular cartilage of femoral head.

  18. Zn deposition at the bone-cartilage interface in equine articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, D.A. [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom)], E-mail: D.A.Bradley@surrey.ac.uk; Moger, C.J.; Winlove, C.P. [School of Physics, University of Exeter, Exeter, EX4 4QL (United Kingdom)

    2007-09-21

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 {mu}m and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  19. Articular cartilage thickness measured with US is not as easy as it appears

    DEFF Research Database (Denmark)

    Torp-Pedersen, S; Bartels, E M; Wilhjelm, Jens E.

    2011-01-01

    Theoretically, the high spatial resolution of US makes it well suited to monitor the decrease in articular cartilage thickness in osteoarthritis. A requirement is, however, that the borders of the cartilage are correctly identified and that the cartilage is measured under orthogonal insonation....... If US measurements are compared to measurements with other techniques, they should be corrected for the higher sound speed in cartilage....

  20. Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

    2017-04-01

    Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

  1. Autologous cartilage implantation for full thickness articular cartilage defects of the knee.

    Science.gov (United States)

    Wasiak, J; Villanueva, E

    2002-01-01

    A variety of strategies have been employed for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty. These treatments are not always effective and when they are, the benefits may only be transitory. Unsuccessfully treated cartilage damage may progress to degenerative disease states and result in the need for a total knee replacement. In recent years the surgical implantation of healthy cartilage cells (autologous cartilage implantation [ACI] ) into damaged areas has been seen as an alternative option and is currently under investigation as a potential improvement over the current strategies for the management and treatment of articular cartilage defects. To determine the effectiveness of ACI in patients with full thickness articular cartilage defects of the knee. We searched the Cochrane Musculoskeletal Injuries Group specialised register (May 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to June Week 4 2001), CINAHL (1982 to July Week 2 2001), EMBASE (1980 to 2001 Week 27), SPORTDiscus (1949 to June 2001), Current Contents (1993 Week 26 to 2001 Week 30) and the National Research Register (Issue 2, May 2002). Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, trochlea or patella. Two independent reviewers applied the entry criteria to identified studies. No completed randomised controlled trials investigating this treatment were identified through the above searches. One possible trial has been placed in Studies Awaiting Assessment, awaiting translation of the full trial report. Ongoing trials currently underway will be incorporated in future updates of this review. No information is available from RCTs which can influence current practice. Therefore, since current evidence is subject to the inherent weaknesses of case series or

  2. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    Science.gov (United States)

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    The articular cartilage is a well-organized tissue for smooth and friction-free joint movement for locomotion in animals and humans. Adult articular cartilage has a very low self-regeneration capacity due to its avascular nature. The regeneration of articular cartilage surface is critical to prevent the progression to osteoarthritis (OA). Although various joint resurfacing procedures in experimental articular cartilage defects have been developed, no standardized clinical protocol has yet been established. The three critical ingredients for tissue regeneration are morphogens and growth factors, cells, and scaffolds. The concepts based on the regeneration triad have been extensively investigated in animal models. However, these studies in animal models have demonstrated variable results and outcomes. An optimal animal model must precisely mimic and model the sequence of events in articular cartilage regeneration in human. In this article, the progress and remaining challenges in articular cartilage regeneration in animal models are reviewed. The role of individual morphogens and growth factors in cartilage regeneration has been investigated. In normal articular cartilage homeostasis, morphogens and growth factors function sequentially in tissue regeneration. Mesenchymal stem cell-based repair of articular cartilage defects, performed with or without various growth factors and scaffolds, has been widely attempted in animal models. Stem cells, including embryonic and adult stem cells and induced pluripotent stem cells, have also been reported as attractive cell sources for articular cartilage surface regeneration. Several studies with regard to scaffolds have been advanced, including recent investigations based on nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds, and extracellular matrix scaffolds for articular cartilage surface regeneration. Continuous refinement of animal models in chondral and osteochondral defects provide opportunities

  3. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics.

    Directory of Open Access Journals (Sweden)

    Piotr Łuczkiewicz

    Full Text Available Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis.The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas.In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model.We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint.

  4. A study of crystalline biomaterials for articular cartilage bioengineering

    Energy Technology Data Exchange (ETDEWEB)

    Gross-Aviv, Talia [Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, 84105 (Israel)], E-mail: taliag@bgu.ac.il; DiCarlo, Bryan B. [Department of Bioengineering, Rice University, Houston, TX 77003 (United States)], E-mail: bdicarlo@rice.edu; French, Margaret M. [Department of Bioengineering, Rice University, Houston, TX 77003 (United States)], E-mail: mmfrench@rice.edu; Athanasiou, Kyriacos A. [Department of Bioengineering, Rice University, Houston, TX 77003 (United States)], E-mail: athanasiou@rice.edu; Vago, Razi [Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, 84105 (Israel)], E-mail: rvago@bgu.ac.il

    2008-12-01

    This study examines the suitability of marine origin coral species, Porites lutea (POR) and the hydrozoan Millepora dichotoma (MIL), for use as novel three dimensional growth matrices in the field of articular cartilage tissue engineering. Therefore, mesenchymal stem cells (MSCs) and chondrocytes were grown on the skeletal material obtained from each of these two organisms to investigate their potential use as three dimensional scaffolding for cartilage tissue growth. Chondrogenic induction of MSCs was achieved by addition of transforming growth factor-{beta}1 (TGF-{beta}1) and insulin growth factor-I (IGF-I). Cell adherence, proliferation, differentiation and tissue development were investigated through six weeks of culture. Cartilage tissue growth and chondrocytic phenotype maintenance of each cell type were examined by cell morphology, histochemical analyses, expression of collagen type II and quantitative measures of glycosaminoglycan (GAG) content. The MSCs and the chondrocytes were shown good adherence to the scaffolds and maintenance of the chondrocytic phenotype in the initial stages of culture. However after two weeks of culture on MIL and three weeks on POR these cultures began to exhibit signs of further differentiation and phenotypic loss. The shown results indicated that POR was a better substrate for chondrocytes phenotype maintenance than MIL. We believe that surface modification of POR combined with mechanical stimuli will provide a suitable environment for chondrogenic phenotype maintenance. Further investigation of POR and other novel coralline biomatrices is indicated and warranted in the field of cartilage tissue engineering applications.

  5. Experimentally induced cartilage degeneration treated by pulsed electromagnetic field stimulation; an in vitro study on bovine cartilage.

    Science.gov (United States)

    Veronesi, Francesca; Fini, Milena; Giavaresi, Gianluca; Ongaro, Alessia; De Mattei, Monica; Pellati, Agnese; Setti, Stefania; Tschon, Matilde

    2015-10-20

    Osteoarthritis (OA) is the final result of progressive alterations to articular cartilage structure, composition and cellularity, followed by an increase in the concentration of pro-inflammatory cytokines in joint synovial fluid. Even though the effect of pulsed electromagnetic field (PEMF) stimulation in counteracting OA progression and inflammation is of increasing interest, because of its anabolic and anti-inflammatory properties, the present study aimed to improve the knowledge on cartilage extracellular matrix (ECM) and chondrocyte changes related to the exposure of PEMF, from a histological and histomorphometric point of view. An in vitro OA model was realized, culturing bovine cartilage explants with a high dose of interleukin 1β (IL1β, 50 ng/ml) at different experimental times (24 h, and 7 and 21 days). The effects of PEMFs (75 Hz, 1.5 mT) were evaluated in cartilage explants treated with IL1β or not (control), in terms of cartilage structure, cellularity and proteoglycans, glycosaminoglycans, collagen II and transforming growth factor β1 synthesis by using histology, histomorphometry and immunohistochemistry. Making a comparison with control cartilage, IL1β-treated explants showed a decrease in cartilage matrix, structure and cellularity parameters. PEMFs were able to counteract the progression of OA acting on both cartilage cellularity and ECM in cartilage previously treated with IL1β. Normal distribution (Kolmogroc-Smirnov test) and homoscedasticity (Levene test) of data were verified, then, the non-parametric Kruskal Wallis test followed by Mann-Whiteny U test for pairwise comparisons were performed. The p-value was adjusted according to the Dunn-Sidak correction. These results, obtained by culturing and treating cartilage explants from two different joints, confirmed that PEMF stimulation can be used as adjuvant therapy to preserve cartilage from detrimental effects of high inflammatory cytokine levels during OA.

  6. Mechanical characterization of articular cartilage by combining magnetic resonance imaging and finite-element analysis-a potential functional imaging technique

    Energy Technology Data Exchange (ETDEWEB)

    Julkunen, P; Korhonen, R K; Nissi, M J; Jurvelin, J S [Department of Physics, University of Kuopio, PO Box 1627, FI-70211 Kuopio (Finland)], E-mail: petro.julkunen@uku.fi

    2008-05-07

    Magnetic resonance imaging (MRI) provides a method for non-invasive characterization of cartilage composition and structure. We aimed to see whether T{sub 1} and T{sub 2} relaxation times are related to proteoglycan (PG) and collagen-specific mechanical properties of articular cartilage. Specifically, we analyzed whether variations in the depthwise collagen orientation, as assessed by the laminae obtained from T{sub 2} profiles, affect the mechanical characteristics of cartilage. After MRI and unconfined compression tests of human and bovine patellar cartilage samples, fibril-reinforced poroviscoelastic finite-element models (FEM), with depthwise collagen orientations implemented from quantitative T{sub 2} maps (3 laminae for human, 3-7 laminae for bovine), were constructed to analyze the non-fibrillar matrix modulus (PG specific), fibril modulus (collagen specific) and permeability of the samples. In bovine cartilage, the non-fibrillar matrix modulus (R = -0.64, p < 0.05) as well as the initial permeability (R = 0.70, p < 0.05) correlated with T{sub 1}. In bovine cartilage, T{sub 2} correlated positively with the initial fibril modulus (R = 0.62, p = 0.05). In human cartilage, the initial fibril modulus correlated negatively (R = -0.61, p < 0.05) with T{sub 2}. Based on the simulations, cartilage with a complex collagen architecture (5 or 7 laminae), leading to high bulk T{sub 2} due to magic angle effects, provided higher compressive stiffness than tissue with a simple collagen architecture (3 laminae). Our results suggest that T{sub 1} reflects PG-specific mechanical properties of cartilage. High T{sub 2} is characteristic to soft cartilage with a classical collagen architecture. Contradictorily, high bulk T{sub 2} can also be found in stiff cartilage with a multilaminar collagen fibril network. By emerging MRI and FEM, the present study establishes a step toward functional imaging of articular cartilage.

  7. Influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage

    NARCIS (Netherlands)

    Brama, P.A.J.; TeKoppele, J.M.; Bank, R.A.; Weeren, P.R. van; Barneveld, A.

    1999-01-01

    Objective - To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. Sample Population - Articular cartilage specimens from 53 horses 4 to 30 years old. Procedure - Healthy

  8. Changes in articular cartilage after meniscectomy and meniscus replacement using a biodegradable porous polymer implant

    NARCIS (Netherlands)

    Hannink, Gerjon; van Tienen, Tony G.; Schouten, Arend Jan; Buma, Pieter

    To evaluate the long-term effects of implantation of a biodegradable polymer meniscus implant on articular cartilage degeneration and compare this to articular cartilage degeneration after meniscectomy. Porous polymer polycaprolacton-based polyurethane meniscus implants were implanted for 6 or 24

  9. Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation.

    Science.gov (United States)

    Sondergaard, B C; Henriksen, K; Wulf, H; Oestergaard, S; Schurigt, U; Bräuer, R; Danielsen, I; Christiansen, C; Qvist, P; Karsdal, M A

    2006-08-01

    Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models. Bovine articular cartilage explants were stimulated with oncostatin M (OSM) 10 ng/ml and tumor necrosis factor-alpha (TNF-alpha) 20 ng/ml in the presence or absence of the broad-spectrum MMP inhibitor GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was evaluated in the conditioned medium by glycosaminoglycans (GAG), hydroxyproline, and cross-linked C-telopeptide fragments of type II collagen (CTX-II), which were compared to immunohistochemical evaluations of proteoglycans and CTX-II. We assessed MMP expression by gelatine zymography and CK expression by immunohistochemistry. In vivo, CTX-II release was measured from CK-deficient mice. OSM and TNF-alpha combined induced significant (Pdegradation products measured by hydroxyproline and CTX-II compared to vehicle control. The cytokines potently induced MMP expression, assessed by zymography, and CK expression investigated by immunohistochemistry. Inhibition of MMP activity completely abrogated hydroxyproline and CTX-II release (Pdegradation. In contrast, inhibition of cysteine proteases resulted in an increase rather than a decrease in MMP derived fragments of collagen type II degradation, CTX-II, suggesting altered collagen metabolism.

  10. Characterization of Articular Cartilage Recovery and Its Correlation with Optical Response in the Near-Infrared Spectral Range.

    Science.gov (United States)

    Afara, Isaac Oluwaseun; Singh, Sanjleena; Moody, Hayley; Zhang, Lihai; Oloyede, Adekunle

    2017-07-01

    In this study, we examine the capacity of a new parameter, based on the recovery response of articular cartilage, to distinguish between healthy and damaged tissues. We also investigate whether or not this new parameter correlates with the near-infrared (NIR) optical response of articular cartilage. Normal and artificially degenerated (proteoglycan-depleted) bovine cartilage samples were nondestructively probed using NIR spectroscopy. Subsequently they were subjected to a load and unloading protocol, and the recovery response was logged during unloading. The recovery parameter, elastic rebound ( ER), is based on the strain energy released as the samples underwent instantaneous elastic recovery. Our results reveal positive relationship between the rebound parameter and cartilage proteoglycan content (normal samples: 2.20 ± 0.10 N mm; proteoglycan-depleted samples: 0.50 ± 0.04 N mm for 1 hour of enzymatic treatment and 0.13 ± 0.02 N mm for 4 hours of enzymatic treatment). In addition, multivariate analysis using partial least squares regression was employed to investigate the relationship between ER and NIR spectral data. The results reveal significantly high correlation ( R(2)cal = 98.35% and R(2)val = 79.87%; P cartilage in the combined NIR regions 5,450 to 6,100 cm(-1) and 7,500 to 12,500 cm(-1). We conclude that ER can indicate the mechanical condition and state of health of articular cartilage. The correlation of ER with cartilage optical response in the NIR range could facilitate real-time evaluation of the tissue's integrity during arthroscopic surgery and could also provide an important tool for cartilage assessment in tissue engineering and regeneration research.

  11. Black Colouration of the Knee Articular Cartilage after Spontaneously Recurrent Haemarthrosis

    Directory of Open Access Journals (Sweden)

    Kazu Matsumoto

    2016-01-01

    Full Text Available Mild discolouration of the articular cartilage is known to gradually occur during aging. However, pathological tissue pigmentation is occasionally induced under several specific conditions. In the present case, we performed total knee replacement in a patient with recurrent haemarthrosis. However, during the operation, we observed severe black colouration of the knee articular cartilage, due to the deposition of hemosiderin and lipofuscin. To our knowledge, this is the first report of severe cartilage pigmentation, due to hemosiderin and lipofuscin deposition in articular cartilage.

  12. The influence of collagen network integrity on the accumulation of gadolinium-based MR contrast agents in articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Wiener, Edzard; Schmidt, C.; Diederichs, G. [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie; Settles, M. [Klinikum rechts der Isar, Muenchen (Germany). Inst. fuer Roentgendiagnostik; Weirich, G. [Klinikum Rechts der Isar, Muenchen (Germany). Inst. fuer Pathologie und Pathologische Anatomie

    2011-03-15

    Delayed gadolinium-enhanced MR imaging of cartilage is used to quantify the proteoglycan loss in early osteoarthritis. It is assumed that T 1 after Gd-DTPA administration in the near equilibrium state reflects selective proteoglycan loss from cartilage. To investigate the influence of the collagen network integrity on contrast accumulation, the relaxation rates {delta}R1 and {delta}R2 were compared after Gd-DTPA administration in a well established model of osteoarthritis. Collagen or proteoglycan depletion was induced by the proteolytic enzymes papain and collagenase in healthy bovine patellar cartilage. Using a dedicated MRI sequence, T{sub 1} and T{sub 2} maps were simultaneously acquired before and 11 h after Gd-DTPA administration. Depth-dependent profiles of {delta}R1 and {delta}R2 were calculated in healthy, proteoglycan and collagen-depleted articular cartilage and the mean values of different cartilage layers were compared using the Mann-Whitney-U test. In superficial layers (1 mm) there was no significant difference (p > 0.05) in either {delta}R1 or {delta}R2 between proteoglycan-depleted (16.6 {+-} 1.2 s{sup -1}, 15.9 {+-} 1.0 s{sup -1}) and collagen-depleted articular cartilage (15.3 {+-} 0.9 s{sup -1}, 15.5 {+-} 0.9 s{sup -1}). In deep layers (3 mm) both parameters were significantly higher (p = 0.005, 0.03) in proteoglycan-depleted articular cartilage (12.3 {+-} 1.1 s{sup -1}, 9.8 {+-} 0.8 s{sup -1}) than in collagen-depleted articular cartilage (9.1 {+-} 1.1 s{sup -1}, 8.7 {+-} 0.7 s{sup -1}). Both proteoglycan loss and alterations in the collagen network influence the accumulation of Gd-DTPA in articular cartilage with significant differences between superficial and deep cartilage layers. (orig.)

  13. Evaluation of influence of proteoglycans on hydration of articular cartilage with the use of ultrasound

    Directory of Open Access Journals (Sweden)

    Yi-yi YANG

    2015-04-01

    Full Text Available Objective To monitor the changes in hydration behaviour of articular cartilage induced by degradation of proteoglycans, and to explore the effect of proteoglycans on hydration behaviour of articular cartilage by using high-frequency ultrasound. Methods Twelve porcine patellae with smooth cartilage surface were prepared and equally divided into two groups: normal group without any enzyme treatment, and trypsin group they were treated with 0.25% trypsin for 8h to digest proteoglycan in the cartilage. The hydration behaviour of the cartilage tissue was scanned by high-frequency ultrasound system with a central frequency of 25MHz. Parameters including cartilage hydration strain and cartilage thickness were measured. The histopathological changes in the articular cartilage were observed under a light microscope. Results It took approximately 20min to reach equilibrium during the hydration process in the normal cartilages, while proteoglycan-degraded cartilage took only about 5min to achieve equilibrium. The equilibrium strain of normal cartilage was 3.5%±0.5%. The degradation of proteoglycans induced a significant decrease in equilibrium strain (1.8%±0.2%, P0.05. Conclusion Proteoglycans play an important role in hydration behaviour of articular cartilage. The degradation of proteoglycans could induce degeneration of cartilage structure and decrease in hydration behaviour after dehydration. DOI: 10.11855/j.issn.0577-7402.2015.03.03

  14. Label-free characterization of articular cartilage in osteoarthritis model mice by Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

    2017-02-01

    Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this study, we generated an animal OA model surgically induced by knee joint instability, and the femurs were harvested at two weeks after the surgery. We performed Raman spectroscopic analysis for the articular cartilage of distal femurs in OA side and unaffected side in each mouse. In the result, there is no gross findings in the surface of the articular cartilage in OA. On the other hand, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The major finding of this study is that the relative intensity of phosphate band (960 cm-1) increases in the degenerative cartilage. This may be the result of exposure of subchondral bone due to thinning of the cartilage layer. In conclusion, Raman spectroscopic technique is sufficient to characterize articular cartilage in OA as a pilot study for Raman application in cartilage degeneration and regeneration using animal models and human subjects.

  15. Ultrasound elastomicroscopy for articular cartilage: from static to transient and 1D to 2D

    Science.gov (United States)

    Zheng, Yongping; Bridal, Sharon L.; Shi, Jun; Saied, Amena; Lu, Minghua; Jaffre, Britta; Mak, Arthur F. T.; Laugier, Pascal; Qin, Ling

    2003-05-01

    Articular cartilage (AC) is a biological weight-bearing tissue covering the ends of articulating bones within synovial joints. Its function very much depends on the unique multi-layered structure and the depth-dependent material properties, which have not been well invetigated nondestructively. In this study, transient depth-dependent material properties of bovine patella cartilage were measured using ultrasound elastomicroscopy methods. A 50 MHz focused ultrasound transducer was used to collect A-mode ultrasound echoes from the articular cartilage during the compression and subsequent force-relaxation. The transient displacements of the cartilage tissues at different depths were calculated from the ultrasound echoes using a cross-correlation technique. It was observed that the strains in the superficial zone were much larger than those in the middle and deep zones as the equilibrium state was approached. The tissues inside the AC layer continued to move during the force-relaxation phase after the compression was completed. This process has been predicted by a biphasic theory. In this study, it has been verified experimentally. It was also observed that the tissue deformations at different depths of AC were much more evenly distributed before force-relaxation. AC specimens were also investigated using a 2D ultrasound elastomicroscopy system that included a 3D translating system for moving the ultrasound transducer over the specimens. B-mode RF ultrasound signals were collected from the specimens under different loading levels applied with a specially designed compressor. Preliminary results demonstrated that the scanning was repeatable with high correlation of radio frequency signals obtained from the same site during different scans when compression level was unchanged (R2 > 0.97). Strains of the AC specimens were mapped using data collected with this ultrasound elastomicroscope. This system can also be potentially used for the assessment of other biological

  16. Genesis and morphogenesis of limb synovial joints and articular cartilage.

    Science.gov (United States)

    Decker, Rebekah S; Koyama, Eiki; Pacifici, Maurizio

    2014-10-01

    Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Together, these tissues give each joint its unique shape, organization and biomechanical function. Articular cartilage itself is rather complex and organized in distinct zones, including the superficial zone that produces lubricants and contains stem/progenitor cells. For many years there has been great interest in deciphering the mechanisms by which the joints form and come to acquire such unique structural features and diversity. Decades ago, classic embryologists discovered that the first overt sign of joint formation at each prescribed limb site was the appearance of a dense and compact population of mesenchymal cells collectively called the interzone. Work carried out since then by several groups has provided evidence that the interzone cells actively participate in joint tissue formation over developmental time. This minireview provides a succinct but comprehensive description of the many important recent advances in this field of research. These include studies using various conditional reporter mice to genetically trace and track the origin, fate and possible function of joint progenitor cells; studies on the involvement and roles in signaling pathways and transcription factors in joint cell determination and functioning; and studies using advanced methods of gene expression analyses to uncover novel genetic determinants of joint formation and diversity. The overall advances are impressive, and the findings are not only of obvious interest and importance but also have major implications in the conception of future translational medicine tools to repair and regenerate defective, overused or aging joints. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  17. Tribology approach to the engineering and study of articular cartilage.

    Science.gov (United States)

    Wimmer, Markus A; Grad, Sibylle; Kaup, Thomas; Hänni, Markus; Schneider, Erich; Gogolewski, Sylwester; Alini, Mauro

    2004-01-01

    This study has been based on the assumption that articular motion is an important aspect of mechanotransduction in synovial joints. For this reason a new bioreactor concept, able to reproduce joint kinematics more closely, has been designed. The prototype consists of a rotating scaffold and/or cartilage pin, which is pressed onto an orthogonally rotating ball. By oscillating pin and ball in phase difference, elliptical displacement trajectories are generated that are similar to the motion paths occurring in vivo. Simultaneously, dynamic compression may be applied with a linear actuator, while two-step-motors generate the rotation of pin and ball. The whole apparatus is placed in an incubator. The control station is located outside. Preliminary investigations at the gene expression level demonstrated promising results. Compared with free-swelling control and/or simply compression-loaded samples, chondrocyte-seeded scaffolds as well as nasal cartilage explants exposed to interface motion both showed elevated levels of cartilage oligomeric matrix protein mRNA. The final design of the bioreactor will include four individual stations in line, which will facilitate the investigation of motion-initiated effects at the contacting surfaces in more detail.

  18. Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

    Science.gov (United States)

    Raya, José G.

    2014-01-01

    Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

  19. Articular Cartilage Thickness Measured with US is Not as Easy as It Appears

    DEFF Research Database (Denmark)

    Torp-Pedersen, Søren; Bartels, E. M.; Wilhjelm, Jens E.

    2011-01-01

    Background: Theoretically, the high spatial resolution of US makes it well suited to monitor the decrease in articular cartilage thickness in osteoarthritis. A requirement is, however, that the borders of the cartilage are correctly identified and that the cartilage ismeasured under orthogonal in...

  20. Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation

    DEFF Research Database (Denmark)

    Karsdal, Morten Asser; Sumer, Eren Ufuk; Wulf, Helle

    2007-01-01

    -dependently inhibited by forskolin and IBMX. The highest concentration of IBMX lowered cytokine-induced release of sGAG by 72%. CONCLUSION: Levels of cAMP in chondrocytes play a key role in controlling catabolic activity. Increased cAMP levels in chondrocytes inhibited MMP expression and activity and consequently......OBJECTIVE: Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective. METHODS: Cartilage degradation...... was induced in bovine articular cartilage explants by 10 ng/ml oncostatin M (OSM) and 20 ng/ml tumor necrosis factor (TNF). In these cultures, cAMP levels were augmented by treatment with either forskolin (4, 16, or 64 microM) or 3-isobutyl-1-methyl xanthine (IBMX; 4, 16, or 64 microM). Cartilage degradation...

  1. Deginerative changes of femoral articular cartilage in the knee : comparative study of specimen sonography and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Youn; Hong, Sung Hwan; Sohn, Jin Hee; Wee, Young Hoon; Chang, Jun Dong; Park, Hong Seok; Lee, Eil Seoung; Kang Ik Won [Hallym Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-04-01

    To determine the sonographic findings of degenerative change in femoral articular cartilage of the knee by comparative study of specimen sonography and pathology. We obtained 40 specimens of cartilage of the femur (20 medial and 20 lateral condylar) from 20 patients with osteoarthritis of the knee who had undergone total knee replacement. The specimens were placed in a saline-filled container and sonography was performed using a 10-MHz linear transducer. Sonographic abnormalities were evaluated at the cartilage surface, within the cartilage, and at the bone-cartilage interface, and were compared with the corresponding pathologic findings. In addition, cartilage thickness was measured at a representative portion of each femoral cartilage specimen and was compared with the thickness determined by sonography. 'Dot' lesions, irregularity or loss of the hyperechoic line, were demonstrated by sonography at the saline-cartilage interface of 14 cartilages. Pathologic examination showed that these findings corresponded to cleft, detachment, erosion, and degeneration. Irregularities in the hyperechoic line at the bone-cartilage interface were revealed by sonography in eight cartilages and were related to irregularity or loss of tidemark, downward displacement of the cartilage, and subchondral callus formation. Dot lesions, corresponding to cleft and degeneration, were noted within one cartilage. Cartilage thickness measured on specimen and by sonography showed no significant difference (p=0.446). Specimen sonography suggested that articular cartilage underwent degenerative histopathological change. Cartilage thickness measured by sonography exactly reflected real thickness.

  2. The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants

    DEFF Research Database (Denmark)

    He, Yi; Zheng, Qinlong; Jiang, Mengmeng

    2015-01-01

    Objective The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative...... contribution of ADAMTS-4 and ADAMTS-5 to cartilage degradation upon catabolic stimulation; ii) To investigate the effect of regulating the activities of key enzymes by mean of broad-spectrum inhibitors. Methods Bovine full-depth cartilage explants stimulated with tumor necrosis factor alpha (TNF...... protease for the generation of 374ARGS aggrecan fragment in the TNF-α/OSM stimulated bovine cartilage explants. This study addresses the need to determine the roles of ADAMTS-4 and ADAMTS-5 in human articular degradation in OA and hence identify the attractive target for slowing down human cartilage...

  3. Contact mechanics of articular cartilage layers asymptotic models

    CERN Document Server

    Argatov, Ivan

    2015-01-01

    This book presents a comprehensive and unifying approach to articular contact mechanics with an emphasis on frictionless contact interaction of thin cartilage layers. The first part of the book (Chapters 1–4) reviews the results of asymptotic analysis of the deformational behavior of thin elastic and viscoelastic layers. A comprehensive review of the literature is combined with the authors’ original contributions. The compressible and incompressible cases are treated separately with a focus on exact solutions for asymptotic models of frictionless contact for thin transversely isotropic layers bonded to rigid substrates shaped like elliptic paraboloids. The second part (Chapters 5, 6, and 7) deals with the non-axisymmetric contact of thin transversely isotropic biphasic layers and presents the asymptotic modelling methodology for tibio-femoral contact. The third part of the book consists of Chapter 8, which covers contact problems for thin bonded inhomogeneous transversely isotropic elastic layers, and Cha...

  4. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke

    2015-01-01

    BACKGROUND: A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. Ideally, the animal model should allow for testing of clinically relevant...... repair techniques and evaluating the use of two defects per knee. METHODS: Sixteen fully mature Göttingen minipigs were used. The minipigs received bilateral trochlear osteochondral drill-hole defects or chondral defects (Ø 6 mm), either one defect per knee or two defects per knee. The defects were...... minipig model was easy to handle, cost-effective and provided predictable outcome. Based on this study the use of two defects per knee, one in the medial and one in the lateral trochlear facet, in male Göttingen minipigs is recommended....

  5. Effects of intra articular tramadol on articular cartilage and synovium of rats

    Directory of Open Access Journals (Sweden)

    Musa Kola

    2015-12-01

    Full Text Available Objective: To investigate the effects of intra articular tramadol injection on articular cartilage and synovium in rat knee joint. Methods: After Animal Ethical Committee approval, a total of 20 Sprague-Dawley rats were used and divided into 4 groups. Each group was composed of 5 rats. 0.2 ml of tramadol HCl was injected into the right knee joints and left knee joints of all the rats were considered as control. Control side joints received saline injection. Rats were sacrificed with ketamin on 1st, 7th, 14th and 21st days and knee joints were removed. Obtained tissue samples were decalcified and were dyed with Hematoxylin-eosin and Masson’s trichrome stain and examined by light microscopy for the presence of inflammation in periarticular area and synovia. Results: Congestion of synovial veins and perivascular cell infiltration were observed in tramadol group on days 1 and 7 (P < 0.05. The inflammation process was replaced by fibrosis on day 14 and fibrosis was significantly decreased on day 21. Conclusion: Intra articular tramadol should be used cautiously, keeping in mind that it may cause synovial inflammation in early phases and fibrosis in late phases. J Clin Exp Invest 2015; 6 (4: 337-342

  6. Cartilage (Bovine and Shark) (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about the use of bovine and shark cartilage as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  7. Cartilage (Bovine and Shark) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the use of bovine and shark cartilage as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  8. Patellar articular cartilage lesions: in vitro MR imaging evaluation after placement in gadopentetate dimeglumine solution.

    Science.gov (United States)

    Woertler, Klaus; Buerger, Horst; Moeller, Jens; Rummeny, Ernst J

    2004-03-01

    To evaluate T1-weighted magnetic resonance (MR) imaging after diffusion of gadopentetate dimeglumine for visualization of articular cartilage lesions. MR imaging was performed in eight human cadaveric patella specimens immediately and 4 hours after placement into a vessel filled with gadopentetate dimeglumine solution (2.5 mmol/L). T1-weighted spin-echo and inversion-recovery turbo spin-echo MR sequences with nulled cartilage signal (inversion time of 300 msec) were used. In a total of 128 articular cartilage areas, MR imaging findings were compared with macroscopic and histopathologic findings. Pathologic evaluation was performed by one musculoskeletal pathologist. With knowledge of pathologic observations, MR images were analyzed by one musculoskeletal radiologist with regard to intrinsic signal intensity characteristics and surface abnormalities of articular cartilage. Histopathologic findings demonstrated 67 areas of normal articular cartilage and 66 cartilage lesions (grade 1, n = 19; grade 2, n = 15; grade 3, n = 26; grade 4, n = 6). All grade 3 and 4 lesions could be identified on MR images obtained immediately after submersion and after 4 hours. Ninety-four percent of grade 1 and 2 lesions were identified as areas of predominantly decreased contrast enhancement on delayed MR images obtained with both sequences. MR images obtained immediately after submersion demonstrated abnormal signal intensity in only 9% and 12% of grade 1 and 2 lesions, respectively. T1-weighted MR images obtained in vitro after gadopentetate dimeglumine diffusion allow demonstration of articular cartilage surface lesions and early stages of cartilage degradation. Copyright RSNA, 2004

  9. Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

    Science.gov (United States)

    Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

    2017-06-01

    Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

  10. Correlation between apparent diffusion coefficient and viscoelasticity of articular cartilage in a porcine model.

    Science.gov (United States)

    Aoki, T; Watanabe, A; Nitta, N; Numano, T; Fukushi, M; Niitsu, M

    2012-09-01

    Quantitative MR imaging techniques of degenerative cartilage have been reported as useful indicators of degenerative changes in cartilage extracellular matrix, which consists of proteoglycans, collagen, non-collagenous proteins, and water. Apparent diffusion coefficient (ADC) mapping of cartilage has been shown to correlate mainly with the water content of the cartilage. As the water content of the cartilage in turn correlates with its viscoelasticity, which directly affects the mechanical strength of articular cartilage, ADC can serve as a potentially useful indicator of the mechanical strength of cartilage. The aim of this study was to investigate the correlation between ADC and viscoelasticity as measured by indentation testing. Fresh porcine knee joints (n = 20, age 6 months) were obtained from a local abattoir. ADC of porcine knee cartilage was measured using a 3-Tesla MRI. Indentation testing was performed on an electromechanical precision-controlled system, and viscosity coefficient and relaxation time were measured as additional indicators of the viscoelasticity of cartilage. The relationship between ADC and viscosity coefficient as well as that between ADC and relaxation time were assessed. ADC was correlated with relaxation time and viscosity coefficient (R(2) = 0.75 and 0.69, respectively, p correlation between ADC and viscoelasticity in the superficial articular cartilage. Both molecular diffusion and viscoelasticity were higher in weight bearing than non-weight-bearing articular cartilage areas.

  11. Current concepts in the rehabilitation following articular cartilage repair procedures in the knee

    National Research Council Canada - National Science Library

    Reinold, Michael M; Wilk, Kevin E; Macrina, Leonard C; Dugas, Jeffrey R; Cain, E Lyle

    2006-01-01

    ... characteristics of the patient, and the type and detail of each surgical procedure. These programs are based on knowledge of the basic science, anatomy, and biomechanics of articular cartilage as well as the biological course of healing following surgery...

  12. Effects of immobilization on thickness of superficial zone of articular cartilage of patella in rats

    Directory of Open Access Journals (Sweden)

    Khadija Iqbal

    2012-01-01

    Conclusion: Each segment of superficial zone behaves differentially on immobilization and remobilization. Perhaps a much longer duration of remobilization is required to reverse changes of immobilization in articular cartilage and plays a significant role in knee joint movements.

  13. Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Magdalena Krajewska-Włodarczyk

    2018-02-01

    Full Text Available Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage.

  14. Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Wen Wang

    2015-05-01

    Full Text Available Mesenchymal stem cells (MSCs are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA. Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

  15. Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player

    Science.gov (United States)

    Silvers, Holly Jacinda; Steinwachs, Matthias

    2012-01-01

    Background: Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial. Objective: The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football player. Design: A review of current literature and the scientific evidence for rehabilitation after articular cartilage repair of the knee. Conclusions: Articular cartilage repair has been shown to allow return to sport but rehabilitation timescales are lengthy. Successful rehabilitation for a return to football after articular cartilage repair of the knee requires the player to be able to accept the load of the sport. This necessitates a multidisciplinary approach to rehabilitation, especially in the transition from therapy to performance care. It should be recognized that not all players will return to football after articular cartilage repair. The evidence base for rehabilitative practice after articular cartilage repair is increasing but remains sparse in areas. PMID:26069608

  16. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    Science.gov (United States)

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may

  17. Delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) can be effectively applied for longitudinal cohort evaluation of articular cartilage regeneration

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Lambertus, W.B.; Benink, R.J.; Tsuchida, A.I.; Vincken, K.L.; Dhert, W.J.A.; Creemers, L.B.; Saris, Daniël B.F.

    2013-01-01

    Objective Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) facilitates non-invasive evaluation of the glycosaminoglycan content in articular cartilage. The primary aim of this study was to show that the dGEMRIC technique is able to monitor cartilage repair following regenerative cartilage

  18. The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

    DEFF Research Database (Denmark)

    Volck, B; Ostergaard, K; Johansen, J S

    1999-01-01

    YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL......-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found...

  19. Clinical potential and challenges of using genetically modified cells for articular cartilage repair

    Science.gov (United States)

    Madry, Henning; Cucchiarini, Magali

    2011-01-01

    Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration. PMID:21674822

  20. Hydrostatic Pressure in Articular Cartilage Tissue Engineering: From Chondrocytes to Tissue Regeneration

    OpenAIRE

    Elder, Benjamin D.; Athanasiou, Kyriacos A.

    2009-01-01

    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) ...

  1. Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.

    Science.gov (United States)

    Li, Lei; Newton, Phillip T; Bouderlique, Thibault; Sejnohova, Marie; Zikmund, Tomas; Kozhemyakina, Elena; Xie, Meng; Krivanek, Jan; Kaiser, Jozef; Qian, Hong; Dyachuk, Vyacheslav; Lassar, Andrew B; Warman, Matthew L; Barenius, Björn; Adameyko, Igor; Chagin, Andrei S

    2017-03-01

    Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by using in vivo genetic approaches. Histone H2B-green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytes via both asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid-enhanced micro-computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self-renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilage de novo, entirely substituting fetal chondrocytes.-Li, L., Newton, P. T., Bouderlique, T., Sejnohova, M., Zikmund, T., Kozhemyakina, E., Xie, M., Krivanek, J., Kaiser, J., Qian, H., Dyachuk, V., Lassar, A. B., Warman, M. L., Barenius, B., Adameyko, I., Chagin, A. S. Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice. © FASEB.

  2. Cell-Based Treatment for the Management of Articular Cartilage Injuries Where Are We?

    Science.gov (United States)

    Rossy, William; Strauss, Eric

    2017-01-01

    Articular cartilage is a specialized tissue that lines the surface of joints. Injuries to articular cartilage pose challenges due to poor healing potential. Focal cartilage defects are typically the result of high impact or repetitive loads to the articular surface. They tend to occur in the younger, active population and have been shown to cause swelling, pain, and joint dysfunction. Although the natural history of these lesions has never been definitively elucidated in the literature, clinical experience suggests that if left untreated, these lesions will demonstrate an inability to heal and may lead to prolonged increased articular peak stresses, which in turn may lead to pain and significant limitations in the future. The purpose of the present review is to provide the most current treatment options for these injuries and review the literature supporting their use.

  3. Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy.

    Science.gov (United States)

    Ellingsen, Pål Gunnar; Lilledahl, Magnus Borstad; Aas, Lars Martin Sandvik; Davies, Catharina de Lange; Kildemo, Morten

    2011-11-01

    The collagen meshwork in articular cartilage of chicken knee is characterized using Mueller matrix imaging and multiphoton microscopy. Direction and degree of dispersion of the collagen fibers in the superficial layer are found using a Fourier transform image-analysis technique of the second-harmonic generated image. Mueller matrix images are used to acquire structural data from the intermediate layer of articular cartilage where the collagen fibers are too small to be resolved by optical microscopy, providing a powerful multimodal measurement technique. Furthermore, we show that Mueller matrix imaging provides more information about the tissue compared to standard polarization microscopy. The combination of these techniques can find use in improved diagnosis of diseases in articular cartilage, improved histopathology, and additional information for accurate biomechanical modeling of cartilage.

  4. Directed differentiation of induced pluripotent stem cells into chondrogenic lineages for articular cartilage treatment

    Directory of Open Access Journals (Sweden)

    Michał Lach

    2014-09-01

    Full Text Available In recent years, increases in the number of articular cartilage injuries caused by environmental factors or pathological conditions have led to a notable rise in the incidence of premature osteoarthritis. Osteoarthritis, considered a disease of civilization, is the leading cause of disability. At present, standard methods for treating damaged articular cartilage, including autologous chondrocyte implantation or microfracture, are short-term solutions with important side effects. Emerging treatments include the use of induced pluripotent stem cells, a technique that could provide a new tool for treatment of joint damage. However, research in this area is still early, and no optimal protocol for transforming induced pluripotent stem cells into chondrocytes has yet been established. Developments in our understanding of cartilage developmental biology, together with the use of modern technologies in the field of tissue engineering, provide an opportunity to create a complete functional model of articular cartilage.

  5. Gene Expression Profiling Reveals Similarities between the Spatial Architectures of Postnatal Articular and Growth Plate Cartilage: e103061

    National Research Council Canada - National Science Library

    Michael Chau; Julian C Lui; Ellie B M Landman; Stephan-Stanislaw Späth; Andrea Vortkamp; Jeffrey Baron; Ola Nilsson

    2014-01-01

      Articular and growth plate cartilage are discrete tissues but arise from a common cartilaginous condensation and have comparable spatial architectures consisting of distinct layers of chondrocytes...

  6. Ultrasonic reflection coefficient and surface roughness index of OA articular cartilage: relation to pathological assessment

    Directory of Open Access Journals (Sweden)

    Niu Hai-jun

    2012-03-01

    Full Text Available Abstract Background Early diagnosis of Osteoarthritis (OA is essential for preventing further cartilage destruction and decreasing severe complications. The aims of this study are to explore the relationship between OA pathological grades and quantitative acoustic parameters and to provide more objective criteria for ultrasonic microscopic evaluation of the OA cartilage. Methods Articular cartilage samples were prepared from rabbit knees and scanned using ultrasound biomicroscopy (UBM. Three quantitative parameters, including the roughness index of the cartilage surface (URI, the reflection coefficients from the cartilage surface (R and from the cartilage-bone interface (Rbone were extracted. The osteoarthritis grades of these cartilage samples were qualitatively assessed by histology according to the grading standards of International Osteoarthritis Institute (OARSI. The relationship between these quantitative parameters and the osteoarthritis grades was explored. Results The results showed that URI increased with the OA grade. URI of the normal cartilage samples was significantly lower than the one of the OA cartilage samples. There was no significant difference in URI between the grade 1 cartilage samples and the grade 2 cartilage samples. The reflection coefficient of the cartilage surface reduced significantly with the development of OA (p Conclusion High frequency ultrasound measurements can reflect the changes in the surface roughness index and the ultrasound reflection coefficients of the cartilage samples with different OA grades. This study may provide useful information for the quantitative ultrasonic diagnosis of early OA.

  7. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration.

    Science.gov (United States)

    Elder, Benjamin D; Athanasiou, Kyriacos A

    2009-03-01

    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction.

  8. Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 Months in a Goat Model

    Science.gov (United States)

    Chan, Elaine F.; Liu, I-Ling; Semler, Eric J.; Aberman, Harold M.; Simon, Timothy M.; Chen, Albert C.; Truncale, Kate G.

    2012-01-01

    Objective: The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-dimensional (3-D) geometrical match between grafted and contralateral joints at 6 and 12 months after surgery. Design: Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral nonoperated joints were harvested at 6 and 12 months and analyzed by indentation testing, micro–computed tomography, and histology to compare 1) histological indices of repair, 2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), 3) indentation stiffness, and 4) correlations between stiffness and 3-D structure. Results: Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of the operated MFC were lower than the nonoperated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to the nonoperated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness. Conclusion: The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure. PMID:24224069

  9. The bio in the ink : cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

    NARCIS (Netherlands)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie|info:eu-repo/dai/nl/304817856; van Weeren, P. René; Khan, Ilyas M.; Malda, Jos

    2017-01-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of

  10. The study on the mechanical characteristics of articular cartilage in simulated microgravity

    Science.gov (United States)

    Niu, Hai-Jun; Wang, Qing; Wang, Yue-Xiang; Li, Ang; Sun, Lian-Wen; Yan, Yan; Fan, Fan; Li, De-Yu; Fan, Yu-Bo

    2012-10-01

    The microgravity environment of a long-term space flight may induce acute changes in an astronaut's musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from (6.31 ± 3.37)MPa to (5.05 ± 2.98)MPa ( p < 0.05). The histology-stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.

  11. Influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage.

    Science.gov (United States)

    Brama, P A; TeKoppele, J M; Bank, R A; van Weeren, P R; Barneveld, A

    1999-03-01

    To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. Articular cartilage specimens from 53 horses 4 to 30 years old. Healthy specimens were obtained from 2 locations on the proximal articular surface of the first phalanx that had different disease prevalences (site 1 at the mediodorsal margin and site 2 at the center of the medial cavity). Water, total collagen, and hydroxylysine contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic (pentosidine) crosslinking were determined at both sites. Differences between sites were analyzed by ANOVA (factors, site, and age), and age correlation was tested by Pearson's product-moment correlation analysis. Significance was set at Pcollagen, hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking was higher in older horses and was linearly related to age (r = 0.94). Water and collagen contents and HP and pentosidine crosslinks were significantly higher at site 1. Hydroxylysine content was significantly lower at site 1. Except for nonenzymatic glycation, the composition of articular cartilage collagen does not change significantly in adult horses. A significant topographic variation exists in biochemical characteristics of the articular cartilage collagen network in equine metacarpophalangeal joints. These differences may influence local biomechanical properties and, hence, susceptibility to osteochondral disease, as will greater pentosidine crosslinks in older horses that are likely to cause stiffer and more brittle cartilage.

  12. Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation

    Science.gov (United States)

    Torqabeh, Alireza Abazari

    Loading vitrifiable concentrations of cryoprotective agents is an important step for cryopreservation of biological tissues by vitrification for research and transplantation purposes. This may be done by immersing the tissue in a cryoprotective agent (CPA) solution, and increasing the concentration, continuously or in multiple steps, and simultaneously decreasing the temperature to decrease the toxicity effects of the cryoprotective agent on the tissue cellular system. During cryoprotective agent loading, osmotic water movement from the tissue to the surrounding solution, and the resultant tissue shrinkage and stress-strain in the tissue matrix as well as on the cellular system can significantly alter the outcome of the cryopreservation protocol. In this thesis, a biomechanical model for articular cartilage is developed to account for the transport of the cryoprotective agent, the nonideal-nondilute properties of the vitrifiable solutions, the osmotic water movement and the resultant tissue shrinkage and stress-strain in the tissue matrix, and the osmotic volume change of the chondrocytes, during cryoprotective agent loading in the cartilage matrix. Four essential transport parameters needed for the model were specified, the values of which were obtained uniquely by fitting the model to experimental data from porcine articular cartilage. Then, it was shown that using real nonuniform initial distributions of water and fixed charges in cartilage, measured separately in this thesis using MRI, in the model can significantly affect the model predictions. The model predictions for dimethyl sulfoxide diffusion in porcine articular cartilage were verified by comparing to spatially and temporally resolved measurements of dimethyl sulfoxide concentration in porcine articular cartilage using a spectral MRI technique, developed for this purpose and novel to the field of cryobiology. It was demonstrated in this thesis that the developed mathematical model provides a novel tool

  13. Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage.

    Directory of Open Access Journals (Sweden)

    Catherine A Bautista

    Full Text Available Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 μm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods.

  14. Irrigating solutions used in arthroscopy and their effect on articular cartilage. An in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Arciero, R.A.; Little, J.S.; Liebenberg, S.P.; Parr, T.J.

    1986-11-01

    The effect of arthroscopic irrigating solutions on articular cartilage was determined by the use of an animal model. Rabbit knee joints were irrigated continuously for two hours with either normal saline, Ringer's lactate, or sterile water. Subsequently, the rate of incorporation of /sup 35/SO/sub 4/ by articular cartilage was used to measure the effect of the irrigants on chondrocyte metabolism. In addition, the irrigated groups were compared to an unirrigated control group. There was no significant difference in /sup 35/SO/sub 4/ incorporation between the groups. This suggested that none of the irrigating solutions used in this study adversely affected articular cartilage function. On the basis of these findings, it appears that normal saline, Ringer's lactate, and sterile water can be safely used as irrigating solutions during most arthroscopic procedures.

  15. Type I collagen-based fibrous capsule enhances integration of tissue-engineered cartilage with native articular cartilage.

    Science.gov (United States)

    Yang, Yueh-Hsun; Ard, Mary B; Halper, Jaroslava T; Barabino, Gilda A

    2014-04-01

    Successful integration of engineered constructs with host tissues is crucial for cartilage repair, yet achieving it remains challenging. A collagen I-based fibrous capsule characterized by increased cell density and decreased glycosaminoglycan deposition usually forms at the periphery of tissue-engineered cartilage. The current study aimed to evaluate the effects of a solid fibrous capsule on construct integration with native articular cartilage. To this end, capsule-containing (CC) and capsule-free (CF) constructs were grown by culturing chondrocyte-seeded scaffolds with insulin-like growth factor-1 and transforming growth factor-β1, respectively, in a wavy-walled bioreactor that imparts hydrodynamic forces for 4 weeks. The ability of harvested constructs to integrate with native cartilage was determined using a cartilage explant model. Our results revealed that adhesive stress between native cartilage and the CC constructs was 57% higher than that in the CF group, potentially due to the absence of glycosaminoglycans and increased cell density in the capsule region and deposition of denser and thicker collagen fibrils at the integration site. The present work demonstrates that the fibrous capsule can effectively enhance early integration of engineered and native cartilage tissues and thus suggests the need to include the capsule as a variable in the development of cartilage tissue engineering strategies.

  16. Development of methods for analysis of knee articular cartilage degeneration by magnetic resonance imaging data

    Science.gov (United States)

    Suponenkovs, Artjoms; Glazs, Aleksandrs; Platkajis, Ardis

    2017-03-01

    The aim of this paper is to describe the new methods for analyzing knee articular cartilage degeneration. The most important aspects regarding research about magnetic resonance imaging, knee joint anatomy, stages of knee osteoarthritis, medical image segmentation and relaxation times calculation. This paper proposes new methods for relaxation times calculation and medical image segmentation. The experimental part describes the most important aspect regarding analysing of articular cartilage relaxation times changing. This part contains experimental results, which show the codependence between relaxation times and organic structure. These experimental results and proposed methods can be helpful for early osteoarthritis diagnostics.

  17. [Basophilic line of the articular cartilage in normal and various pathological states].

    Science.gov (United States)

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance.

  18. Cdc42 is essential for both articular cartilage degeneration and subchondral bone deterioration in experimental osteoarthritis.

    Science.gov (United States)

    Hu, Xinhua; Ji, Xing; Yang, Mengting; Fan, Shihao; Wang, Jirong; Lu, Meiping; Shi, Wei; Mei, Liu; Xu, Chengyun; Fan, Xueying; Hussain, Musaddique; Du, Jingyu; Wu, Junsong; Wu, Ximei

    2018-01-03

    Cdc42, a member of Rho family small GTPases, is critical for cartilage development. We investigated the roles of Cdc42 in osteoarthritis and explored the potential mechanism underlying Cdc42-mediated articular cartilage degeneration and subchondral bone deterioration. Cdc42 is highly expressed in both articular cartilage and subchondral bone in a mouse osteoarthritis model with surgical destabilisation of the medial meniscus (DMM) in the knee joints. Specifically, genetic disruption of Cdc42, knockdown of Cdc42 expression, or inhibition of Cdc42 activity robustly attenuates the DMM-induced destruction, hypertrophy, high expression of matrix metallopeptidase-13 and collagen X, and activation of Stat3 in articular cartilages. Notably, genetic disruption of Cdc42, knockdown of Cdc42 expression or inhibition of Cdc42 activity significantly restored the increased numbers of mesenchymal stem cells, osteoprogenitors, osteoblasts, osteoclasts, and neovascularised vessels, the increased bone mass, and the activated Erk1/2, Smad1/5 and Smad2 in subchondral bone of DMM-operated mice. Mechanistically, Cdc42 mediates interleukin-1β-induced interleukin-6 production and subsequent Jak/Stat3 activation to regulate chondrocytic inflammation, and also lies upstream of Erk/Smads to regulate subchondral bone remodelling during transform growth factor-β1 signalling. Cdc42 is apparently required for both articular cartilage degeneration and subchondral bone deterioration of osteoarthritis, thus, interventions targeting Cdc42 have potential in osteoarthritic therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Development of an Electromechanical Grade to Assess Human Knee Articular Cartilage Quality.

    Science.gov (United States)

    Sim, Sotcheadt; Hadjab, Insaf; Garon, Martin; Quenneville, Eric; Lavigne, Patrick; Buschmann, Michael D

    2017-10-01

    Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.

  20. Effects of sodium hyaluronate and methylprednisolone acetate on proteoglycan synthesis in equine articular cartilage explants.

    Science.gov (United States)

    Doyle, Aimie J; Stewart, Allison A; Constable, Peter D; Eurell, Jo Ann C; Freeman, David E; Griffon, Dominique J

    2005-01-01

    To determine effects of sodium hyaluronate (HA) on corticosteroid-induced cartilage matrix catabolism in equine articular cartilage explants. 30 articular cartilage explants from fetlock joints of 5 adult horses without joint disease. Articular cartilage explants were treated with control medium or medium containing methylprednisolone acetate (MPA; 0.05, 0.5, or 5.0 mg/mL), HA (0.1, 1.0, or 1.5 mg/mL), or both. Proteoglycan (PG) synthesis was measured by incorporation of sulfur 35-labeled sodium sulphate into PGs, and PG degradation was measured by release of radiolabeled PGs into the medium. Total glycosaminoglycan (GAG) content in media and explants and total explant DNA were determined. Methylprednisolone acetate caused a decrease in PG synthesis, whereas HA had no effect. Only the combination of MPA at a concentration of 0.05 mg/mL and HA at a concentration of 1.0 mg/mL increased PG synthesis, compared with control explants. Methylprednisolone acetate increased degradation of newly synthesized PGs into the medium, compared with control explants, and HA alone had no effect. Hyaluronate had no effect on MPA-induced PG degradation and release into media. Neither MPA alone nor HA alone had an effect on total cartilage GAG content. Methylprednisolone acetate caused an increase in release of GAG into the medium at 48 and 72 hours after treatment. In combination, HA had no protective effect on MPA-induced GAG release into the medium. Total cartilage DNA content was not affected by treatments. Our results indicate that HA addition has little effect on corticosteroid-induced cartilage matrix PG catabolism in articular cartilage explants.

  1. Cartilage lesions in feline stifle joints - Associations with articular mineralizations and implications for osteoarthritis.

    Science.gov (United States)

    Leijon, Alexandra; Ley, Charles J; Corin, Antonia; Ley, Cecilia

    2017-10-01

    Feline stifle osteoarthritis (OA) is common, however little is known about the early stages of the disease. Furthermore, the importance of small articular mineralizations (AMs) in feline stifle OA is controversial. This study aimed to describe microscopic articular cartilage lesions and to investigate associations between cartilage lesions and AMs, synovitis, osteochondral junction findings and subchondral bone sclerosis. Stifles of 29 cats, aged 1-23years and euthanized for reasons other than stifle disease, were examined. Osteochondral tissue and synovial membrane changes were histologically evaluated. Computed tomography and radiography were used for evaluation of AMs. Global cartilage scores (GCS, n=28) were summarized and joints assigned a histologic OA grade. Minimal to mild histologic OA was seen in 24/28 joints. In 27/29 joints tibial cartilage lesions were seen, whereas femoral lesions were only seen in two joints. Articular mineralizations were detected in 13/29 joints, 11 were small and 12 were located entirely within the medial meniscus. There was no association between GCS and presence or volumes of AMs. However, higher GCS was associated with synovitis (P=0.001) and age (P<0.0005). Presence of subchondral bone sclerosis (P<0.0005) and disruption of the calcified cartilage or tidemark (P<0.0005) were associated with cartilage lesions. We conclude that the tibial articular cartilage is a common location for histologic OA lesions in cats. Synovitis and changes in the subchondral bone and calcified cartilage may be important in the pathogenesis of feline stifle OA, whereas small AMs likely represent incidental findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Articular calcified cartilage canals in the third metacarpal bone of 2-year-old thoroughbred racehorses

    Science.gov (United States)

    Boyde, A; Firth, E C

    2004-01-01

    We describe morphological aspects of the articular calcified cartilage mineralizing front ‘tidemark’ in the distal joint surface of the third metacarpal bone from 14 horses. Compositional backscattered electron scanning electron microscopy and confocal scanning light microscopy were conducted on polymethylmethacrylate (PMMA)-embedded medio-lateral slices. After maceration, scanning electron microscopy (SEM) was used to study the calcified cartilage surface in the ‘wedges’ intervening between the slices. An anatomically reproducible clustering of canals in the calcified cartilage was found at one site on the sagittal ridge in all the horses. The site is one that is relatively less loaded during joint function. These canals through calcified cartilage result from osteoclastic resorption (cutting cones) penetrating from bone through to the non-mineralized hyaline articular cartilage. Their presence may indicate a pathway for connection between bone and cartilage extracellular fluid. In one horse, repair of such canals by plugging with new calcified cartilage was demonstrated. Differences in the degree of mineralization of regions of cartilage were seen in the combined compositional-cum-topographical backscattered SEM images of the macerated ‘tidemark’ front. More-or-less circular patches of lower mineralization density were frequently centred on (and may possibly originate from) canals. These microanatomical features should be searched for in other joints, at other ages and in other species to discover their frequency and significance. PMID:15610396

  3. BMP receptor signaling is required for postnatal maintenance of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Ryan B Rountree

    2004-11-01

    Full Text Available Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be

  4. Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee.

    Science.gov (United States)

    Lee, C R; Grodzinsky, A J; Hsu, H P; Martin, S D; Spector, M

    2000-09-01

    This study utilizes a canine model to quantify changes in articular cartilage 15-18 weeks after a knee joint is subjected to surgical treatment of isolated chondral defects. Clinical and experimental treatment of articular cartilage defects may include implantation of matrix materials or cells, or both. Three cartilage repair methods were evaluated: microfracture, microfracture and implantation of a type-II collagen matrix, and implantation of an autologous chondrocyte-seeded collagen matrix. The properties of articular cartilage in other knee joints subjected to harvest of articular cartilage from the trochlear ridge (to obtain cells for the cell-seeded procedure) were also evaluated. Physical properties (thickness, equilibrium compressive modulus, dynamic compressive stiffness, and streaming potential) and biochemical composition (hydration, glycosaminoglycan content, and DNA content) of the cartilage from sites distant to the surgical treatment were compared with values measured for site-matched controls in untreated knee joints. No significant differences were seen in joints subjected to any of the three cartilage repair procedures. However, a number of changes were induced by the harvest operation. The largest changes (displaying up to 3-fold increases) were seen in dynamic stiffness and streaming potential of patellar groove cartilage from joints subjected to the harvest procedure. Whether the changes reported will lead to osteoarthritic degeneration is unknown, but this study provides evidence that the harvest procedure associated with autologous cell transplantation for treatment of chondral defects may result in changes in the articular cartilage in the joint.

  5. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage.

    Science.gov (United States)

    Wakitani, S; Goto, T; Pineda, S J; Young, R G; Mansour, J M; Caplan, A I; Goldberg, V M

    1994-04-01

    Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits. Adherent cells from bone marrow, or cells from the periosteum that had been liberated from connective tissue by collagenase digestion, were grown in culture, dispersed in a type-I collagen gel, and transplanted into a large (three-by-six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either the defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed similar patterns of differentiation into articular cartilage and subchondral bone. Specimens of reparative tissue were analyzed with use of a semiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cells from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor cells had uniformly differentiated into chondrocytes throughout the defects. This repair cartilage was subsequently replaced with bone in a proximal-to-distal direction, until, at twenty-four weeks after transplantation, the subchondral bone was completely repaired, without loss of overlying articular cartilage. The mechanical testing data were a useful index of the quality of the long-term repair. Twenty-four weeks after transplantation, the reparative tissue of both the bone-marrow and the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage. The current modalities for the repair of defects of the articular cartilage have many

  6. Biologic Options for Articular Cartilage Wear (Platelet-Rich Plasma, Stem Cells, Bone Marrow Aspirate Concentrate).

    Science.gov (United States)

    Kraeutler, Matthew J; Chahla, Jorge; LaPrade, Robert F; Pascual-Garrido, Cecilia

    2017-07-01

    Biological treatments for articular cartilage repair have gained in popularity in the past decade. Advantages of these therapies include minimal invasiveness, improved healing time, and faster recovery. Biological therapies for cartilage repair include platelet-rich plasma, bone marrow aspirate concentrate, and cell-based therapies. These methods have the added benefit of containing growth factors and/or stem cells that aid in recovery and regeneration. The purpose of this article is to review the current cartilage treatment options and the existing literature on outcomes, complications, and safety profile of these products for use in the knee and hip joints. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Ageing is associated with reduction of mechanically-induced activation of Smad2/3P signaling in articular cartilage

    NARCIS (Netherlands)

    Madej, W.M.; Caam, A.P.M. van; Blaney Davidson, E.N.; Hannink, G.J.; Buma, P.; Kraan, P.M. van der

    2016-01-01

    OBJECTIVE: Mechanical signals control key cellular processes in articular cartilage. Previously we have shown that mechanical compression is an important ALK5/Smad2/3P activator in cartilage explants. However, age-related changes in the cartilage are known to affect tissue mechanosensitivity and

  8. Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers.

    Science.gov (United States)

    Boeuf, S; Steck, E; Pelttari, K; Hennig, T; Buneb, A; Benz, K; Witte, D; Sültmann, H; Poustka, A; Richter, W

    2008-01-01

    Mesenchymal stem cells (MSCs) are a population of cells broadly discussed to support cartilage repair. The differentiation of MSCs into articular chondrocytes is, however, still poorly understood on the molecular level. The aim of this study was to perform an almost genome-wide screen for genes differentially expressed between cartilage and MSCs and to extract new markers useful to define chondrocyte differentiation stages. Gene expression profiles of MSCs (n=8) and articular cartilage from OA patients (n=7) were compared on a 30,000 cDNA-fragment array and differentially expressed genes were extracted by subtraction. Expression of selected genes was assessed during in vitro chondrogenic differentiation of MSCs and during dedifferentiation of expanded chondrocytes using quantitative and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Protein secretion was measured by enzyme-linked immunosorbent assay. Eighty-seven genes were differentially expressed between MSCs and cartilage with a more than three-fold difference. Sixty-seven of them were higher expressed in cartilage and among them 15 genes were previously not detected in cartilage. Differential expression was confirmed for 69% of 26 reanalysed genes by RT-PCR. The profiles of three unknown transcripts and six protease-related molecules were characterised during differentiation. SERPINA1 and SERPINA3 mRNA expression correlated with chondrogenic differentiation of MSCs and dedifferentiation of chondrocytes, and SERPINA1 protein levels in culture supernatants could be correlated alike. cDNA-array analysis identified SERPINA1 and A3 as new differentiation-relevant genes for cartilage. Since SERPINA1 secretion correlated with both chondrogenesis of MSCs and dedifferentiation during chondrocyte expansion, it represents an attractive marker for refinement of chondrocyte differentiation.

  9. Presence and mechanism of knee articular cartilage degeneration after meniscal reconstruction in dogs

    NARCIS (Netherlands)

    van Tienen, TG; Heijkants, RGJC; de Groot, JH; Pennings, AJ; Poole, AR; Veth, RPH; Buma, P

    Objective: Partial meniscectomy is the golden standard for treating a bucket-handle tear in the meniscus of the knee, but it inevitably leads to articular cartilage degeneration. Surgical creation of an access channel between the lesion and the vascularized synovial lining is intended to induce

  10. Presence and mechanism of knee articular cartilage degeneration after meniscal reconstruction in dogs.

    NARCIS (Netherlands)

    Tienen, Tony van; Heijkants, R.G.J.C.; Groot, J.H. de; Pennings, A.J.; Poole, A.R.; Veth, R.P.H.; Buma, P.

    2003-01-01

    OBJECTIVE: Partial meniscectomy is the golden standard for treating a bucket-handle tear in the meniscus of the knee, but it inevitably leads to articular cartilage degeneration. Surgical creation of an access channel between the lesion and the vascularized synovial lining is intended to induce

  11. Glucosamine:chondroitin or ginger root extract have little effect on articular cartilage in swine

    Science.gov (United States)

    Sows are culled at a high rate from breeding herds due to musclo-skeletal problems and lameness. Research in our laboratory has shown that even first-parity sows have significant amounts of osteochondritic lesions of their articular cartilage. Glusoamine chondroitin and ginger root extract have both...

  12. Topographical mapping of biochemical properties of articular cartilage in the equine fetlock joint

    NARCIS (Netherlands)

    Brama, P.A.J.; Tekoppele, J.M.; Bank, R.A.; Karssenberg, D.; Barneveld, A.; Weeren, P.R. van

    2000-01-01

    The aim of this study was to evaluate topographical differences in the biochemical composition of the extracellular matrix of articular cartilage of the normal equine fetlock joint. Water content, DNA content, glycosaminoglycan (GAG) content and a number of characteristics of the collagen network

  13. THE EFFECT IN-VITRO OF IRRIGATING SOLUTIONS ON INTACT RAT ARTICULAR-CARTILAGE

    NARCIS (Netherlands)

    Bulstra, Sjoerd K; KUIJER, R; EERDMANS, P; VANDERLINDEN, AJ

    Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake

  14. Age-related accumulation of Maillard reaction products in human articular cartilage collagen

    NARCIS (Netherlands)

    Verzijl, N.; Degroot, J.; Oldehinkel, E.; Bank, R. A.; Thorpe, S. R.; Baynes, J. W.; Bayliss, M. T.; Bijlsma, J. W.; Lafeber, F. P.; TeKoppele, J. M.

    2000-01-01

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated

  15. Interaction of chondrocytes, extracellular matrix and growth factors: relevance for articular cartilage tissue engineering.

    NARCIS (Netherlands)

    Kraan, P.M. van der; Buma, P.; Kuppevelt, A.H.M.S.M. van; Berg, W.B. van den

    2002-01-01

    The abundant extracellular matrix of articular cartilage has to be maintained by a limited number of chondrocytes. Vice versa, the extracellular matrix has an important role in the regulation of chondrocyte function. OBJECTIVE: In this review we discuss the role of the extracellular matrix in the

  16. Development of biochemical heterogeneity of articular cartilage: Influences of age and exercise

    NARCIS (Netherlands)

    Brama, P.A.J.; Tekoppele, J.M.; Bank, R.A.; Barneveld, A.; Weeren, P.R. van

    2002-01-01

    The objective of this study was to document the development of biochemical heterogeneity from birth to maturity in equine articular cartilage, and to test the hypothesis that the amount of exercise during early life may influence this process. Neonatal foals showed no biochemical heterogeneity

  17. In vitro effects of methotrexate on human articular cartilage and bone-derived osteoblasts

    NARCIS (Netherlands)

    van der Veen, M. J.; Scheven, B. A.; van Roy, J. L.; Damen, C. A.; Lafeber, F. P.; Bijlsma, J. W.

    1996-01-01

    Conflicting data have been published on whether low-dose methotrexate (MTX) treatment of rheumatoid arthritis (RA) is able to slow down radiological joint damage, i.e. retard the destruction of articular cartilage and (subchondral) bone. We studied the effects of MTX on proteoglycan (PG) turnover

  18. Effects of initial cell seeding in self assembly of articular cartilage.

    Science.gov (United States)

    Revell, Christopher M; Reynolds, Catherine E; Athanasiou, Kyriacos A

    2008-09-01

    Current forays into tissue engineering of articular cartilage in vitro using the self-assembling method have produced constructs possessing significant extracellular matrix and resulting mechanical properties. However, large numbers of native articular chondrocytes are necessary to produce functional engineered cartilage; all previous work with the self-assembling process has used 5.5 x 10(6) cells/construct. In this study, the effects of initial cell seeding (0.25-11 x 10(6) cells/construct) on tissue quality were investigated. Results showed that tissue engineered articular cartilage was formed, when using at least 2 million cells/construct, possessing dimensional, compositional, and compressive properties approaching those of native tissue. It was noted that higher seeding contributed to thicker constructs with larger diameters and had a significant effect on resulting biochemical and biomechanical properties. It was further observed that aggregate modulus increased with increased seeding. By combining gross morphological, histological, biochemical, and biomechanical results, an optimal initial seeding for the self-assembling process of 3.75 x 10(6) cells/construct was identified. This finding enhances the translatability of this tissue engineering process by reducing the number of cells needed for tissue engineering of articular cartilage by 32% while maintaining essential tissue properties.

  19. Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament.

    Science.gov (United States)

    Sah, R L; Yang, A S; Chen, A C; Hant, J J; Halili, R B; Yoshioka, M; Amiel, D; Coutts, R D

    1997-03-01

    The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.

  20. Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses.

    Science.gov (United States)

    te Moller, N C R; Brommer, H; Liukkonen, J; Virén, T; Timonen, M; Puhakka, P H; Jurvelin, J S; van Weeren, P R; Töyräs, J

    2013-09-01

    Arthroscopy enables direct inspection of the articular surface, but provides no information on deeper cartilage layers. Optical coherence tomography (OCT), based on measurement of reflection and backscattering of light, is a diagnostic technique used in cardiovascular surgery and ophthalmology. It provides cross-sectional images at resolutions comparable to that of low-power microscopy. The aim of this study was to determine if OCT is feasible for advanced clinical assessment of lesions in equine articular cartilage during diagnostic arthroscopy. Diagnostic arthroscopy of 36 metacarpophalangeal joints was carried out ex vivo. Of these, 18 joints with varying degrees of cartilage damage were selected, wherein OCT arthroscopy was conducted using an OCT catheter (diameter 0.9 mm) inserted through standard instrument portals. Five sites of interest, occasionally supplemented with other locations where defects were encountered, were arthroscopically graded according to the International Cartilage Repair Society (ICRS) classification system. The same sites were evaluated qualitatively (ICRS classification and morphological description of the lesions) and quantitatively (measurement of cartilage thickness) on OCT images. OCT provided high resolution images of cartilage enabling determination of cartilage thickness. Comparing ICRS grades determined by both arthroscopy and OCT revealed poor agreement. Furthermore, OCT visualised a spectrum of lesions, including cavitation, fibrillation, superficial and deep clefts, erosion, ulceration and fragmentation. In addition, with OCT the arthroscopically inaccessible area between the dorsal MC3 and P1 was reachable in some cases. Arthroscopically-guided OCT provided more detailed and quantitative information on the morphology of articular cartilage lesions than conventional arthroscopy. OCT could therefore improve the diagnostic value of arthroscopy in equine orthopaedic surgery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism.

    Science.gov (United States)

    Beluche, L A; Bertone, A L; Anderson, D E; Rohde, C

    2001-12-01

    To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1beta in articular cartilage explants of horses. 11 healthy 1- to 2-year-old horses. Horses were randomly assigned to the control (n = 5) or treated group (4.4 mg of phenylbutazone/kg of body weight, p.o., q 12 h; n = 6). Articular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment (day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with recombinant human interleukin-1beta (IL-1beta; 0.1 ng/ml). On day 0, proteoglycan synthesis was significantly less in cartilage explants cultured in IL-1beta, compared with medium alone. Mean proteoglycan synthesis in explants collected on days 14 and 30 was significantly less in treated horses, compared with controls. However, incubation of explants from treated horses with IL-1beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentration were not detected between or within groups. Oral administration of phenylbutazone for 14 days significantly decreased proteoglycan synthesis in articular culture explants from healthy horses to a degree similar to that induced by in vitro exposure to IL-1beta. Phenylbutazone should be used judiciously in athletic horses with osteoarthritis, because chronic administration may suppress proteoglycan synthesis and potentiate cartilage damage.

  2. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics

    OpenAIRE

    ?uczkiewicz, Piotr; Daszkiewicz, Karol; Chr??cielewski, Jacek; Wojciech WITKOWSKI; Winklewski, Pawel J

    2016-01-01

    Objective Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. Methods The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent ...

  3. Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage.

    Science.gov (United States)

    McCulloch, Ryan S; Ashwell, Melissa S; O'Nan, Audrey T; Mente, Peter L

    2012-11-12

    Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein-zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species.

  4. Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage

    Directory of Open Access Journals (Sweden)

    McCulloch Ryan S

    2012-11-01

    Full Text Available Abstract Background Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Results Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A, ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein—zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. Conclusions BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species.

  5. Meniscus, articular cartilage and nucleus pulposus: a comparative review of cartilage-like tissues in anatomy, development and function.

    Science.gov (United States)

    Chen, Song; Fu, Peiliang; Wu, Haishan; Pei, Ming

    2017-10-01

    The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral disc damage, knee replacement surgeries, etc.) is daunting in light of substantial economic and social stresses. This review strives to broaden the scope of regenerative medicine and tissue engineering approaches used for cartilage repair by comparing and contrasting the anatomical and functional nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many review papers have provided detailed evaluations of these cartilages and cartilage-like tissues individually but none have comprehensively examined the parallels and inconsistencies in signaling, genetic expression and extracellular matrix composition between tissues. For the first time, this review outlines the importance of understanding these three tissues as unique entities, providing a comparative analysis of anatomy, ultrastructure, biochemistry and function for each tissue. This novel approach highlights the similarities and differences between tissues, progressing research toward an understanding of what defines each tissue as distinctive. The goal of this paper is to provide researchers with the fundamental knowledge to correctly engineer the meniscus, AC and NP without inadvertently developing the wrong tissue function or biochemistry.

  6. Experimentally Induced Articular Cartilage Injury: The Combined Use of Misoprostol and Diclofenac as Therapeutic Agents.

    Science.gov (United States)

    Plaza, Veronica L.; Thonar, Eugene J-M. A.; Williams, James M.

    1996-03-01

    Injection of chymopapain (CP) into the rabbit knee causes rapid depletion of proteoglycans (PGs) in the articular cartilage. Successful repair of the articular cartilage follows injection of only 0.2 mg CP whereas in animals injected with 0.2 mg CP, the repair phase fails leading to cartilage destruction within 21 days. Previous work by the authors indicated that daily oral diclofenac reduced the severity and incidence of CP-induced cartilage injury after 21 days. The present study was designed to determine if administration of diclofenac promoted articular cartilage repair after CP injury over a longer period of time and if coadministration with misoprostol could reduce the concentration of diclofenac needed to promote repair as well as confer protection to the gastric mucosa. Adolescent male New Zealand white rabbits received CP-induced cartilage injury (2.0 mg) followed by daily oral diclofenac, diclofenac/misoprostol or misoprostol. Control animals received diclofenac, diclofenac/misoprostol, or misoprostol or no drug treatment with no cartilage injury. All animals were sacrificed after 2 months. Examination of the stomachs from animals receiving no drug or misoprostol only were completely normal. Most animals receiving diclofenac only had abnormal gastric mucosa. In contrast, coadministration of diclofenac/misoprostol revealed significantly fewer abnormalities. Analysis of the composite histologic score of patellae and measurements of cartilage PG content revealed no significant differences in groups which received CP injury with and without drug treatment. Histology scores and cartilage PG content from animals in groups which did not receive CP injury, but were treated with diclofenac/misoprostol, diclofenac or misoprostol were within normal limits and thus did not differ significantly from untreated control cartilage. The results of this study indicate that daily administration of diclofenac, diclofenac/misoprostol or misoprostol has no protective effect on

  7. SOX trio decrease in the articular cartilage with the advancement of osteoarthritis.

    Science.gov (United States)

    Lee, Jai-Sun; Im, Gun-Il

    2011-01-01

    SOX trio (SOX-5, SOX-6, and SOX-9) maintain the chondrocytic phenotypes and are vital for chondrogenesis in embryonic development. The purpose of this study is to investigate the change in the expression of SOX trio with the advancement of osteoarthritis (OA) in human articular cartilage (AC). Human OA samples from eight patients were obtained from the distal femoral condyles during total knee arthroplasty. Minimally OA cartilage taken from areas with no obvious surface defects on lateral condyles was compared with advanced OA cartilage obtained from areas within 1 cm of overt lesion located on medial condyle surface. SOX-5, SOX-6, and SOX-9 gene expressions significantly decreased by 41% (p = 0.047), 46% (p = 0.047), and 56% (p = 0.029) in advanced OA area compared with the minimally OA area. There was a significant decrease in aggrecan and type II collagen (COL2A1) gene expressions by 73% (p = 0.029) and 65% (p = 0.029), respectively, in advanced OA area compared with the minimally OA area. From Western blotting and immunohistochemistry, SOX-5, SOX-6, SOX-9, type II collagen, and aggrecan protein expressions also significantly decreased in advanced OA cartilage compared with minimally OA cartilage. DNA methylation study of SOX-9 promoter regions revealed no difference in the epigenetic status between the two areas. It is concluded that SOX trio gene and protein decreased with advancement of OA in human articular cartilage.

  8. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair

    Science.gov (United States)

    Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project

  9. Application of multiphysics models to efficient design of experiments of solute transport across articular cartilage.

    Science.gov (United States)

    Pouran, Behdad; Arbabi, Vahid; Weinans, Harrie; Zadpoor, Amir A

    2016-11-01

    Transport of solutes helps to regulate normal physiology and proper function of cartilage in diarthrodial joints. Multiple studies have shown the effects of characteristic parameters such as concentration of proteoglycans and collagens and the orientation of collagen fibrils on the diffusion process. However, not much quantitative information and accurate models are available to help understand how the characteristics of the fluid surrounding articular cartilage influence the diffusion process. In this study, we used a combination of micro-computed tomography experiments and biphasic-solute finite element models to study the effects of three parameters of the overlying bath on the diffusion of neutral solutes across cartilage zones. Those parameters include bath size, degree of stirring of the bath, and the size and concentration of the stagnant layer that forms at the interface of cartilage and bath. Parametric studies determined the minimum of the finite bath size for which the diffusion behavior reduces to that of an infinite bath. Stirring of the bath proved to remarkably influence neutral solute transport across cartilage zones. The well-stirred condition was achieved only when the ratio of the diffusivity of bath to that of cartilage was greater than ≈1000. While the thickness of the stagnant layer at the cartilage-bath interface did not significantly influence the diffusion behavior, increase in its concentration substantially elevated solute concentration in cartilage. Sufficient stirring attenuated the effects of the stagnant layer. Our findings could be used for efficient design of experimental protocols aimed at understanding the transport of molecules across articular cartilage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Topographical mapping of biochemical properties of articular cartilage in the equine fetlock joint.

    Science.gov (United States)

    Brama, P A; Tekoppele, J M; Bank, R A; Karssenberg, D; Barneveld, A; van Weeren, P R

    2000-01-01

    The aim of this study was to evaluate topographical differences in the biochemical composition of the extracellular matrix of articular cartilage of the normal equine fetlock joint. Water content, DNA content, glycosaminoglycan (GAG) content and a number of characteristics of the collagen network (total collagen content, levels of hydroxylysine- (Hyl) and the crosslink hydroxylysylpyridinoline, (HP) of articular cartilage in the proximal 1st phalanx (P1), distal 3rd metacarpal bone (MC), and proximal sesamoid bones (PSB) were determined in the left and right fetlock joint of 6 mature horses (age 5-9 years). Twenty-eight sites were sampled per joint, which included the clinically important areas often associated with pathology. Biochemical differences were evaluated between sampling sites and related with the predisposition for osteochondral injury and type of loading. Significant regional differences in the composition of the extracellular matrix existed within the joint. Furthermore, left and right joints exhibited biochemical differences. Typical topographic distribution patterns were observed for each parameter. In P1 the dorsal and palmar articular margin showed a significantly lower GAG content than the more centrally located sites. Collagen content and HP crosslinks were higher at the joint margins than in the central area. Also, in the MC, GAG content was significantly lower at the (dorsal) articular margin compared with the central area. Consistent with findings in P1, collagen and HP crosslinks were significantly lower in the central area compared to the (dorsal) articular margin. Biochemical and biomechanical heterogeneity of articular cartilage is supposed to reflect the different functional demands made at different sites. In the present study, GAG content was highest in the constantly loaded central areas of the joint surfaces. In contrast, collagen content and HP crosslinks were higher in areas intermittently subjected to peak loading which suggests

  11. Increasing lateral tibial slope: is there an association with articular cartilage changes in the knee?

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Nasir; Shepel, Michael; Leswick, David A.; Obaid, Haron [University of Saskatchewan, Department of Medical Imaging, Royal University Hospital, and College of Medicine, Saskatoon, Saskatchewan (Canada)

    2014-04-15

    The geometry of the lateral tibial slope (LTS) plays an important role in the overall biomechanics of the knee. Through this study, we aim to assess the impact of LTS on cartilage degeneration in the knee. A retrospective analysis of 93 knee MRI scans (1.5 T or 3 T) for patients aged 20-45 years with no history of trauma or knee surgery, and absence of internal derangement. The LTS was calculated using the circle method. Chondropathy was graded from 0 (normal) to 3 (severe). Linear regression analysis was used for statistical analysis (p < 0.05). In our cohort of patients, a statistically significant association was seen between increasing LTS and worsening cartilage degenerative changes in the medial patellar articular surface and the lateral tibial articular surface (p < 0.05). There was no statistically significant association between increasing LTS and worsening chondropathy of the lateral patellar, medial trochlea, lateral trochlea, medial femoral, lateral femoral, and medial tibial articular surfaces. Our results show a statistically significant association between increasing LTS and worsening cartilage degenerative changes in the medial patella and the lateral tibial plateau. We speculate that increased LTS may result in increased femoral glide over the lateral tibial plateau with subsequent increased external rotation of the femur predisposing to patellofemoral articular changes. Future arthroscopic studies are needed to further confirm our findings. (orig.)

  12. Tissue Engineering Based Therapy for Articular Cartilage Defects - A New Approach

    Directory of Open Access Journals (Sweden)

    Abraham S

    2007-01-01

    Full Text Available Background: Articular cartilage, the load-bearing tissue in diarthrodial joints, when damaged due to trauma could lead to osteoarthritis. At present Autologous Cartilage Implantation is an established method in which patients own chondrocytes are isolated and then implanted after in vitro expansion over the affected area with bovine or porcine collagen matrix. This procedure results in more of Collagen Type I during in vitro expansion, which eventually becomes fibrocartilage. Also it requires growth factors. We have in this study tried growing human Chondrocytes without growth factors using synthetic scaffolds to grow more Collagen Type II Materials and Methods: Human cartilage specimens were harvested through arthroscopy from the non-weight bearing area of the knee joint from 13 patients who underwent surgical procedures of the knee joint after getting their informed consent. The tissues were transported in saline taking 1 hour to laboratory and subjected to digestion with Collagenase type II for 16~18 Hrs. The chondrocyte cells obtained after dissociation were divided into two groups for culture. Gr. I were embedded in a Thermogelation polymer (TGP and Gr. II in basal culture media (DMEM + Ascorbic Acid without using any growth factors. The Group II cells were viable only for 4 weeks and then started degenerating. The TGP-Chondrocytes scaffolds were grown for 16 weeks and the specimens were harvested at 4, 8, 12 and 16-week intervals and their morphology and molecular characteristics were studied by H&E staining, S-100 protein analysis and RT-PCR.Results: Human chondrocytes could be cultured in both TGP (group I and Basal culture media (group II. The Gr. I cells were viable upto the 16th week while the Group II chondrocytes started degenerating after the 4 week. Both the groups were proven positive for S-100 protein, a Chondrocyte specific marker protein; Gr. II specimens after 4 weeks, and Gr. I specimens after 4, 8, 12 and 16 weeks. RT

  13. A Novel Model for the Mass Transfer of Articular Cartilage: Rolling Depression Load Device

    Science.gov (United States)

    Fan, Zhenmin; Zhang, Chunqiu; Liu, Haiying; Xu, Baoshan; Li, Jiang; Gao, Lilan

    The mass transfer is one of important aspects to maintain the physiological activity proper of tissue, specially, cartilage cannot run without mechanical environment. The mechanical condition drives nutrition in and waste out in the cartilage tissue, the change of this process plays a key role for biological activity. Researchers used to adopt compression to study the mass transfer in cartilage, here we firstly establish a new rolling depression load (RDL) device, and also put this device into practice. The device divided into rolling control system and the compression adjusting mechanism. The rolling control system makes sure the pure rolling and uniform speed of roller applying towards cultured tissue. The compression adjusting mechanism can realize different compressive magnitudes and uniform compression. Preliminary test showed that rolling depression load indeed enhances the process of mass transfer articular cartilage.

  14. Freeze-thaw treatment effects on the dynamic mechanical properties of articular cartilage

    Directory of Open Access Journals (Sweden)

    Muldrew Ken

    2010-10-01

    Full Text Available Abstract Background As a relatively non-regenerative tissue, articular cartilage has been targeted for cryopreservation as a method of mitigating a lack of donor tissue availability for transplant surgeries. In addition, subzero storage of articular cartilage has long been used in biomedical studies using various storage temperatures. The current investigation studies the potential for freeze-thaw to affect the mechanical properties of articular cartilage through direct comparison of various subzero storage temperatures. Methods Both subzero storage temperature as well as freezing rate were compared using control samples (4°C and samples stored at either -20°C or -80°C as well as samples first snap frozen in liquid nitrogen (-196°C prior to storage at -80°C. All samples were thawed at 37.5°C to testing temperature (22°C. Complex stiffness and hysteresis characterized load resistance and damping properties using a non-destructive, low force magnitude, dynamic indentation protocol spanning a broad loading rate range to identify the dynamic viscoelastic properties of cartilage. Results Stiffness levels remained unchanged with exposure to the various subzero temperatures. Hysteresis increased in samples snap frozen at -196°C and stored at -80°C, though remained unchanged with exposure to the other storage temperatures. Conclusions Mechanical changes shown are likely due to ice lens creation, where frost heave effects may have caused collagen damage. That storage to -20°C and -80°C did not alter the mechanical properties of articular cartilage shows that when combined with a rapid thawing protocol to 37.5°C, the tissue may successfully be stored at subzero temperatures.

  15. Leptin in osteoarthritis: Focus on articular cartilage and chondrocytes.

    Science.gov (United States)

    Scotece, Morena; Mobasheri, Ali

    2015-11-01

    Osteoarthritis (OA) is a complex joint disorder with a number of underlying physical, biochemical, biomechanical and genetic causes. Obesity is considered to be one of the major risk factors for the development and progression of OA. It actively contributes to the inflammatory status and to cartilage degradation in the OA joints. Recent data suggests that metabolic factors produced by white adipose tissue, such as leptin, may provide a mechanistic link between obesity and OA, providing an explanation for the high prevalence of OA among obese and over-weight individuals. The unbalanced production of catabolic and anabolic mediators by chondrocytes, the only cell type present in cartilage, determines cartilage degradation, which is the central pathological feature of OA. Evidence is accumulating to support a key role for leptin in the pathogenesis and/or progression of OA. The goal of this focused review is to summarize the current knowledge on the role of leptin in OA with particular emphasis on the effects of this adipokine in cartilage and chondrocyte pathophysiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Delayed Gadolinium-Enhanced Magnetic Resonance Imaging (dGEMRIC) of Hip Joint Cartilage: Better Cartilage Delineation after Intra-Articular than Intravenous Gadolinium Injection

    DEFF Research Database (Denmark)

    Boesen, M.; Jensen, K.E.; Quistgaard, E.

    2006-01-01

    PURPOSE: To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. MATERIAL AND METHODS: In 10 patients (50% males, mean age 58......: The dGEMRIC MRI method markedly improved delineation of hip joint cartilage compared to non-enhanced MRI. The i.a. Gd-DTPA provided the best cartilage delineation. dGEMRIC is a clinically applicable MRI method that may improve identification of early subtle cartilage damage and the accuracy of volume...... measurements of hip joint cartilage....

  17. Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular cartilage chondrocytes ameliorates osteoarthritis development.

    Science.gov (United States)

    Prasadam, Indira; Akuien, Akoy; Friis, Thor E; Fang, Wei; Mao, Xinzhan; Crawford, Ross W; Xiao, Yin

    2018-01-01

    Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.

  18. Helium ion microscopy for high-resolution visualization of the articular cartilage collagen network.

    Science.gov (United States)

    Vanden Berg-Foels, W S; Scipioni, L; Huynh, C; Wen, X

    2012-05-01

    The articular cartilage collagen network is an important research focus because network disruption results in cartilage degeneration and patient disability. The recently introduced helium ion microscope (HIM), with its smaller probe size, longer depth of field and charge neutralization, has the potential to overcome the inherent limitations of electron microscopy for visualization of collagen network features, particularly at the nanoscale. In this study, we evaluated the capabilities of the helium ion microscope for high-resolution visualization of the articular cartilage collagen network. Images of rabbit knee cartilage were acquired with a helium ion microscope; comparison images were acquired with a field emission scanning electron microscope (FE-SEM) and a transmission electron microscope (TEM). Sharpness of example high-resolution helium ion microscope and field emission scanning electron microscope images was quantified using the 25-75% rise distance metric. The helium ion microscope was able to acquire high-resolution images with unprecedented clarity, with greater sharpness and three-dimensional-like detail of nanoscale fibril morphologies and fibril connections, in samples without conductive coatings. These nanoscale features could not be resolved by field emission scanning electron microscopy, and three-dimensional network structure could not be visualized with transmission electron microscopy. The nanoscale three-dimensional-like visualization capabilities of the helium ion microscope will enable new avenues of investigation in cartilage collagen network research. © 2012 The Authors Journal of Microscopy © 2012 Royal Microscopical Society.

  19. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    Science.gov (United States)

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  20. Inhibition of glycosaminoglycan incorporation influences collagen network formation during cartilage matrix production

    NARCIS (Netherlands)

    Bastiaansen-Jenniskens, Y.M.; Koevoet, W.; Jansen, K.M.B.; Verhaar, J.A.N.; Groot, J. de; Vanosch, G.J.V.M.

    2009-01-01

    To understand cartilage degenerative diseases and improve repair procedures, we investigate the influence of glycosaminoglycans (GAGs) on cartilage matrix biochemistry and functionality. Bovine articular chondrocytes were cultured in alginate beads with(out) para-nitrophenyl-beta-d-xyloside (PNPX)

  1. T2* mapping for articular cartilage assessment: principles, current applications, and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Hesper, Tobias; Bittersohl, Daniela; Krauspe, Ruediger; Zilkens, Christoph [University Duesseldorf, Department of Orthopaedics Medical Faculty, Duesseldorf (Germany); Hosalkar, Harish S. [Center of Hip Preservation and Children' s Orthopaedics, San Diego, CA (United States); Welsch, Goetz H. [Medical University of Vienna, MR Center, Department of Radiology, Vienna (Austria); Bittersohl, Bernd [University Duesseldorf, Department of Orthopaedics Medical Faculty, Duesseldorf (Germany); Heinrich-Heine University, Medical School, Department of Orthopaedics, Duesseldorf (Germany)

    2014-10-15

    With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation - without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented. (orig.)

  2. Computational biomechanics of articular cartilage of human knee joint: effect of osteochondral defects.

    Science.gov (United States)

    Shirazi, R; Shirazi-Adl, A

    2009-11-13

    Articular cartilage and its supporting bone functional conditions are tightly coupled as injuries of either adversely affects joint mechanical environment. The objective of this study was set to quantitatively investigate the extent of alterations in the mechanical environment of cartilage and knee joint in presence of commonly observed osteochondral defects. An existing validated finite element model of a knee joint was used to construct a refined model of the tibial lateral compartment including proximal tibial bony structures. The response was computed under compression forces up to 2000 N while simulating localized bone damage, cartilage-bone horizontal split, bone overgrowth and absence of deep vertical collagen fibrils. Localized tibial bone damage increased overall joint compliance and substantially altered pattern and magnitude of contact pressures and cartilage strains in both tibia and femur. These alterations were further exacerbated when bone damage was combined with base cartilage split and absence of deep vertical collagen fibrils. Local bone boss markedly changed contact pressures and strain patterns in neighbouring cartilage. Bone bruise/fracture and overgrowth adversely perturbed the homeostatic balance in the mechanical environment of articulate cartilage surrounding and opposing the lesion as well as the joint compliance. As such, they potentially contribute to the initiation and development of post-traumatic osteoarthritis.

  3. Effect of articular cartilage proteoglycan depletion on high frequency ultrasound backscatter.

    Science.gov (United States)

    Pellaumail, B; Watrin, A; Loeuille, D; Netter, P; Berger, G; Laugier, P; Saïed, A

    2002-07-01

    To study the effect of variations of articular cartilage proteoglycans (PG) on high-frequency ultrasound backscatter. The study was performed on patellar cartilages of immature and mature rats (N=36). The variation of PG content was induced by enzyme digestion. Control and treated cartilages were explored in vitro using a 55MHz scanning acoustic microscopy, then assessed by histology for the fibrillar collagen organization analysis. The variations of proteoglycan and collagen content were evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radio-frequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). Although hyaluronidase treatment of immature and mature cartilages removed approximately 50% of the proteoglycans, the echogenicity level of ultrasound images of degraded cartilages was similar to that of controls. IRC and AIB parameters did not significantly vary. Histologic sections of degraded cartilage displayed no change in collagen fiber organization. The thickness mean values measured by ultrasound in PG-depleted groups were significantly higher than in controls, whereas no significant difference in thickness was detected by histological measurement. The increase in cartilage thickness may potentially be explained by a decrease of speed of sound in PG-depleted cartilages that is more likely subsequent to an increase of water content. Current results indicate that PG depletion has no significant effect on high frequency ultrasound backscattered from rat patellar cartilage. Ultrasound may provide information about variations of PG content via speed of sound measurement. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

  4. Proteomic analysis of human articular cartilage: identification of differentially expressed proteins in knee osteoarthritis.

    Science.gov (United States)

    Guo, Dunming; Tan, Wenfeng; Wang, Fang; Lv, Zheng; Hu, Jun; Lv, Tianrun; Chen, Qun; Gu, Xiaoyuan; Wan, Bing; Zhang, Zhongnan

    2008-07-01

    The mechanisms underlying the development of age related osteoarthritis (OA) remain unclear. To better understand the pathogenesis of OA and the molecular basis of progressive destruction of articular cartilage in OA, we compared the proteome of OA cartilage with that of normal cartilage. After removal of proteoglycans and collagens, proteins extracted from either normal or OA knee joint cartilage were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins in OA cartilage were chosen to be further identified by linear ion trap-Fourier transform ion cyclotron resonance mass spectrometry (LTQ-FT/MS). A total of 1436+/-49 or 1472+/-7 protein spots were resolved by 2-DE of normal or OA cartilage extractions, respectively. Sixteen spots from OA cartilage samples were found to have statistically significant changes in the amount of protein compared with normal samples. Of 16 spots, the identities of 14 proteins were unambiguously determined by LTQ-FT/MS. These OA associated proteins fell into five groups, including glycolysis and energy production (ADH, ADK, ENOA, KPYM and FR), signaling (ANNX-I, PEBP and TUB), Redox (PRDX3 and SODM), and cartilage matrix (COLL-I and COLL-VI). Interestingly, two novel RING (Really Interesting New Gene) domain-containing proteins, RF, Zn-RF, were identified, suggesting novel pathways of cartilage protein regulation. This study shows that 2-DE followed by LTQ-FT/MS can be successfully used to characterize the proteome of cartilage without in vitro culturing which could obfuscate physiological differences. The definition of unique OA-associated proteins described here provides significant mechanistic insights into OA by corroborating previously suggested mechanisms and by defining unique players with roles yet to be defined in disease pathogenesis.

  5. Effect of homologous synovial membrane on adult human articular cartilage in organ culture, and failure to influence it with D-penicillamine.

    OpenAIRE

    Jacoby, R K

    1980-01-01

    Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage + homologous synovium; (4) cartilage, synovium, and D-penicillamine. The hexosamines and hexuronic acid were measured in the cartilage explants and in the medium. The quantity re...

  6. Accuracy evaluation of automatic quantification of the articular cartilage surface curvature from MRI

    DEFF Research Database (Denmark)

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F

    2007-01-01

    RATIONALE AND OBJECTIVES: To study the articular cartilage surface curvature determined automatically from magnetic resonance (MR) knee scans, evaluate accuracy of the curvature estimates on digital phantoms, and an evaluation of their potential as disease markers for different stages of osteoart......RATIONALE AND OBJECTIVES: To study the articular cartilage surface curvature determined automatically from magnetic resonance (MR) knee scans, evaluate accuracy of the curvature estimates on digital phantoms, and an evaluation of their potential as disease markers for different stages...... for intersubject comparisons. Digital phantoms were created to establish the accuracy of the curvature estimation methods. RESULTS: A comparison of the two curvature estimation methods to ground truth yielded absolute pairwise differences of 1.1%, and 4.8%, respectively. The interscan reproducibility for the two...

  7. Aberrant Calreticulin Expression in Articular Cartilage of Dio2 Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Nils Bomer

    Full Text Available To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis.Previously generated microarray-data (Illumina MouseWG-6 v2 of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5 were applied to assess the direct effect of differential Calr expression on cartilage deposition.Differential expression analyses of articular cartilage of Dio2-/- (N = 9 and wild-type-mice (N = 11 while applying a cutoff threshold (P |1,5| resulted in 1 probe located in Calreticulin (Calr that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044. Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition.We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity.

  8. POSSIBILITIES OF CURRENT CELLULAR TECHNOLOGIES FOR ARTICULAR CARTILAGE REPAIR (ANALYTICAL REVIEW

    Directory of Open Access Journals (Sweden)

    M. S. Bozhokin

    2016-01-01

    Full Text Available Despite a wide variety of surgical procedures utilized in clinical practice for treatment of articular cartilage lesions, the search for other options of articular reconstruction remains a relevant and open issue at the current stage of medicine and biotechnologies development. The recent years demonstrated a strong belief in cellular methods of hyaline cartilage repair such as implantation of autologous chondrocytes (ACI or cultures of mesenchymal stem cells (MSC including techniques for genetic modification of cells.The purpose of presented review is to summarize the published scientific data on up to date results of perspective cellular technologies for articular cartilage repair that are being developed. Autologous chondrocyte transplantation originally performed by Swedish researchers in 1987 is considered the first clinically applied technique for restoration of hyaline cartilage using cellular technologies. However, the transplanted cell culture featured low proliferative capacity and inability to form a regenerate resistant to high physical activity. Another generation of methods originated at the turn of the century utilized mesenchymal stem cells instead of autologous chondrocytes. Preparation of MSCs is a less invasive procedure compared to chondrocytes harvesting and the culture is featured by a higher proliferative ability. Researchers use various biodegradable carriers (matrices to secure cell fixation. Despite good clinical mid-term outcomes the transplanted tissue-engineering structures deteriorate with time due to cellular de-differentiation. Next generation of techniques being currently under pre-clinical studies is featured by the preliminary chondrogenic modification of transplanted cell culture. Usage of various growth factors, modified cell product and gene-activated matrices allow to gain a stable regulatory and key proteins synthesis and achieve a focused influence on regenerate's chondrogenic proliferation and in result

  9. Semi-automated International Cartilage Repair Society scoring of equine articular cartilage lesions in optical coherence tomography images.

    Science.gov (United States)

    Te Moller, N C R; Pitkänen, M; Sarin, J K; Väänänen, S; Liukkonen, J; Afara, I O; Puhakka, P H; Brommer, H; Niemelä, T; Tulamo, R-M; Argüelles Capilla, D; Töyräs, J

    2017-07-01

    Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. Validation study using equine cadaver tissue. Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom-made software was developed for semi-automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi-automatically by five observers, and levels of inter- and intraobserver agreement were calculated. Subsequently, OCT-based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82). When semi-automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology-based scores from matching regions of interest agreed better with visual OCT-based scoring than with semi-automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score. Images were obtained from cadavers. Semi-automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer-dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi-automated ICRS scoring. In addition, studies on in vivo applications are required. © 2016 EVJ Ltd.

  10. Influence of Proteoglycan on Time-Dependent Mechanical Behaviors of Articular Cartilage under Constant Total Compressive Deformation

    Science.gov (United States)

    Murakami, Teruo; Sakai, Nobuo; Sawae, Yoshinori; Tanaka, Koji; Ihara, Maki

    Articular cartilage has biphasic property based on high water content. It is generally believed that the proteoglycan supports the compressive load, but the detailed loading mechanism has not yet been clarified. In this study, first we observed the changes in compressive stress and strain of articular cartilage under constant total compressive deflection. We evaluated the changes in modulus of elasticity, which was estimated from the stress-strain relation in equilibrium state. To examine the role of proteoglycan in compressed articular cartilage, we compared the time-dependent viscoelastic behaviors in both the intact cartilage and the cartilage treated with chondoroitinase ABC under constant total compressive deformation. We could confirm that the peak stress after compression and the modulus of elasticity at equilibrium were reduced after the digestion of proteoglycan. Next, we observed the changes in local strain in both articular cartilage specimens with and without chondroitinase treatment by monitoring the position of stained chondrocyte in the confocal laser scanning microscope. These visualized images indicated that the local strain changed time-dependently and depth-dependently. The digested cartilage showed the quicker change in movement and larger thinning in surface layer than the intact cartilage. These results indicate that the proteoglycan contributes to the compressive load-carrying capacity and controls the permeability.

  11. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roel

    2015-01-01

    Purpose: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. Methods: Explants of porcine

  12. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roelof

    PURPOSE: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. METHODS: Explants of porcine

  13. Joint degeneration following meniscal allograft transplantation in a canine model: mechanical properties and semiquantitative histology of articular cartilage.

    Science.gov (United States)

    Elliott, Dawn M; Jones, Relief; Setton, Lori A; Scully, Sean P; Vail, T Parker; Guilak, Farshid

    2002-03-01

    This study examined the hypothesis that meniscal allograft transplantation serves a "chondroprotective" role and prevents the histological and biomechanical changes of the articular cartilage following meniscectomy. Skeletally mature mongrel dogs underwent total medial meniscectomy and received either a fresh meniscal allograft ( n=10) or no further treatment ( n=10). Semiquantitative histology and biomechanical analysis of the femoral articular cartilage was used to assess cartilage pathology 12 weeks following surgery. Histological analysis showed significant changes in cartilage structure that did not differ between the meniscectomy and allograft transplantation groups. Similarly, the tensile modulus of the surface zone cartilage was significantly lower than that in unoperated controls following either meniscectomy or allograft transplantation. A significant correlation was observed between the biomechanical and histological changes, suggesting that degenerative changes in cartilage structure and mechanical function are interrelated. Our findings do not support the hypothesis that meniscal allograft transplantation provides chondroprotection of the femoral condyle and also suggest that it does not lead to increased degenerative changes.

  14. The importance of bicarbonate and nonbicarbonate buffer systems in batch and continuous flow bioreactors for articular cartilage tissue engineering.

    Science.gov (United States)

    Khan, Aasma A; Surrao, Denver C

    2012-05-01

    In cartilage tissue engineering an optimized culture system, maintaining an appropriate extracellular environment (e.g., pH of media), can increase cell proliferation and extracellular matrix (ECM) accumulation. We have previously reported on a continuous-flow bioreactor that improves tissue growth by supplying the cells with a near infinite supply of medium. Previous studies have observed that acidic environments reduce ECM synthesis and chondrocyte proliferation. Hence, in this study we investigated the combined effects of a continuous culture system (bioreactor) together with additional buffering agents (e.g., sodium bicarbonate [NaHCO₃]) on cartilaginous tissue growth in vitro. Isolated bovine chondrocytes were grown in three-dimensional cultures, either in static conditions or in a continuous-flow bioreactor, in media with or without NaHCO₃. Tissue constructs cultivated in the bioreactor with NaHCO₃-supplemented media were characterized with significantly increased (pbioreactor with NaHCO₃-supplemented media were significantly thicker than all other constructs (pTissue outgrowth was negligible in all other culturing conditions. Thus this study demonstrates the advantage of employing a continuous flow bioreactor coupled with NaHCO₃ supplemented media for articular cartilage tissue engineering.

  15. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    Science.gov (United States)

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  16. FUNCTIONS OF THE mTOR SIGNALING PATHWAY IN NORMAL ARTICULAR CARTILAGE CHONDROCYTES AND IN OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    E. V. Chetina

    2016-01-01

    Full Text Available Osteoarthritis  (OA is a chronic disease associated with pain, stiffness, limited mobility and joint inflammation, as well as articular cartilage destruction.  Recent studies have shown the importance  of chondrocyte  differentiation (hypertrophy as one of the mechanisms  of cartilage degradation in OA. This suggests that chondrocyte  metabolism undergoes the profound changes during cartilage resorption,  which are due to dysregulation of cell function. One of the major cellular metabolic regulators is the protein mTOR (mechanistic target of rapamycin that controls cell growth, proliferation, protein biosynthesis and integrates extracellular signals from growth factors and hormones with amino acid availability and intracellular energy status. The importance  of mTOR activity for articular cartilage destruction  in OAis confirmed by significant changes in the work of mTOR regulatory network that involves multiple intracellular (growth factors, adenosine triphosphate, oxygen availability, and autophagy and extracellular (glucose, amino acids, lipids, and hexosamine signals. Moreover, the altered expression of the mTOR gene in the blood of patients with OA is associated with either increased pain or synovitis, which indicates that there is a strong metabolic heterogeneity in patients with OA and a need for a differentiated therapeutic  approach. The above problems are discussed in this review.

  17. [Technological aspects of regenerative medicine and tissue engineering of articular cartilage].

    Science.gov (United States)

    Pörtner, R; Meenen, N M

    2010-12-01

    The main problem in the treatment of orthopaedic joint-surface defects will be solved by tissue engineering of cartilage implants. Entire biological osteochondral implants can be grown from autologous cells of the patient. The nutrition of articular cartilage is by diffusion only. Therefore the chondrocyte as the unique cell type is perfectly dedicated to the tissue culture approach. Engineering techniques of bioreactors are prerequisite for these biological and medical solutions. With our tissue engineering project for the generation of osteochondral constructs we demonstrate possibilities and characteristics of bioreactors for the modification of cell culture techniques and mechanical conditioning of cartilage tissue for fully operable implants. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, J.; Treadwell, B.V.; Mankin, H.J.

    1984-01-01

    Incorporation of radioactive precursors into macromolecules was studied with human normal and osteoarthritic articular cartilage organ culture. Analysis of the salt extracted matrix components separated by cesium chloride buoyant density gradient centrifugation showed an increase in the specific activities of all gradient fractions prepared from the osteoarthritic cartilage. Further analysis of these fractions showed the osteoarthritic cartilage contained 5 times as much sulfate incorporated into proteoglycans, and an even greater amount of 3H-glucosamine incorporated into material sedimenting to the middle of the gradient. Greater than half of this radioactive middle fraction appears to be hyaluronate, as judged by the position it elutes from a DEAE column and its susceptibility to hyaluronidase digestion. This study supports earlier findings showing increased rates of macromolecular synthesis in osteoarthritis, and in addition, an even greater synthetic rate for hyaluronic acid is demonstrated.

  19. Enzymatic digestion of articular cartilage results in viscoelasticity changes that are consistent with polymer dynamics mechanisms

    Directory of Open Access Journals (Sweden)

    June Ronald K

    2009-11-01

    Full Text Available Abstract Background Cartilage degeneration via osteoarthritis affects millions of elderly people worldwide, yet the specific contributions of matrix biopolymers toward cartilage viscoelastic properties remain unknown despite 30 years of research. Polymer dynamics theory may enable such an understanding, and predicts that cartilage stress-relaxation will proceed faster when the average polymer length is shortened. Methods This study tested whether the predictions of polymer dynamics were consistent with changes in cartilage mechanics caused by enzymatic digestion of specific cartilage extracellular matrix molecules. Bovine calf cartilage explants were cultured overnight before being immersed in type IV collagenase, bacterial hyaluronidase, or control solutions. Stress-relaxation and cyclical loading tests were performed after 0, 1, and 2 days of incubation. Results Stress-relaxation proceeded faster following enzymatic digestion by collagenase and bacterial hyaluronidase after 1 day of incubation (both p ≤ 0.01. The storage and loss moduli at frequencies of 1 Hz and above were smaller after 1 day of digestion by collagenase and bacterial hyaluronidase (all p ≤ 0.02. Conclusion These results demonstrate that enzymatic digestion alters cartilage viscoelastic properties in a manner consistent with polymer dynamics mechanisms. Future studies may expand the use of polymer dynamics as a microstructural model for understanding the contributions of specific matrix molecules toward tissue-level viscoelastic properties.

  20. Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage

    Science.gov (United States)

    2013-01-01

    Introduction Adipose-derived stem cells (ADSCs) have been isolated, expanded, and applied in the treatment of many diseases. ADSCs have also been used to treat injured articular cartilage. However, there is controversy regarding the treatment efficiency. We considered that ADSC transplantation with activated platelet-rich plasma (PRP) may improve injured articular cartilage compared with that of ADSC transplantation alone. In this study, we determined the role of PRP in ADSC transplantation to improve the treatment efficiency. Methods ADSCs were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage. Results PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs. Conclusion Pretreatment of ADSCs with PRP is a simple method to efficiently apply ADSCs in cartilage regeneration. This study provides an important step toward the use of autologous ADSCs in the treatment of injured articular cartilage. PMID:23915433

  1. Assessment of articular cartilage and subchondral bone using EPIC-microCT in Labrador retrievers with incipient medial coronoid disease.

    Science.gov (United States)

    Lau, S F; Wolschrijn, C F; Siebelt, M; Vernooij, J C M; Voorhout, G; Hazewinkel, H A W

    2013-10-01

    The aetiopathogenesis of medial coronoid disease (MCD) remains obscure, despite its high prevalence. The role of changes to subchondral bone or articular cartilage is much debated. Although there is evidence of micro-damage to subchondral bone, it is not known whether this is a cause or a consequence of MCD, nor is it known whether articular cartilage is modified in the early stages of the disease. The aim of the present study was to use equilibrium partitioning of an ionic contrast agent with micro-computed tomography (microCT) to investigate changes to both the articular cartilage and the subchondral bone of the medial coronoid processes (MCP) of growing Labrador retrievers at an early stage of the disease and at different bodyweights. Of 14 purpose-bred Labrador retrievers (15-27 weeks), six were diagnosed with bilateral MCD and one was diagnosed with unilateral MCD on the basis of microCT studies. The mean X-ray attenuation of articular cartilage was significantly higher in dogs with MCD than in dogs without MCD (Pdogs, the mean X-ray attenuation of articular cartilage was significantly higher at the lateral (P0.05), indicating that subchondral bone density is not affected in early MCD. This study demonstrated that cartilage matrix and not subchondral bone density is affected in the early stages of MCD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Articular cartilage thickness and glycosaminoglycan distribution in the young canine knee joint after remobilization of the immobilized limb.

    Science.gov (United States)

    Kiviranta, I; Tammi, M; Jurvelin, J; Arokoski, J; Säämänen, A M; Helminen, H J

    1994-03-01

    The recovery of articular cartilage from atrophy induced by joint immobilization was investigated in immature dogs. In a previous study, we showed that 11 weeks of immobilization of the knee (stifle) joint of young dogs reduced the concentration of articular cartilage glycosaminoglycans (GAGs) by 13-47%. In the present study, right hindlimbs from six female beagles were immobilized for 11 weeks, as in the previous study, and then were remobilized for 15 weeks. Cartilage from the knee joint was compared with cartilage from nonimmobilized knees of eight age-matched control beagles. Histological samples taken from 11 different locations of the knee joint were stained with safranin O, and microspectrophotometry was used to demonstrate distribution of GAGs in the tissue. After remobilization, GAG concentration was restored in the patellofemoral region and tibial condyles. On the summits of the femoral condyles, and especially at the periphery of the femoral condyles, GAG concentration remained 8-26% less than the control values. On the summits, the thickness of the uncalcified cartilage was as much as 15% less than in the age-matched controls. Consequently, the changes induced by unloading were reversible to a great extent, but a full restoration of articular cartilage was not obtained at all sites of the knee joint within the 15 weeks of remobilization. Immobilization of the skeletally immature joint therefore may affect the development of articular cartilage in such a way that very slow recovery or permanent alterations are induced.

  3. Correlation between polarization sensitive optical coherence tomography and SHG microscopy in articular cartilage

    Science.gov (United States)

    Zhou, Xin; Ju, Myeong Jin; Huang, Lin; Tang, Shuo

    2017-02-01

    Polarization-sensitive optical coherence tomography (PS-OCT) and second harmonic generation (SHG) microscopy are two imaging modalities with different resolutions, field-of-views (FOV), and contrasts, while they both have the capability of imaging collagen fibers in biological tissues. PS-OCT can measure the tissue birefringence which is induced by highly organized fibers while SHG can image the collagen fiber organization with high resolution. Articular cartilage, with abundant structural collagen fibers, is a suitable sample to study the correlation between PS-OCT and SHG microscopy. Qualitative conjecture has been made that the phase retardation measured by PS-OCT is affected by the relationship between the collagen fiber orientation and the illumination direction. Anatomical studies show that the multilayered architecture of articular cartilage can be divided into four zones from its natural surface to the subchondral bone: the superficial zone, the middle zone, the deep zone, and the calcified zone. The different zones have different collagen fiber orientations, which can be studied by the different slopes in the cumulative phase retardation in PS-OCT. An algorithm is developed based on the quantitative analysis of PS-OCT phase retardation images to analyze the microstructural features in swine articular cartilage tissues. This algorithm utilizes the depth-dependent slope changing of phase retardation A-lines to segment structural layers. The results show good consistency with the knowledge of cartilage morphology and correlation with the SHG images measured at selected depth locations. The correlation between PS-OCT and SHG microscopy shows that PS-OCT has the potential to analyze both the macro and micro characteristics of biological tissues with abundant collagen fibers and other materials that may cause birefringence.

  4. Topographical variation of the elastic properties of articular cartilage in the canine knee.

    Science.gov (United States)

    Jurvelin, J S; Arokoski, J P; Hunziker, E B; Helminen, H J

    2000-06-01

    Equilibrium response of articular cartilage to indentation loading is controlled by the thickness (h) and elastic properties (shear modulus, mu, and Poisson's ratio, nu) of the tissue. In this study, we characterized topographical variation of Poisson's ratio of the articular cartilage in the canine knee joint (N=6). Poisson's ratio was measured using a microscopic technique. In this technique, the shape change of the cartilage disk was visualized while the cartilage was immersed in physiological solution and compressed in unconfined geometry. After a constant 5% axial strain, the lateral strain was measured during stress relaxation. At equilibrium, the lateral-to-axial strain ratio indicates the Poisson's ratio of the tissue. Indentation (equilibrium) data from our prior study (Arokoski et al., 1994. International Journal of Sports Medicine 15, 254-260) was re-analyzed using the Poisson's ratio results at the test site to derive values for shear and aggregate moduli. The lowest Poisson's ratio (0.070+/-0.016) located at the patellar surface of femur (FPI) and the highest (0.236+/-0.026) at the medial tibial plateau (TMI). The stiffest cartilage was found at the patellar groove of femur (micro=0.964+/-0.189MPa, H(a)=2.084+/-0. 409MPa) and the softest at the tibial plateaus (micro=0.385+/-0. 062MPa, H(a)=1.113+/-0.141MPa). Comparison of the mechanical results and the biochemical composition of the tissue (Jurvelin et al., 1988. Engineering in Medicine 17, 157-162) at the matched sites of the canine knee joint indicated a negative correlation between the Poisson's ratio and collagen-to-PG content ratio. This is in harmony with our previous findings which suggested that, in unconfined compression, the degree of lateral expansion in different tissue zones is related to collagen-to-PG ratio of the zone.

  5. Synovial fluid biomarker levels predict articular cartilage damage following complete medial meniscectomy in the canine knee.

    Science.gov (United States)

    Carlson, Cathy S; Guilak, Farshid; Vail, Thomas P; Gardin, Jean F; Kraus, Virginia B

    2002-01-01

    The purposes of this study were to document the histological changes present in the tibial plateaus 12 weeks after complete medial meniscectomy in dogs and to determine if synovial lavage fluid biomarker levels are predictive of the severity of joint damage. Twelve adult dogs underwent complete unilateral medial meniscectomy and synovial lavage fluid biomarker levels, including cartilage oligomeric matrix protein (COMP), keratan sulfate (5D4). 3B3(-), and 3B3(+), were measured serially at 4-week intervals. The dogs were euthanized 12 weeks after surgery and each medial and lateral tibial plateau from the meniscectomized and contralateral knees was graded histologically. Histological data were analyzed using principal components analysis, which resulted in 4 factors that explained 70% of the variation in the data. Factor 2 (weighted most heavily by subchondral bone thickness) and Factor 3 (representative of articular cartilage damage) were significantly affected by compartmental site (P knee, and Factor 3 was significantly higher in this site than in the medial tibial plateau of the contralateral knee (P canine meniscectomy as surrogate measures of articular cartilage damage.

  6. Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee.

    Science.gov (United States)

    Fischenich, Kristine M; Button, Keith D; Coatney, Garrett A; Fajardo, Ryan S; Leikert, Kevin M; Haut, Roger C; Haut Donahue, Tammy L

    2015-01-21

    The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post-impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (ppermeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p=0.036). In both meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post-injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. In-laboratory diffraction-enhanced X-ray imaging for articular cartilage.

    Science.gov (United States)

    Muehleman, Carol; Fogarty, Daniel; Reinhart, Benjamin; Tzvetkov, Tochko; Li, Jun; Nesch, Ivan

    2010-07-01

    The loss of articular cartilage characteristic of osteoarthritis can only be diagnosed by joint space narrowing when conventional radiography is used. This is due to the lack of X-ray contrast of soft tissues. Whereas conventional radiography harnesses the X-ray attenuation properties of tissues, Diffraction Enhanced Imaging (DEI), a novel radiographic technique, allows the visualization of soft tissues simultaneous with calcified tissues by virtue of its ability to not only harness X-ray attenuation but also the X-ray refraction from tissue boundaries. Previously, DEI was dependent upon synchrotron X-rays, but more recently, the development of nonsynchrotron DEI units has been explored. These developments serve to elaborate the full potential of radiography. Here, we tested the potential of an in-laboratory DEI system, called Diffraction-Enhanced X-ray Imaging (DEXI), to render images of articular cartilage displaying varying degrees of degradation, ex vivo. DEXI allowed visualization of even early stages of cartilage degeneration such as surface fibrillation. This may be of eventual clinical significance for the diagnosis of early stages of degeneration, or at the very least, to visualize soft tissue degeneration simultaneous with bone changes. (c) 2010 Wiley-Liss, Inc.

  8. The effects of proteoglycan and type II collagen on T1rho relaxation time of articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Won Seok; Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja Young [Dept. of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-02-15

    To evaluate the effects of proteoglycan and type II collagen within articular cartilage on T1rho relaxation time of articular cartilage. This study was exempted by the institutional and animal review boards, and informed consent was not required. Twelve porcine patellae were assigned to three groups of control, trypsin-treated (proteoglycan-degraded), or collagenase-treated (collagen-degraded). The T1rho images were obtained with a 3 tesla magnetic resonance imaging scanner with a single loop coil. Statistical differences were detected by analysis of variance to evaluate the effects of the enzyme on T1rho relaxation time. Safranin-O was used to stain proteoglycan in the articular cartilage and immunohistochemical staining was performed for type II collagen. Mean T1rho values of the control, trypsin-treated, and collagenase-treated groups were 37.72 +/- 5.82, 57.53 +/- 8.24, and 45.08 +/- 5.31 msec, respectively (p < 0.001). Histology confirmed a loss of proteoglycan and type II collagen in the trypsin- and collagenase-treated groups. Degradation of proteoglycans and collagen fibers in the articular cartilage increased the articular cartilage T1rho value.

  9. Spatial and temporal changes of subchondral bone proceed to articular cartilage degeneration in rats subjected to knee immobilization.

    Science.gov (United States)

    Xu, Lei; Li, Zhe; Lei, Lei; Zhou, Yue-Zhu; Deng, Song-Yun; He, Yong-Bin; Ni, Guo-Xin

    2016-03-01

    This study was aimed to investigate the spatial and temporal changes of subchondral bone and its overlying articular cartilage in rats following knee immobilization. A total of 36 male Wistar rats (11-13 months old) were assigned randomly and evenly into 3 groups. For each group, knee joints in 6 rats were immobilized unilaterally for 1, 4, or 8 weeks, respectively, while the remaining rats were allowed free activity and served as external control groups. For each animal, femurs at both sides were dissected after sacrificed. The distal part of femur was examined by micro-CT. Subsequently, femoral condyles were collected for further histological observation and analysis. For articular cartilage, significant changes were observed only at 4 and 8 weeks of immobilization. The thickness of articular cartilage and chondrocytes numbers decreased with time. However, significant changes in subchondral bone were defined by micro-CT following immobilization in a time-dependent manner. Immobilization led to a thinner and more porous subchondral bone plate, as well as a reduction in trabecular thickness and separation with a more rod-like architecture. Changes in subchondral bone occurred earlier than in articular cartilage. More importantly, immobilization-induced changes in subchondral bone may contribute, at least partially, to changes in its overlying articular cartilage. © 2016 Wiley Periodicals, Inc.

  10. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Pengzhen Wang

    Full Text Available Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1 and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic

  11. Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo

    DEFF Research Database (Denmark)

    Madsen, S H; Sondergaard, B C; Jensen, Anne-Christine Bay

    2009-01-01

    OBJECTIVES: The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model. METHODS: Bovine articular cartilage...... and more than 3000% (p cartilage formation. The current developed...

  12. Enhanced regulatory gene expressions in the blood and articular cartilage of patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Elena Vasilyevna Chetina

    2012-01-01

    Full Text Available Objective: to study the expression ratio of the non-tissue specific regulatory genes mTOR, р21, ATG1, caspase 3, tumor necrosis factor-а (TNF-а, and interleukin-6 (IL-6, as well as matrix metalloproteinase 13 (MMP-13 and X type collagen (COL10A1, cartilage resorption-associated MMP13 and COL10A1 in the blood and knee articular cartilage in patients with rheumatoid arthritis (RA. Subjects and methods. Twenty-five specimens of the distal femoral articular cartilage condyles were studied in 15 RA patients (mean age 52.4+9.1 years after endoprosthetic knee joint replacement and in 10 healthy individuals (mean age 36.0+9.1 years included into the control group. Twenty-eight blood samples taken from 28 RA patients (aged 52+7.6 years prior to endoprosthetic knee joint replacement and 27 blood samples from healthy individuals (mean age 53.6+8.3 years; a control group were also analyzed. Real-time quantitative polymerase chain reaction was applied to estimate the expression of the mTOR, p21, ATG1, caspase 3, TNF-а, IL- 6, COL0A1, and MMP-13 genes. The levels of a protein equivalent in the p70-S6K(activated by mTOR, p21, and caspase 3 genes concerned was measured in the isolated lymphocyte lysates, by applying the commercially available ELISA kits. Total protein in the cell extracts was determined using the Bradford assay procedure. Results. The cartilage samples from patients with end-stage RA exhibited a significantly higher mTOR, ATG1, p21, TNFа, MMP-13, and COL10A1 gene expressions than did those from the healthy individuals. At the same time, IL6 gene expression was much lower than that in the control group. The expressions of the mTOR, ATG1, p21, TNFа, and IL 6 genes in the blood of RA patients were much greater than those in the donors. Caspase 3 expression did not differ essentially in the bloods of the patients with RA and healthy individuals. The bloods failed to show MMP-13 and COL10A1 expressions. High mTOR and p21 gene expressions were

  13. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis

    Science.gov (United States)

    Boyde, A; Davis, G R; Mills, D; Zikmund, T; Cox, T M; Adams, V L; Niker, A; Wilson, P J; Dillon, J P; Ranganath, L R; Jeffery, N; Jarvis, J C; Gallagher, J A

    2014-01-01

    High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. PMID:25132002

  15. Using Costal Chondrocytes to Engineer Articular Cartilage with Applications of Passive Axial Compression and Bioactive Stimuli.

    Science.gov (United States)

    Huwe, Le W; Sullan, Gurdeep K; Hu, Jerry C; Athanasiou, Kyriacos A

    2017-08-14

    Generating neocartilage with suitable mechanical integrity from a cell source that can circumvent chondrocyte scarcity is indispensable for articular cartilage regeneration strategies. Costal chondrocytes of the rib eliminate donor site morbidity in the articular joint, but it remains unclear how neocartilage formed from these cells responds to mechanical loading, especially if the intent is to use it in a load-bearing joint. In a series of three experiments, this study sought to determine efficacious parameters of passive axial compressive stimulation that would enable costal chondrocytes to synthesize mechanically robust cartilage. Experiment 1 determined a suitable time window for stimulation by its application during either the matrix synthesis phase, the maturation phase, or during both phases of the self-assembling process. The results showed that compressive stimulation at either time was effective in increasing instantaneous moduli by 92% and 87% in the synthesis and maturation phases, respectively. Compressive stimulation during both phases did not further improve properties beyond a one-time stimulation. The magnitude of passive axial compression was examined in Experiment 2 by applying 0, 3.3, 5.0, or 6.7 kPa stresses to the neocartilage. Unlike 6.7 kPa, both 3.3 and 5.0 kPa significantly increased neocartilage compressive properties by 42% and 48% over untreated controls, respectively. Experiment 3 examined how the passive axial compression regimen developed from the previous phases interacted with a bioactive regimen (transforming growth factor [TGF]-β1, chondroitinase ABC, and lysyl oxidase-like 2). Passive axial compression significantly improved the relaxation modulus compared with bioactive treatment alone. Furthermore, a combined treatment of compressive and bioactive stimulation improved the tensile properties of neocartilage 2.6-fold compared with untreated control. The ability to create robust articular cartilage from passaged costal

  16. Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid.

    Directory of Open Access Journals (Sweden)

    Edward D Bonnevie

    Full Text Available When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

  17. Articular Cartilage Gene Expression after Coxofemoral Joint Luxation in the Dog

    OpenAIRE

    Korakot Nganvongpanit; Waranee Pradit; Siriwadee Chomdej

    2013-01-01

    This study examined the relationship between days of hip luxation and the expression of various mRNA. Twenty-six articular cartilages were used in the experiment: 3 samples were from normal dogs and 23 samples were collected from the femoral heads of hips that had been luxated for different lengths of time. Ten mRNA, including nonapoptotic genes (AGG, COL2A1, MMP-3, HAS-1, HAS-2, and TIMP-1) and apoptotic genes (BAX, BCL-2, CAS-3, and CAS-9), were studied for their expression using real-time ...

  18. Study on nano-structured hydroxyapatite/zirconia stabilized yttria on healing of articular cartilage defect in rabbit

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    Amir Sotoudeh

    2013-05-01

    Full Text Available PURPOSE: Articular Cartilage has limited potential for self-repair and tissue engineering approaches attempt to repair articular cartilage by scaffolds. We hypothesized that the combined hydroxyapatite and zirconia stabilized yttria would enhance the quality of cartilage healing. METHODS: In ten New Zealand white rabbits bilateral full-thickness osteochondral defect, 4 mm in diameter and 3 mm depth, was created on the articular cartilage of the patellar groove of the distal femur. In group I the scaffold was implanted into the right stifle and the same defect was created in the left stifle without any transplant (group II. Specimens were harvested at 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type-II collagen. RESULTS: In group I the defect was filled with a white translucent cartilage tissue In contrast, the defects in the group II remained almost empty. In the group I, the defects were mostly filled with hyaline-like cartilage evidenced but defects in group II were filled with fibrous tissue with surface irregularities. Positive immunohistochemical staining of type-II collagen was observed in group I and it was absent in the control group. CONCLUSION: The hydroxyapatite/yttria stabilized zirconia scaffold would be an effective scaffold for cartilage tissue engineering.

  19. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    Science.gov (United States)

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

  20. Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique

    Directory of Open Access Journals (Sweden)

    Zheng Ming H

    2008-07-01

    Full Text Available Abstract Introduction The collagen structure in the superficial zone of articular cartilage is critical to the tissue's durability. Early osteoarthritis is often characterized with fissures on the articular surface. This is closely related to the disruption of the collagen network. However, the traditional histology can not offer visualization of the collagen structure in articular cartilage because it uses conventional optical microscopy that does not have insufficient imaging resolution to resolve collagen from proteoglycans in hyaline articular cartilage. This study examines the 3D collagen network of articular cartilage scored from 0 to 2 in the scoring system of International Cartilage Repair Society, and aims to develop a 3D histology for assessing early osteoarthritis. Methods Articular cartilage was visually classified into five physiological groups: normal cartilage, aged cartilage, cartilage with artificial and natural surface disruption, and fibrillated. The 3D collagen matrix of the cartilage was acquired using a 3D imaging technique developed previously. Traditional histology was followed to grade the physiological status of the cartilage in the scoring system of International Cartilage Repair Society. Results Normal articular cartilage contains interwoven collagen bundles near the articular surface, approximately within the lamina splendens. However, its collagen fibres in the superficial zone orient predominantly in a direction spatially oblique to the articular surface. With age and disruption of the articular surface, the interwoven collagen bundles are gradually disappeared, and obliquely oriented collagen fibres change to align predominantly in a direction spatially perpendicular to the articular surface. Disruption of the articular surface is well related to the disappearance of the interwoven collagen bundles. Conclusion A 3D histology has been developed to supplement the traditional histology and study the subtle changes in

  1. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    Science.gov (United States)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  2. Intensity-Dependent Effect of Treadmill Running on Knee Articular Cartilage in a Rat Model

    Directory of Open Access Journals (Sweden)

    Guo-Xin Ni

    2013-01-01

    Full Text Available Objective. To understand the changes of femoral cartilage in response to treadmill running with different intensities in the hope of differentiating “moderate” and “strenuous” running in a rat model. Method. A total of 24 male Wistar rats were randomly assigned into groups of sedentary (SED, low-intensity running (LIR, medium-intensity running (MIR, and high-intensity running (HIR. Rats in LIR, MIR, and HIR groups underwent 8 weeks’ treadmill running programs. After sacrificed, femoral condyles were collected to take histomorphometric analysis and immunohistochemistry for collagen II. Results. Gross and histological observation showed osteoarthritic changes in group HIR. In comparison to SED group, there was significant increase in cartilage thickness, number of chondrocytes, and GAG content in groups LIR and MIR. Conversely, decrease in cartilage thickness, chondrocyte number, and GAG content was found in rats of HIR group, without significant difference though. In addition, in comparison to SED group, HIR group exhibited disorganization of collagen fibril and significantly lower content of collagen type II. Conclusion. An intensity-dependent effect was suggested on the articular cartilage. Our results also demonstrated that running with low-to-medium intensity applied in the present study should be regarded as “moderate” running, whereas high-intensity running as “strenuous” running.

  3. HISTOMORPHOMETRIC ANALYSIS OF THE KNEE ARTICULAR CARTILAGE AND SYNOVIUM FOR METADIAPHYSEAL LEG LENGTHENING (EXPERIMENTAL-AND-MORPHOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    T. A. Stupina

    2013-01-01

    Full Text Available The knee articular cartilage and synovial membrane have been studied for metadiaphyseal leg lengthening using the methods of light miscroscopy, computer morpho- and stereometry. The manner of bone integrity breaking, the rate and rhythm of distraction conformed to the lengthening technique most often used in the clinic. The results of the histomorphometric analysis have demonstrated that when osteotomy at the level of metadiaphysis and manual distraction by 1 mm a day for 4 times is performed, synovitis of mild and moderate degree develops through subsynovial layer hypervascularization, as well as reactive-destructive changes in nerve fibers with the tendency to regeneration. The structural-functional changes of reactive and/or destructive-reparative character have been revealed in the articular cartilage, and the manifestation degree of these changes correlates with synovial membrane changes. The intensity of the destructive-reparative processes in the articular cartilage and synovial membrane depends on fixation stability.

  4. In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.

    Science.gov (United States)

    Tong, Wenxue; Geng, Yiyun; Huang, Yan; Shi, Yu; Xiang, Shengnan; Zhang, Ning; Qin, Ling; Shi, Qin; Chen, Qian; Dai, Kerong; Zhang, Xiaoling

    2015-10-01

    Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1β (IL-1β) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy. © 2015 AlphaMed Press.

  5. C2K77 ELISA detects cleavage of type II collagen by cathepsin K in equine articular cartilage.

    Science.gov (United States)

    Noé, B; Poole, A R; Mort, J S; Richard, H; Beauchamp, G; Laverty, S

    2017-12-01

    Develop a species-specific ELISA for a neo-epitope generated by cathepsin K cleavage of equine type II collagen to: (1) measure cartilage type II collagen degradation by cathepsin K in vitro, (2) identify cytokines that upregulate cathepsin K expression and (3) compare cathepsin K with matrix metalloproteinase (MMP) collagenase activity in stimulated cartilage explants and freshly isolated normal and osteoarthritic (OA) articular cartilages. A new ELISA (C2K77) was developed and tested by measuring the activity of exogenous cathepsin K on equine articular cartilage explants. The ELISA was then employed to measure endogenous cathepsin K activity in cultured cartilage explants with or without stimulation by interleukin-1 beta (IL-1β), tumour necrosis-alpha (TNF-α), oncostatin M (OSM) and lipopolysaccharide (LPS). Cathepsin K activity in cartilage explants (control and osteoarthritic-OA) and freshly harvested cartilage (control and OA) was compared to that of MMPs employing C2K77 and C1,2C immunoassays. The addition of Cathepsin K to normal cartilage caused a significant increase (P K77 epitope release. Whereas the content of C1,2C, that reflects MMP collagenase activity, was increased in media by the addition to cartilage explants of TNF-α and OSM (P K77 which also unchanged in OA cartilages compared to normal. The ELISA C2K77 measured the activity of cathepsin K in equine cartilage which was unchanged in OA cartilage. Cytokines that upregulate MMP collagenase activity had no effect on endogenous cathepsin K activity, suggesting a different activation mechanism that requires further study. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Ongoing studies of cell-based therapies for articular cartilage defects in Japan

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    Ogura T

    2014-12-01

    Full Text Available Takahiro Ogura,1 Akihiro Tsuchiya,2 Shuichi Mizuno1 1Department of Orthopedic Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; 2Funabashi Orthopaedic Hospital Sports Medicine Center, Funabashi, Chiba, Japan Abstract: Recently, cell-based therapies have generated great interest in the repair of articular cartilage defects and degeneration. Surgical treatments for these indications have multiple options, including marrow stimulation, osteochondral autograft transplant, and autologous chondrocyte implantation. The autologous chondrocyte implantation technique has been improved using a cell scaffold and other devices. Meanwhile, advanced cell-based therapies, including cultured stem cell treatment, have been studied in clinical trials. Most studies have been designed and authorized by institutional review boards and/or the regulatory agencies of the investigators’ countries. For cellular products in regenerative medicine, regulations of many countries are amenable to expedited approval. This paper aims to provide an update on ongoing and prospective cell-based therapies, focusing on articular cartilage injury at designated institutions authorized by the Japanese Pharmaceutical and Medical Device Agency. Keywords: autologous chondrocyte implantation, mesenchymal stem cell, knee joint

  7. The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage.

    Science.gov (United States)

    Meng, Qingen; An, Shuqiang; Damion, Robin A; Jin, Zhongmin; Wilcox, Ruth; Fisher, John; Jones, Alison

    2017-01-01

    The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three-layered orientation was used for Model 2. Models 3-5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis.

    Science.gov (United States)

    Klocke, Rainer; Levasseur, Kirsty; Kitas, George D; Smith, Jacqueline P; Hirsch, George

    2018-02-02

    Intra-articular corticosteroid injections (IACI) are commonly used interventions for pain relief in patients with knee osteoarthritis (OA). Biomarkers may be helpful in further elucidating how IACI exert their effect. The aim of this study is to look at the response of biomarkers of cartilage and bone metabolism after IACI in knee OA. Eighty subjects with symptomatic knee OA [45% male, mean age (SD) 64 (11) years] underwent routine knee joint injection with 40 mg triamcinolone acetonide and 4 ml 1% lignocaine. Knee pain (as pain subscale of WOMAC VAS) and biomarkers [C-telopeptides of type-II collagen (uCTX-II), and N-telopeptides of type-I collagen in urine; cartilage oligomeric matrix protein (COMP), hyaluronic acid, N-terminal propeptide of type-IIA collagen, and human cartilage glycoprotein-39 (YKL-40) in serum] were measured at baseline and 3 weeks after IACI. Radiographic severity of disease was evaluated using knee radiographs. Median uCTX-II, a cartilage degradation marker, was lower at 3 weeks post IACI compared with baseline: 306.3 and 349.9 ng/mmol, respectively (p < 0.01), which remained significant after Bonferroni correction. Apart from a weak trend of lower sCOMP post IACI (p = 0.089), other biomarkers showed no change after IACI. Both baseline uCTX-II values and the change in uCTX-II from baseline to 3 weeks post injection correlated with radiographic severity of joint space narrowing, but not osteophyte grade. No association between uCTX-II and pain was observed. This observational study suggests that IACI in knee OA may reduce cartilage degradation in the short term.

  9. Articular Cartilage Lesion Characteristic Reporting Is Highly Variable in Clinical Outcomes Studies of the Knee.

    Science.gov (United States)

    Jones, Kristofer J; Sheppard, William L; Arshi, Armin; Hinckel, Betina B; Sherman, Seth L

    2018-02-01

    Objective The purpose of this study was to investigate the degree of standardized evaluation and reporting of cartilage lesion characteristics in high-impact clinical studies for symptomatic lesions of the knee. We hypothesized that there are significant inconsistencies in reporting these metrics across orthopedic literature. Design A total of 113 clinical studies on articular cartilage restoration of the knee were identified from 6 high-impact orthopedic journals between 2011 and 2016. Full-text review was used to evaluate sources for details on study methodology and reporting on the following variables: primary procedure, location, size, grade, and morphology of cartilage lesions. Results All studies reported on the type of primary cartilage procedure and precise lesion location(s). Approximately 99.1% reported lesion morphology (chondral, osteochondral, mixed). For lesion size, 32.7% of articles did not report how size was measured and 11.5% did not report units. The lesion sizing method was variable, as 27.4% used preoperative magnetic resonance imaging to measure/report lesion size, 31.0% used arthroscopy, and 8.8% used both. The majority of studies (83.2%) used area to report size, and 5.3% used diameter. Formal grading was not reported in 17.7% of studies. Only 54.8% of studies reported depth when sizing osteochondral defects. Conclusions Recent literature on cartilage restoration provides adequate information on surgical technique, lesion location, and morphology. However, there is wide variation and incomplete reporting on lesion size, depth, and grading. Future clinical studies should include these important data in a consistent manner to facilitate comparison among surgical techniques.

  10. Anisotropy of collagen fibre alignment in bovine cartilage: comparison of polarised light microscopy and spatially resolved diffusion-tensor measurements.

    Science.gov (United States)

    de Visser, S K; Bowden, J C; Wentrup-Byrne, E; Rintoul, L; Bostrom, T; Pope, J M; Momot, K I

    2008-06-01

    To compare collagen fibre alignment angles obtained from polarised light microscopy (PLM) and diffusion-tensor imaging (DTI) in bovine articular cartilage. Five samples of bovine articular cartilage from five different animals were studied using magnetic resonance imaging and PLM techniques. T(2)-weighted, diffusion-tensor (DT), and PLM images were acquired for each sample and average depth profiles of the PLM and DTI angles, as well as the banding patterns observed in T(2)-weighted magnetic resonance (MR) images, were compared. Statistical properties of the distributions of the DTI and PLM angles were examined. The samples exhibited a range of alignment morphologies. In the samples with the "conventional" three-zone alignment pattern, a correlation between the PLM and DTI alignment zones and the banding in T(2)-weighted MR images was observed. The shapes of the depth profiles of the PLM and DTI alignment angles were qualitatively similar for each sample. Three samples showed good quantitative correlation between the DT and PLM alignment angles. The correlation between the diffusion and PLM alignment angles was best in the regions of low degree of disorder of fibre alignment. This study provides the first quantitative comparison of DTI of cartilage with the more established PLM techniques. The correlation between alignment angles derived from PLM and DTI data was evident across a wide range of alignment morphologies. The results support the use of DTI for the quantitative measurement of collagen fibre alignment. The microscopic-scale (~10 microm) dispersion of fibre alignment angles appears to be an important factor for understanding the extent of quantitative correlation between PLM and DTI results.

  11. Preparation of Extracellular Matrix Developed Using Porcine Articular Cartilage and In Vitro Feasibility Study of Porcine Articular Cartilage as an Anti-Adhesive Film

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    Ji Hye Baek

    2016-01-01

    Full Text Available In this study, we examined whether porcine articular cartilage (PAC is a suitable and effective anti-adhesive material. PAC, which contained no non-collagenous tissue components, was collected by mechanical manipulation and decellularization of porcine knee cartilage. The PAC film for use as an anti-adhesive barrier was easily shaped into various sizes using homemade silicone molds. The PAC film was cross-linked to study the usefulness of the anti-adhesive barrier shape. The cross-linked PAC (Cx-PAC film showed more stable physical properties over extended periods compared to uncross-linked PAC (UnCx-PAC film. To control the mechanical properties, Cx-PAC film was thermally treated at 45 °C or 65 °C followed by incubation at room temperature. The Cx-PAC films exhibited varying enthalpies, ultimate tensile strength values, and contact angles before and after thermal treatment and after incubation at room temperature. Next, to examine the anti-adhesive properties, human umbilical vein endothelial cells (HUVECs were cultured on Cx-PAC and thermal-treated Cx-PAC films. Scanning electron microscopy, fluorescence, and MTT assays showed that HUVECs were well adhered to the surface of the plate and proliferated, indicating no inhibition of the attachment and proliferation of HUVECs. In contrast, Cx-PAC and thermal-treated Cx-PAC exhibited little and/or no cell attachment and proliferation because of the inhibition effect on HUVECs. In conclusion, we successfully developed a Cx-PAC film with controllable mechanical properties that can be used as an anti-adhesive barrier.

  12. Advances in the Surgical Management of Articular Cartilage Defects: Autologous Chondrocyte Implantation Techniques in the Pipeline.

    Science.gov (United States)

    Stein, Spencer; Strauss, Eric; Bosco, Joseph

    2013-01-01

    The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process. A PubMed search was performed using the phrase "Autologous Chondrocyte Implantation" alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company websites were referenced. Two-Stage Techniques: BioCart II uses a FGF2v1 culture and a fibrinogen, thrombin matrix, whereas Hyalograft-C uses a Hyaff 11 matrix. MACI uses a collagen I/III matrix. Cartipatch consists of an agarose-alginate hydrogel. Neocart uses a high-pressure bioreactor for culturing with a type I collagen matrix. ChondroCelect makes use of a gene expression analysis to predict chondrocyte proliferation and has demonstrated significant clinical improvement, but failed to show superiority to microfracture in a phase III trial. One Step Technique: CAIS is an ACI procedure where harvested cartilage is minced and implanted into a matrix for defect filling. As full thickness defects in articular cartilage continue to pose a challenge to treat, new methods of repair are being researched. Later generation ACI has been developed to address the prevalence of fibrocartilage with microfracture and the complications associated with the periosteal flap of first generation ACI such as periosteal hypertrophy. The procedures and products reviewed here represent advances in tissue engineering, scaffolds and autologous chondrocyte culturing that may hold promise in our quest to alter the natural history of symptomatic chondral disease.

  13. Characterization of an additional articular cartilage vesicle fraction that generates calcium pyrophosphate dihydrate crystals in vitro.

    Science.gov (United States)

    Derfus, B; Steinberg, M; Mandel, N; Buday, M; Daft, L; Ryan, L

    1995-08-01

    We previously identified a unique fraction of porcine articular cartilage vesicles, sedimentable at 8 x 10(6) g/min, which generate calcium pyrophosphate dihydrate crystals (CPPD) in vitro. We sought to identify and characterize other fractions of articular cartilage digest, sedimentable at lower g forces, which may also contain mineralizing vesicles. Electron microscopy and alkaline phosphatase and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) assays were used to analyze each fraction. Radiometric mineralization assays, Fourier transform infrared (FTIR) spectroscopy, and compensated polarized light microscopy were used to analyze crystals formed by these fractions. Vesicles of varying sizes identical to epiphyseal cartilage matrix vesicles were seen in all sedimentable fractions examined, but were the exclusive component of fractions sedimentable at 3 x 10(6) g/min, termed the heavy vesicle fraction (HVF), and at 8 x 10(6) g/min, now termed the light vesicle fraction (LVF). All vesicle containing fractions supported ATP dependent calcium pyrophosphate precipitation. The HVF and LVF precipitated 30 x more calcium than vesicle poor supernatant (p < 0.01) and 1.5-4 x more than cell-free unfractionated digest (p < 0.01). HVF differed from LVF in that it contained 3-4 x higher NTPPPH specific activity (p < 0.05). HVF resembled LVF in that both precipitated crystals consistent with CPPD by FTIR spectroscopy and compensated polarized light microscopy. These data expand our previous estimate of the total number of vesicles available for biologic mineralization and demonstrate heterogeneity of vesicle fractions. They support a key role for vesicles in CPPD crystal formation.

  14. Chondrogenic potential of canine articular cartilage derived cells (cACCs

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    Nowak Urszula

    2016-01-01

    Full Text Available In the present paper, the potential of canine articular cartilage-derived cells (cACCs for chondrogenic differentiation was evaluated. The effectiveness of cACCs’ lineage commitment was analyzed after 14 days of culture in chondorgenic and non-chondrogenic conditions. Formation of proteoglycan-rich extracellular matrix was assessed using histochemical staining – Alcian Blue and Safranin-O, while elemental composition was determined by means of SEM-EDX. Additionally, ultrastructure of cACCs was evaluated using TEM. The expression of genes involved in chondrogenesis was monitored with quantitative Real Time PCR. Results obtained indicate that the potential of cACCs for cartilagous extracellular matrix formation may be maintained only in chondrogenic cultures. The formation of specific chondro-nodules was not observed in a non-chondrogenic culture environment. The analysis of cACCs’ ultrastructure, both in non-chondrogenic and chondrogenic cultures, revealed well-developed rough endoplasmatic reticulum and presence of mitochondria. The cACCs in chondrogenic medium shed an increased number of microvesicles. Furthermore, it was shown that the extracellular matrix of cACCs in chondrogenic cultures is rich in potassium and molybdenum. Additionally, it was determined that gene expression of collagen type II, aggrecan and SOX-9 was significantly increased during chondrogenic differentiation of cACCs. Results obtained indicate that the culture environment may significantly influence the cartilage phenotype of cACCs during long term culture.

  15. Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model

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    Georgi I Kapitanov

    2016-10-01

    Full Text Available Post-traumatic osteoarthritis affects almost 20% of the adult US population. An injurious impact applies a significant amount of physical stress on articular cartilage and can initiate a cascade of biochemical reactions that can lead to the development of osteoarthritis. In our effort to understand the underlying biochemical mechanisms of this debilitating disease, we have constructed a multiscale mathematical model of the process with three components: cellular, chemical, and mechanical. The cellular component describes the different chondrocyte states according to the chemicals these cells release. The chemical component models the change in concentrations of those chemicals. The mechanical component contains a simulation of a blunt impact applied onto a cartilage explant and the resulting strains that initiate the biochemical processes. The scales are modeled through a system of partial-differential equations and solved numerically. The results of the model qualitatively capture the results of laboratory experiments of drop-tower impacts on cartilage explants. The model creates a framework for incorporating explicit mechanics, simulated by finite element analysis, into a theoretical biology framework. The effort is a step toward a complete virtual platform for modeling the development of post-traumatic osteoarthritis, which will be used to inform biomedical researchers on possible non-invasive strategies for mitigating the disease.

  16. Fourier-transform infrared anisotropy in cross and parallel sections of tendon and articular cartilage

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    Bidthanapally Aruna

    2008-10-01

    Full Text Available Abstract Background Fourier Transform Infrared Imaging (FTIRI is used to investigate the amide anisotropies at different surfaces of a three-dimensional cartilage or tendon block. With the change in the polarization state of the incident infrared light, the resulting anisotropic behavior of the tissue structure is described here. Methods Thin sections (6 μm thick were obtained from three different surfaces of the canine tissue blocks and imaged at 6.25 μm pixel resolution. For each section, infrared imaging experiments were repeated thirteen times with the identical parameters except a 15° increment of the analyzer's angle in the 0° – 180° angular space. The anisotropies of amide I and amide II components were studied in order to probe the orientation of the collagen fibrils at different tissue surfaces. Results For tendon, the anisotropy of amide I and amide II components in parallel sections is comparable to that of regular sections; and tendon's cross sections show distinct, but weak anisotropic behavior for both the amide components. For articular cartilage, parallel sections in the superficial zone have the expected infrared anisotropy that is consistent with that of regular sections. The parallel sections in the radial zone, however, have a nearly isotropic amide II absorption and a distinct amide I anisotropy. Conclusion From the inconsistency in amide anisotropy between superficial to radial zone in parallel section results, a schematic model is used to explain the origins of these amide anisotropies in cartilage and tendon.

  17. Pain perception in knees with circumscribed cartilage lesions is associated with intra-articular IGF-1 expression

    DEFF Research Database (Denmark)

    Schmal, Hagen; Niemeyer, Philipp; Südkamp, Norbert P

    2011-01-01

    BACKGROUND: Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans. PURPOSE: This study aimed to reveal...... relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation. STUDY DESIGN: Descriptive laboratory study. METHODS: In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19......, IGF-1, and bFGF was significantly diminished compared to nonsmokers (P smoking negatively influenced...

  18. Laser radiation effect on chondrocytes and intercellular matrix of costal and articular cartilage impregnated with magnetite nanoparticles.

    Science.gov (United States)

    Soshnikova, Yulia M; Shekhter, Anatoly B; Baum, Olga I; Shcherbakov, Evgeniy M; Omelchenko, Alexander I; Lunin, Valeriy V; Sobol, Emil N

    2015-03-01

    Magnetic nanoparticles with the ability to absorb laser radiation are the perspective agents for the early diagnostics and laser therapy of degenerative cartilage. The effect of starch stabilized magnetite nanoparticles (SSNPs) on the cartilage structure components has never been studied before. The aim of the work is to establish the Erbium:glass laser effect on costal and articular cartilage impregnated with SSNPs. Porcine articular and costal cartilage disks (2.0 mm in diameter and 1.5-2 mm in thickness) were impregnated with SSNPs and irradiated using a 1.56 μm laser in therapeutic laser setting. The one sample group underwent the second irradiation after the SSNPs impregnation. The samples were analyzed by the means of histology, histochemistry and transmission electron microscopy (TEM) to reveal the alterations of cells, glycosaminoglycans and collagen network. The irradiated cartilage demonstrates the higher content of cell alterations than the intact one due to the heat and mechanical affection in the course of laser irradiation. However the alterations are localized at the areas near the irradiated surfaces and not dramatic. The impregnation of SSNPs does not cause any additional cell alterations. For both costal and articular cartilage the matrix alterations of irradiated samples are not critical: there is the slight decrease in acid proteoglycan content at the irradiated areas while the collagen network is not altered. Distribution and localization of impregnated SSNPs is described: agglomerates of 150-230 nm are observed located at the borders between matrix and cell lacunas of articular cartilage; SSNPs of 15-45 nm are found in the collagen network of costal cartilage. It was shown that SSNPs do not appreciably affect the structural components of both articular and costal cartilage and can be safely used for the laser diagnostics and therapy. The area of structural alterations is diffuse and local as the result of the mechanical and heat

  19. The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis

    DEFF Research Database (Denmark)

    Harbo, M; Delaisse, J M; Kjaersgaard-Andersen, P

    2013-01-01

    Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human...

  20. Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

    DEFF Research Database (Denmark)

    Langenmair, E. R.; Kubosch, E. J.; Salzmann, G. M.

    2015-01-01

    Objective. Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition o...

  1. Efficacy of diagnostic magnetic resonance imaging for articular cartilage lesions of the glenohumeral joint in patients with instability

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, Meredith L.; Collins, Mark S.; Wenger, Doris E. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Morgan, Joseph A.; Dahm, Diane L. [Mayo Clinic, Department of Orthopaedic Surgery, Rochester, MN (United States)

    2010-12-15

    The purpose of this study was primarily to assess the diagnostic performance of magnetic resonance imaging (MRI) in detecting articular cartilage injuries in patients with glenohumeral instability. A secondary purpose was to assess the diagnostic performance of MRI for detection of Hill-Sachs and Bankart lesions. A cohort of 87 consecutive patients who underwent diagnostic MRI and shoulder arthroscopy for instability from 1997 to 2006 were identified. Fifty-five patients (63.2%) underwent MRI with intra-articular contrast medium and 32 patients (36.8%) underwent MRI without contrast medium. MR images were reviewed by two radiologists and interpreted by consensus for the presence of articular cartilage lesions (including Hill-Sachs and Bankart lesions), which were then confirmed by reviewing the operative report and images recorded at arthroscopy. Mean patient age was 27.0 {+-} 10.2 years with a mean clinical and radiographic follow-up of 29 (range 3-72) months. Cartilage injuries were detected arthroscopically in 55 patients (63%). Bankart and Hill-Sachs lesions were identified arthroscopically in 66 patients (75.9%) and 55 patients (63.2%) respectively. The overall sensitivity and specificity for detection of glenohumeral articular cartilage lesions by MRI were 87.2% and 80.6% respectively. The sensitivity and specificity of MRI in detecting Bankart lesions was 98.4% (95% CI 91.9, 99.7) and 95.2% (95% CI 77.3, 99.2) respectively. The sensitivity and specificity of MRI in detecting Hill-Sachs lesions was 96.3% (95% CI 87.6, 98.9%) and 90.6% (95% CI 75.7, 96.9) respectively. No statistically significant difference was found between MRI examinations with and without intra-articular gadolinium (p = 0.89). Magnetic resonance imaging demonstrates high sensitivity and specificity for the diagnosis of articular cartilage injuries in patients with glenohumeral instability. MRI with or without intra-articular contrast medium in this study were equally reliable as a non

  2. Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials.

    Science.gov (United States)

    Becher, Christoph; Ricklefs, Marcel; Willbold, Elmar; Hurschler, Christof; Abedian, Reza

    2016-01-01

    To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and histological evaluation tools and sulfated glycosaminoglycan (sGAG) content. Streaming potentials are induced in cartilage in response to loading when mobile positive ions in the interstitial fluid temporarily move away from negatively charged proteoglycans. Streaming potential integrals (SPIs) were measured with an indentation probe on femoral condyles of 10 human knee specimens according to a standardized location scheme. Interobserver reliability was measured using an interclass correlation coefficient (ICC). The learning curves of 3 observers were evaluated by regression analysis. At each SPI measurement location the degradation level of the tissue was determined by means of the International Cartilage Repair Society (ICRS) score, Mankin score, and sGAG content. The computed ICC was 0.77 (0.70-0.83) indicating good to excellent linear agreement of SPI values among the 3 users. A significant positive linear correlation of the learning index values was observed for 2 of the 3 users. Statistically significant negative correlations between SPI and both ICRS and Mankin scores were observed (r = 0.502, P < 0.001, and r = 0.255, P = 0.02, respectively). No correlation was observed between SPI and sGAG content (r = 0.004, P = 0.973). SPI values may be used as a quantitative means of cartilage evaluation with sufficient reliability among users. Due to the significant learning curve, adequate training should be absolved before routine use of the technique.

  3. Quantification and age-related distribution of articular cartilage degeneration in the equine fetlock joint.

    Science.gov (United States)

    Brommer, H; van Weeren, P R; Brama, P A J; Barneveld, A

    2003-11-01

    The equine fetlock joint has the largest number of traumatic and degenerative lesions of all joints of the appendicular skeleton. To gain insight into the distribution of cartilage degeneration across the articular surface in relation to age in order better to understand the dynamic nature and progression of osteoarthritis (OA). That there would be a specific age-related distribution pattern of cartilage degeneration in the equine metacarpophalangeal joint. The proximal articular cartilage surfaces of the first phalanges (P1) of 73 slaughter horses (age range 0.4-23 years) with different stages of osteoarthritis were scored semiquantitatively on a 0 to 5 scale and also assessed quantitatively using the cartilage degeneration index (CDI(P1)), which ranges from 0 to 100%. Furthermore, CDI values were determined for special areas of interest; medial dorsal surface (CDI(mds)), lateral dorsal surface (CDI(lds)), medial central fovea (CDI(mcf)) and lateral central fovea (CDI(lcf)). Correlations were calculated for CDI(P1) values and CDI values at the specific areas of interest with macroscopic scores and with age. There was a high correlation between the semiquantitative macroscopic score and the quantitative CDI(P1) values (r = 0.92; P < 0.001). A macroscopic score of 0 (i.e. no obvious cartilage degeneration) corresponded with a CDI(P1) mean +/- s.e. value of 25 +/- 2.8% and a macroscopic score of 5 (i.e. severe cartilage degeneration in localised areas) with a mean +/- s.e. value of 38.1 +/- 7.9%. There was a moderate but highly significant correlation between the CDI(P1) value and the age of the horses (r = 0.41; P < 0.001). Highest CDI values were calculated for the medial dorsal surface (from 10.6 +/- 2.8% at macroscopic Grade 0 to 63.1 +/- 8.4% at Grade 5). At the lateral dorsal surface, these values were 5.9 +/- 1.4% and 47.2 +/- 10.4%, respectively. The CDI(mcf) and CDI(lcf) were significantly lower (P < 0.05) than the CDI(mds) and CDI(lds) at all grades. The

  4. Integrity of articular cartilage on T2 mapping associated with meniscal signal change

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    Kai, Brian [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada); Mann, Sumeer A. [Department of Radiology, University of Alberta, Walter Mackenzie Health Sciences Center, Edmonton, AB, T6G 2B7 (Canada); King, Chris [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada); Forster, Bruce B., E-mail: bruce.forster@vch.ca [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada)

    2011-09-15

    Objective: The purpose of this study was to investigate the relationship between T2 relaxation values (T2 RVs) within the superficial zone of articular cartilage and different types of meniscal degeneration/tear. Materials and methods: A review of 310 consecutive knee MRIs which included an 8 echo T2 relaxation sequence, in patients referred for standard clinical indications, was performed independently and in blinded fashion by 2 observers. The posterior horns of the medial and lateral menisci were each evaluated and divided into 4 subgroups: Normal (control), Grade I/II meniscal signal, Grade III meniscal signal-simple tear (Grade III-S), and Grade III meniscal signal-complex tear (Grade III-C). After exclusion criteria were applied, the medial meniscal group consisted of 65 controls and 133 patients, while the lateral meniscal group consisted of 143 controls and 55 patients. T2 RVs were measured by an observer blinded to the clinical history and MRI grading. Measurements were obtained over the superficial zone of femoral and tibial articular cartilage adjacent to the center of the posterior horn of each meniscus to ensure consistency between measurements. Analysis of covariance adjusting for age and gender was used to compare T2 RVs between patients and controls. Results: T2 RVs were significantly increased in patients with Grade III-C meniscal tears compared to controls over the medial tibial plateau (MTP; p = 0.0001) and lateral tibial plateau (LTP; p = 0.0008). T2 RVs were not increased in patients with Grade III-C meniscal tears over the medial femoral condyle (MFC; p = 0.11) or lateral femoral condyle (LFC; p = 0.99). Grade I/II meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.15), LFC (p = 0.69), MTP (p = 0.42), or LTP (p = 0.50). Grade III-S meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.54), LFC (p = 0.43), MTP (p = 0.30), or LTP (p = 0.38). Conclusion: Grade III-C meniscal tears are associated with

  5. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    2017-01-01

    Full Text Available Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI. The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  6. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

  7. Preparation and Characterization of Poly(vinyl alcohol-chondroitin Sulphate Hydrogel as Scaffolds for Articular Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Shivani Nanda

    2013-01-01

    Full Text Available The aim of the study was to develop PVA-CS hydrogel scaffolds using glutaraldehyde as a cross-linking agent by chemical cross-linking method in order to obtain biomimetic scaffolds for articular cartilage regeneration. The introduction of PVA enhances the mechanical and bioadhesive properties to the native tissue while chondroitin sulphate enhances the glycosaminoglycan content of extracellular matrix. The role of hydrogel as cartilage regeneration scaffold was evaluated by swelling study, porosity, rheological behaviour, in vitro degradation, and quantification of released chondroitin sulphate. In vivo results showed that cross-linked hydrogels repaired defects with no sign of inflammation as it was well anchored to tissue in the formation of new articular surface. It may be concluded that the addition of chondroitin sulphate to the PVA polymer develops a novel composite with significant applications in cartilage tissue engineering.

  8. Protective effects of the pericellular matrix of chondrocyte on articular cartilage against the development of osteoarthritis.

    Science.gov (United States)

    Liu, Chenlu; Wang, Beiyu; Xiao, Li; Li, Yefu; Xu, Lin; Zhao, Zhihe; Zhang, Lin

    2018-01-23

    Understanding the pathogenesis of osteoarthritis (OA) provides invaluable information in the search of therapeutic targets for the development of disease-modifying OA drugs. Emerging results from investigations demonstrate that the pericellular matrix of chondrocytes plays important roles in protecting articular cartilages from being degraded. Thus, maintaining the structural integrity of the pericellular matrix may be an effective approach to prevent the development of osteoarthritic joints. In this review article, we discuss the consequences of lacking one or more components of the pericellular matrix, and biological effects of the destruction of the pericellular matrix in the development of OA. We believe that more attention should be directed towards the pericellular matrix for the identification of novel biomarkers and therapeutic targets for the prevention and treatment of OA.

  9. Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications.

    Science.gov (United States)

    Yan, Le-Ping; Wang, Ying-Jun; Ren, Li; Wu, Gang; Caridade, Sofia G; Fan, Jia-Bing; Wang, Ling-Yun; Ji, Pei-Hong; Oliveira, Joaquim M; Oliveira, João T; Mano, João F; Reis, Rui L

    2010-11-01

    In this study, genipin-cross-linked collagen/chitosan biodegradable porous scaffolds were prepared for articular cartilage regeneration. The influence of chitosan amount and genipin concentration on the scaffolds physicochemical properties was evaluated. The morphologies of the scaffolds were characterized by scanning electron microscope (SEM) and cross-linking degree was investigated by ninhydrin assay. Additionally, the mechanical properties of the scaffolds were assessed under dynamic compression. To study the swelling ratio and the biostability of the collagen/chitosan scaffold, in vitro tests were also carried out by immersion of the scaffolds in PBS solution or digestion in collagenase, respectively. The results showed that the morphologies of the scaffolds underwent a fiber-like to a sheet-like structural transition by increasing chitosan amount. Genipin cross-linking remarkably changed the morphologies and pore sizes of the scaffolds when chitosan amount was less than 25%. Either by increasing the chitosan ratio or performing cross-linking treatment, the swelling ratio of the scaffolds can be tailored. The ninhydrin assay demonstrated that the addition of chitosan could obviously increase the cross-linking efficiency. The degradation studies indicated that genipin cross-linking can effectively enhance the biostability of the scaffolds. The biocompatibility of the scaffolds was evaluated by culturing rabbit chondrocytes in vitro. This study demonstrated that a good viability of the chondrocytes seeded on the scaffold was achieved. The SEM analysis has revealed that the chondrocytes adhered well to the surface of the scaffolds and contacted each other. These results suggest that the genipin-cross-linked collagen/chitosan matrix may be a promising formulation for articular cartilage scaffolding.

  10. Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 in ovariectomized rats.

    Science.gov (United States)

    Li, S; Niu, G; Wu, Y; Du, G; Huang, C; Yin, X; Liu, Z; Song, C; Leng, H

    2016-02-01

    To explore the effect of vitamin D on turnover of articular cartilage with ovariectomy (OVX) induced OA, and to investigate transforming growth factor-β1 (TGF-β1) as a possible underlying mechanism mediated by 1α,25(OH)2D3. Sixty-six rats were randomly allocated into seven groups: sham plus control diet (SHAM+CTL), OVX+CTL diet, sham plus vitamin D-deficient (VDD) diet, OVX+VDD diet, and three groups of ovariectomized rats treated with different doses of 1α,25(OH)2D3. The cartilage erosion and the levels of serum 17β-estradiol, 1α,25(OH)2D3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-β1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-β1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-α), 1α,25(OH)2D3, and TGF-β receptor inhibitor (SB505124) in vitro. Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1α,25(OH)2D3 supplementation, and exacerbated by VDD. The expressions of TGF-β1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1α,25(OH)2D3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1α,25(OH)2D3 supplementation. In vitro experiments showed that 1α,25(OH)2D3 increased the TGF-β1 expression of TNF-α stimulated chondrocytes in a dose-dependent manner. 1α,25(OH)2D3 significantly counteracted the increased CTX-II release due to TNF-α stimulation, and this effect was significantly suppressed by SB505124. VDD aggravated cartilage erosion, and 1α,25(OH)2D3 supplementation showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage

    Directory of Open Access Journals (Sweden)

    Gomez-Reino Juan J

    2008-01-01

    Full Text Available Abstract Background Assessment of gene expression is an important component of osteoarthritis (OA research, greatly improved by the development of quantitative real-time PCR (qPCR. This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Results Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Conclusion Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR.

  12. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

    Directory of Open Access Journals (Sweden)

    Kurokawa Takayuki

    2011-09-01

    Full Text Available Abstract Background We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid and poly-(N, N'-Dimetyl acrylamide, at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage. Methods We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations. Results The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes. Conclusions The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

  13. Multicomponent T2 analysis of articular cartilage with synovial fluid partial volume correction.

    Science.gov (United States)

    Liu, Fang; Chaudhary, Rajeev; Block, Walter F; Samsonov, Alexey; Kijowski, Richard

    2016-05-01

    To investigate the use of a three-pool model to account for the confounding effects of synovial fluid on multicomponent T2 analysis of articular cartilage using Multicomponent Driven Equilibrium Single Shot Observation of T1 and T2 (mcDESPOT). mcDESPOT was performed on the knee of eight asymptomatic volunteers and eight patients with osteoarthritis at 3.0T with multicomponent T2 maps created using the two-pool model and a three-pool model containing a nonexchanging synovial fluid water pool. The fraction of the fast-relaxing water component (FF ) and the T2 relaxation times for the fast-relaxing (T2F ) and slow-relaxing (T2S ) water components were measured in the superficial and deep layers of patellar cartilage using the two-pool and three-pool models in asymptomatic volunteers and patients with osteoarthritis and were compared using Wilcoxon signed rank tests. Within the superficial layer of patellar cartilage, FF was 22.5% and 25.6% for asymptomatic volunteers and 21.3% and 22.8% for patients with osteoarthritis when using the two-pool and three-pool models, respectively, while T2S was 73.9 msec and 62.0 msec for asymptomatic volunteers and 72.0 msec and 63.1 msec for patients with osteoarthritis when using the two-pool and three-pool models, respectively. For both asymptomatic volunteers and patients with osteoarthritis, the two-pool model provided significantly (P multicomponent T2 measurements that can be corrected using an mcDESPOT three-pool model containing a nonexchanging synovial fluid water pool. © 2015 Wiley Periodicals, Inc.

  14. [Changes in the knee joint synovial membrane and articular cartilage during shin lengthening by autodistractor at increased daily rate].

    Science.gov (United States)

    Stupina, T A; Shchudlo, M M; Shchudlo, N A

    2013-01-01

    Light microscopy and computerized morpho- and stereometry were used to examine the changes in the knee joint articular cartilage and synovial membrane studied during experimental canine shin lengthening by 15% of initial length by autodistraction at increased rate - 3 mm per day with switching on the automatic device 120 times. By the end of distraction period (10 days) the destructive changes in articular cartilage were more marked in the superficial and deep zones, synovitis of moderate and mild degree was observed accompanied by the destructive changes in the blood vessels and nerves of the subsynovial layer. Regeneration of articular cartilage was incomplete, and regressive neurovascular changes persisted in synovial membrane 30 days after the device removal. Comparison of these results with the previous data obtained using the distraction rate of 3 mm applied 180 times, leads to the conclusion, significant for functional prognosis, of the worsening the parameters of structural cartilage recovery in case of distraction pitch increase from 0.017 mm to 0.025 mm.

  15. MR evaluation of the articular cartilage of the femoral head during traction. Correlation with resected femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, K. [Osaka Seamens Insurance Hospital (Japan). Dept. of Radiology; Tanaka, H.; Narumi, Y.; Nakamura, H. [Osaka Univ. Medical School (Japan). Dept. of Radiology; Nishii, T.; Masuhara, K. [Osaka Univ. Medical School (Japan). Dept. of Orthopedic Surgery

    1999-01-01

    Objective: The purpose was to evaluate the articular cartilage of the hip joint with MR during traction and compare the findings with the resected specimen or arthroscopic findings. Material and Methods: Eight healthy volunteers, 5 patients with osteonecrosis, 5 with acetabular dysplasia, and 5 with advanced osteoarthrosis underwent MR imaging to evaluate the articular cartilage of the hip joint. Coronal fat-suppressed 3D spoiled gradient-echo (SPGR) images were obtained during traction. Identical imaging was performed of all the resected femoral heads of the osteonecrosis and advanced osteoarthrosis patients, and was correlated with the macroscopic pathological findings. Results: The traction was effective and the femoral articular cartilage was clearly identified in all 8 control subjects, and in all cases of osteonecrosis and acetabular dysplasia. In 4 cases of osteonecrosis, chondral fracture was identified in the boundary between the necrosis and the normal area. In all cases of advanced osteoarthrosis, cartilage was identified only at the medial side. The MR images of osteonecrosis and advanced osteoarthrosis corresponded well with the MR images of the resected femoral heads and the macroscopic findings. (orig.)

  16. [Preliminary study of primarily cultured C57 articular cartilage transfected with plasmid IDO-EGFP by lipofectamine].

    Science.gov (United States)

    Duan, Xiao-Hong; He, Xian-Hui; Cui, Peng-Cheng; Wang, Xiao-Yan; Wu, Ming-Ming; Shi, Jian-Bo; Xu, Geng; Jiang, Xun

    2007-12-01

    To determine the transfection efficiency and transient expression of pIDO-EGFP gene in primarily cultured C57 articular cartilage of mice, and to establish a transfection method of the primarily cultured articular cartilage in mice. Plasmid IDO-EGFP was amplified in Escherichia coli. The primarily cultured mouse chondrocytes which were initially obtained from articular cartilage were cultured in vitro and transfected with pIDO-EGFP by lipofectamine2000 reagent under optimized condition. Transfection process and transient expression were evaluated by fluorescent microscopy and laser scanning confocal microscopy (LSCM), and transfection efficiency was determined by flow cytometry. There was obvious expression of EGFP at 24 h after transfection. The transfection efficiency of pIDO-EGFP into primarily cultured mouse chondrocytes reached 36.43% at 48 hours and the transfection did not affect the process of cell adherence. IDO gene has been successfully transfected into primarily cultured chondrocytes by means of lipofectamine2000 reagent and the chondrocytes can survive in vitro. Satisfactory efficiency of transient transfection can be reached under optimized condition, which will provide a basis for gene introduction and modification of tissue engineered cartilage.

  17. Proteoglycan concentrations in healthy and diseased articular cartilage by Fourier transform infrared imaging and principal component regression

    Science.gov (United States)

    Yin, Jianhua; Xia, Yang

    2014-12-01

    Fourier transform infrared imaging (FTIRI) combining with principal component regression (PCR) analysis were used to determine the reduction of proteoglycan (PG) in articular cartilage after the transection of the anterior cruciate ligament (ACL). A number of canine knee cartilage sections were harvested from the meniscus-covered and meniscus-uncovered medial tibial locations from the control joints, the ACL joints at three time points after the surgery, and their contralateral joints. The PG loss in the ACL cartilage was related positively to the durations after the surgery. The PG loss in the contralateral knees was less than that of the ACL knees. The PG loss in the meniscus-covered cartilage was less than that of the meniscus-uncovered tissue in both ACL and contralateral knees. The quantitative mapping of PG loss could monitor the disease progression and repair processes in arthritis.

  18. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    Directory of Open Access Journals (Sweden)

    Barbara D Boyan

    Full Text Available Osteoarthritis (OA in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OHD3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH2D3] accumulates in articular cartilage following injection of [3H]-25(OHD3. Previously, we showed that 24R,25(OH2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH2D3 or 1α,25(OH2D3. 24R,25(OH2D3 but not 1α,25(OH2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH2D3 or vehicle (t = 0, 7, 14, 21 days. Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.

  19. Comparison of MR-arthrography and MDCT-arthrography for detection of labral and articular cartilage hip pathology

    Energy Technology Data Exchange (ETDEWEB)

    Perdikakis, Evangelos; Karantanas, Apostolos [University Hospital, University of Crete, Department of Radiology, Heraklion (Greece); Karachalios, Theofilos [University of Thessaly, Department of Orthopaedic Surgery, Larissa (Greece); Katonis, Pavlos [University of Crete, Department of Orthopaedics, Heraklion (Greece)

    2011-11-15

    To compare the diagnostic ability of MR arthrography (MRa) and MDCT arthrography (CTa) in depicting surgically proven hip labral tears and articular cartilage degradation. Labral pathology and articular cartilage were prospectively evaluated with MRa and CTa in 14 hips of 10 patients. The findings were evaluated by two independent observers (a musculoskeletal fellow and one senior musculoskeletal radiologist). Sensitivity, specificity, accuracy, and positive predictive value were determined using arthroscopic and open surgery findings as the standard of reference. Interobserver agreement was recorded. All images were assessed for the presence of a labral tear (according to Czerny classification) and for cartilage erosion using a 3 point scale for both methods: 1 = complete visualization-sharp edges, 2 = blurred edges fissuring-partial defects, 3 = exposed bone. The same classification was applied surgically. Disagreement between the senior observer and the fellow observer was recorded in three cases of labral tearing with MRa and six with CTa. Disagreement was also found in four cases of cartilage erosion with both MRa and CTa. The percent sensitivity, specificity, accuracy, and positive predictive value for correctly assessing the labral tear were as follows for MRa/CTa, respectively: 100/15, 50/13, 90/14, and 90/13 (P < 0.05). The same values for cartilage assessment were 63/66, 33/40, 50/57 and 55/66 (P > 0.05). Interobserver reproducibility with MRa is very good for labral tearing assessment. MRa is better for assessing labral tears. CTa shows better, but not statistically significant, demonstration of the articular cartilage. (orig.)

  20. Three-Point Dixon Chemical-Shift Imaging for Evaluating Articular Cartilage Defects in the Knee Joint on a Low-Field-Strength Open Magnet

    National Research Council Canada - National Science Library

    Bredella, M. A; Losasso, C; Moelleken, S. C; Huegli, R. W; Genant, H. K; Tirman, P. F. J

    2001-01-01

    .... OBJECTIVE. The purpose of our study was to assess the value of a modified three-point Dixon MR technique for evaluating articular cartilage defects in the knee joint on a low-field-strength open magnet...

  1. Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T--comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model

    National Research Council Canada - National Science Library

    Goebel, L; Orth, P; Müller, A; Zurakowski, D; Bücker, A; Cucchiarini, M; Pape, D; Madry, H

    2012-01-01

    To develop a new macroscopic scoring system which allows for an overall judgment of experimental articular cartilage repair and compare it with four existing scoring systems and high-field magnetic resonance imaging (MRI...

  2. A novel computational modelling to describe the anisotropic, remodelling and reorientation behaviour of collagen fibrres in articular cartilage

    CERN Document Server

    Cortez, S; Alves, J L

    2016-01-01

    In articular cartilage the orientation of collagen fibres is not uniform, varying mostly with the depth on the tissue. Besides, the biomechanical response of each layer of the articular cartilage differs from the neighbouring ones, evolving through thickness as a function of the distribution, density and orientation of the collagen fibres. Based on a finite element implementation, a new continuum formulation is proposed to describe the remodelling and reorientation of the collagen fibres under arbitrary mechanical loads: the cartilaginous tissue is modelled based on a hyperelastic formulation, being the ground isotropic matrix described by a neo-Hookean law and the fibrillar anisotropic part modelled by a new anisotropic formulation introduced for the first time in the present work, in which both reorientation and remodelling are taken into account. To characterize the orientation of fibres, a structure tensor is defined to represent the expected distribution and orientation of fibres around a reference direc...

  3. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Science.gov (United States)

    Fernandes, Amilton M; Herlofsen, Sarah R; Karlsen, Tommy A; Küchler, Axel M; Fløisand, Yngvar; Brinchmann, Jan E

    2013-01-01

    Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  4. Evaluation of the Quality, Accuracy, and Readability of Online Patient Resources for the Management of Articular Cartilage Defects.

    Science.gov (United States)

    Wang, Dean; Jayakar, Rohit G; Leong, Natalie L; Leathers, Michael P; Williams, Riley J; Jones, Kristofer J

    2017-04-01

    Objective Patients commonly use the Internet to obtain their health-related information. The purpose of this study was to investigate the quality, accuracy, and readability of online patient resources for the management of articular cartilage defects. Design Three search terms ("cartilage defect," "cartilage damage," "cartilage injury") were entered into 3 Internet search engines (Google, Bing, Yahoo). The first 25 websites from each search were collected and reviewed. The quality and accuracy of online information were independently evaluated by 3 reviewers using predetermined scoring criteria. The readability was evaluated using the Flesch-Kincaid (FK) grade score. Results Fifty-three unique websites were evaluated. Quality ratings were significantly higher in websites with a FK score >11 compared to those with a score of ≤11 ( P = 0.021). Only 10 websites (19%) differentiated between focal cartilage defects and diffuse osteoarthritis. Of these, 7 (70%) were elicited using the search term "cartilage defect" ( P = 0.038). The average accuracy of the websites was high (11.7 out of maximum 12), and the average FK grade level (13.4) was several grades higher than the recommended level for readable patient education material (eighth grade level). Conclusions The quality and readability of online patient resources for articular cartilage defects favor those with a higher level of education. Additionally, the majority of these websites do not distinguish between focal chondral defects and diffuse osteoarthritis, which can fail to provide appropriate patient education and guidance for available treatment. Clinicians should help guide patients toward high-quality, accurate, and readable online patient education material.

  5. Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.

    Science.gov (United States)

    Dechant, J E; Baxter, G M; Frisbie, D D; Trotter, G W; McIlwraith, C W

    2003-07-01

    Osteoarthritis is a frequent sequela of joint disease, especially with severe injuries or if attempts at therapy are unsuccessful. Negative and positive effects of corticosteroid treatment of articular cartilage have been demonstrated by in vitro and in vivo studies. To assess the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on interleukin-1alpha (IL-1) conditioned equine cartilage explants. Our hypothesis was that lower dosages of corticosteroids would be less detrimental to cartilage metabolism than higher dosages. TA would be less detrimental to cartilage metabolism than MPA. Treatment groups included articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus 10, 5, 1 and 0.5 mg/ml MPA or 1.2, 0.6, 0.12 and 0.06 mg/ml TA. Explants were labelled with 35SO4 prior to the beginning and end of the experiment to assess glycosaminoglycan (GAG) degradation and synthesis, respectively. Total GAG content in media and explants and total cartilage DNA were also analysed. MPA and TA reduced GAG synthesis compared to control and IL-1 alone. The highest dosage of MPA (10 mg/ml) reduced GAG synthesis less than lower dosages of MPA and all dosages of TA. Compared to IL-1 alone, all dosages of TA and lower dosages of MPA increased GAG degradation. MPA at 10 mg/ml reduced GAG degradation. Both MPA and TA increased media GAG content compared to control and IL-1 explants. Total cartilage GAGs were unchanged with MPA, but reduced with TA, compared with IL-1 alone. Total cartilage DNA was decreased with MPA and increased with TA compared to IL-1 and control explants. MPA and TA did not counteract the negative effects of IL-1 and did not maintain cartilage metabolism at control levels. Lower dosages of MPA and TA were not less detrimental to cartilage metabolism than higher dosages. TA did not appear to be less harmful than MPA on cartilage metabolism. The results of this study differ from the findings of

  6. Pain perception in knees with circumscribed cartilage lesions is associated with intra-articular IGF-1 expression.

    Science.gov (United States)

    Schmal, Hagen; Niemeyer, Philipp; Südkamp, Norbert P; Gerlach, Ulrike; Dovi-Akue, David; Mehlhorn, Alexander T

    2011-09-01

    Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans. This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation. Descriptive laboratory study. In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1β, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay. Pain strength showed a highly significant association with intra-articular IGF-1 levels (ρ = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1β, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage (ρ = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with

  7. T2 mapping of articular cartilage of the glenohumeral joint at 3.0 T in healthy volunteers: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yusuhn [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Choi, Jung-Ah [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Hallym University Dongtan Sacred Heart Hospital, Department of Radiology, Hwaseong, Gyeonggi-do (Korea, Republic of)

    2016-07-15

    The purpose of this study was to assess the T2 values of the glenohumeral joint cartilage in healthy asymptomatic individuals at 3.0 T and to analyze the T2 profile of the humeral cartilage. This prospective study was approved by our institutional review board and written informed consent was obtained. Thirteen subjects (mean age, 28.6 years; age range, 24-33 years) were included and underwent multiecho spin-echo T2-weighted MR imaging and T2 mapping was acquired. Regions of interest were placed on the humeral cartilage and glenoid cartilage on oblique coronal images. T2 profiles of humeral cartilage were measured from the bone-cartilage interface to the articular surface. Intra-observer agreement was analyzed using intraclass correlation coefficient (ICC). All 13 joints showed normal appearance on conventional T2-weighted images. The mean T2 values of humeral and glenoid cartilage were 50.5 ± 12.1 and 49.0 ± 9.9 ms, respectively. Intra-observer agreement was good, as determined by ICC (0.736). Longer T2 values were observed at the articular surface with a tendency to decrease toward the bone-cartilage interface. The mean cartilage T2 value was 69.03 ± 21.2 ms at the articular surface and 46.99 ± 19.6 ms at the bone-cartilage interface. T2 values of the glenohumeral joint cartilage were similar to reported values of cartilage in the knee. The T2 profile of normal humeral cartilage showed a spatial variation with an increase in T2 values from the subchondral bone to the articular surface. (orig.)

  8. Clinically Relevant Subregions of Articular Cartilage of the Hip for Analysis and Reporting Quantitative Magnetic Resonance Imaging

    OpenAIRE

    Rachel K. Surowiec; Lucas, Erin P.; Wilson, Katharine J.; Saroki, Adriana J.; Ho, Charles P.

    2014-01-01

    Objective: Before quantitative imaging techniques can become clinically valuable, the method, and more specifically, the regions of locating and reporting these values should be standardized toward reproducibility comparisons across centers and longitudinal follow-up of individual patients. The purpose of this technical note is to describe a rigorous and reproducible method of locating, analyzing, and reporting quantitative MRI values in hip articular cartilage with an approach that is consis...

  9. Magnetic resonance imaging of the femoral trochlea: evaluation of anatomical landmarks and grading articular cartilage in cadaveric knees

    Energy Technology Data Exchange (ETDEWEB)

    Muhle, Claus [Marienhospital Vechta, Department of Radiology, Vechta (Germany); Veterans Affairs Medical Center, Department of Radiology, San Diego, CA (United States); Mo Ahn, Joong [University of Iowa, Department of Radiology, Iowa, IA (United States); Trudell, Debra; Resnick, Donald [Veterans Affairs Medical Center, Department of Radiology, San Diego, CA (United States)

    2008-06-15

    The purpose of the study was to define magnetic resonance imaging (MRI) findings before and after contrast medium opacification of the knee joint in cadaveric specimens to demonstrate anatomical landmarks of the trochlear surface in relation to the neighboring structures, and to evaluate different MRI sequences in the detection of cartilage defects of the trochlear and patellar surface of the knee. The morphology and relationship of the proximal trochlear surface to the prefemoral fat of the distal femur were investigated by use of different MR sequences before and after intra-articular gadolinium administration into the knee joint in ten cadaveric knees. Anatomic sections were subsequently obtained. In addition, evaluation of the articular surface of the trochlea was performed by two independent observers. The cartilage surfaces were graded using a 2-point system, and results were compared with macroscopic findings. Of 40 cartilage surfaces evaluated, histopathologic findings showed 9 normal surfaces, 20 containing partial-thickness defects, and 11 containing full-thickness defects. Compared with macroscopic data, sensitivity of MR sequences for the two reviewers was between 17 and 90%; specificity, 75 and 100%; positive predictive value, 75 and 100%; negative predictive value, 20 and 100%, depending on patellar or trochlea lesions. Interobserver variability for the presence of disease, which was measured using the kappa statistic, was dependent on the MR sequence used between 0.243 and 0.851. Magnetic resonance imaging sequences can be used to evaluate the cartilage of the trochlear surface with less accuracy when compared with the results of grading the articular cartilage of the patella. (orig.)

  10. Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

    Science.gov (United States)

    Lawrence, Alexandra; Xu, Xin; Bible, Melissa D; Calve, Sarah; Neu, Corey P; Panitch, Alyssa

    2015-12-01

    The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study.

    Directory of Open Access Journals (Sweden)

    Yolande F M Ramos

    Full Text Available Identify gene expression profiles associated with OA processes in articular cartilage and determine pathways changing during the disease process.Genome wide gene expression was determined in paired samples of OA affected and preserved cartilage of the same joint using microarray analysis for 33 patients of the RAAK study. Results were replicated in independent samples by RT-qPCR and immunohistochemistry. Profiles were analyzed with the online analysis tools DAVID and STRING to identify enrichment for specific pathways and protein-protein interactions.Among the 1717 genes that were significantly differently expressed between OA affected and preserved cartilage we found significant enrichment for genes involved in skeletal development (e.g. TNFRSF11B and FRZB. Also several inflammatory genes such as CD55, PTGES and TNFAIP6, previously identified in within-joint analyses as well as in analyses comparing preserved cartilage from OA affected joints versus healthy cartilage were among the top genes. Of note was the high up-regulation of NGF in OA cartilage. RT-qPCR confirmed differential expression for 18 out of 19 genes with expression changes of 2-fold or higher, and immunohistochemistry of selected genes showed a concordant change in protein expression. Most of these changes associated with OA severity (Mankin score but were independent of joint-site or sex.We provide further insights into the ongoing OA pathophysiological processes in cartilage, in particular into differences in macroscopically intact cartilage compared to OA affected cartilage, which seem relatively consistent and independent of sex or joint. We advocate that development of treatment could benefit by focusing on these similarities in gene expression changes and/or pathways.

  12. Multiphasic modeling of charged solute transport across articular cartilage: Application of multi-zone finite-bath model.

    Science.gov (United States)

    Arbabi, Vahid; Pouran, Behdad; Weinans, Harrie; Zadpoor, Amir A

    2016-06-14

    Charged and uncharged solutes penetrate through cartilage to maintain the metabolic function of chondrocytes and to possibly restore or further breakdown the cartilage tissue in different stages of osteoarthritis. In this study the transport of charged solutes across the various zones of cartilage was quantified, taken into account the physicochemical interactions between the solute and the cartilage constituents. A multiphasic finite-bath finite element (FE) model was developed to simulate equine cartilage diffusion experiments that used a negatively charged contrast agent (ioxaglate) in combination with serial micro-computed tomography (micro-CT) to measure the diffusion. By comparing the FE model with the experimental data both the diffusion coefficient of ioxaglate and the fixed charge density (FCD) were obtained. In the multiphasic model, cartilage was divided into multiple (three) zones to help understand how diffusion coefficient and FCD vary across cartilage thickness. The direct effects of charged solute-FCD interaction on diffusion were investigated by comparing the diffusion coefficients derived from the multiphasic and biphasic-solute models. We found a relationship between the FCD obtained by the multiphasic model and ioxaglate partitioning obtained from micro-CT experiments. Using our multi-zone multiphasic model, diffusion coefficient of the superficial zone was up to ten-fold higher than that of the middle zone, while the FCD of the middle zone was up to almost two-fold higher than that of the superficial zone. In conclusion, the developed finite-bath multiphasic model provides us with a non-destructive method by which we could obtain both diffusion coefficient and FCD of different cartilage zones. The outcomes of the current work will also help understand how charge of the bath affects the diffusion of a charged molecule and also predict the diffusion behavior of a charged solute across articular cartilage. Copyright © 2016 Elsevier Ltd. All

  13. Enzymatic digestion of articular cartilage results in viscoelasticity changes that are consistent with polymer dynamics mechanisms

    National Research Council Canada - National Science Library

    June, Ronald K; Fyhrie, David P

    2009-01-01

    .... This study tested whether the predictions of polymer dynamics were consistent with changes in cartilage mechanics caused by enzymatic digestion of specific cartilage extracellular matrix molecules...

  14. Microstructural analysis of collagen and elastin fibres in the kangaroo articular cartilage reveals a structural divergence depending on its local mechanical environment.

    Science.gov (United States)

    He, B; Wu, J P; Chim, S M; Xu, J; Kirk, T B

    2013-01-01

    To assess the microstructure of the collagen and elastin fibres in articular cartilage under different natural mechanical loading conditions and determine the relationship between the microstructure of collagen and its mechanical environment. Articular cartilage specimens were collected from the load bearing regions of the medial femoral condyle and the medial distal humerus of adult kangaroos. The microstructure of collagen and elastin fibres of these specimens was studied using laser scanning confocal microscopy (LSCM) and the orientation and texture features of the collagen were analysed using ImageJ. A zonal arrangement of collagen was found in kangaroo articular cartilage: the collagen fibres aligned parallel to the surface in the superficial zone and ran perpendicular in the deep zone. Compared with the distal humerus, the collagen in the femoral condyle was less isotropic and more clearly oriented, especially in the superficial and deep zones. The collagen in the femoral condyle was highly heterogeneous, less linear and more complex. Elastin fibres were found mainly in the superficial zone of the articular cartilage of both femoral condyle and distal humerus. The present study demonstrates that the collagen structure and texture of kangaroo articular cartilage is joint-dependent. This finding emphasizes the effects of loading on collagen development and suggests that articular cartilage with high biochemical and biomechanical qualities could be achieved by optimizing joint loading, which may benefit cartilage tissue engineering and prevention of joint injury. The existence of elastin fibres in articular cartilage could have important functional implications. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  15. Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness.

    Directory of Open Access Journals (Sweden)

    Anke Jeschke

    Full Text Available Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4. In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its

  16. Comparative study on identification of healthy and osteoarthritic articular cartilages by fourier transform infrared imaging and chemometrics methods

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Mao

    2017-05-01

    Full Text Available Two discriminant methods, partial least squares-discriminant analysis (PLS-DA and Fisher’s discriminant analysis (FDA, were combined with Fourier transform infrared imaging (FTIRI to differentiate healthy and osteoarthritic articular cartilage in a canine model. Osteoarthritic cartilage had been developed for up to two years after the anterior cruciate ligament (ACL transection in one knee. Cartilage specimens were sectioned into 10 μm thickness for FTIRI. A PLS-DA model was developed after spectral pre-processing. All IR spectra extracted from FTIR images were calculated by PLS-DA with the discriminant accuracy of 90%. Prior to FDA, principal component analysis (PCA was performed to decompose the IR spectral matrix into informative principal component matrices. Based on the different discriminant mechanism, the discriminant accuracy (96% of PCA-FDA with high convenience was higher than that of PLS-DA. No healthy cartilage sample was mis-assigned by these two methods. The above mentioned suggested that both integrated technologies of FTIRI-PLS-DA and, especially, FTIRI-PCA-FDA could become a promising tool for the discrimination of healthy and osteoarthritic cartilage specimen as well as the diagnosis of cartilage lesion at microscopic level. The results of the study would be helpful for better understanding the pathology of osteoarthritics.

  17. Synthesis of Tantalum Oxide Nanoparticles for Imaging Articular Cartilage Using X-Ray Computed Tomography: Visualization of Ex vivo/In vivo Murine Tibia and Ex vivo Human Index Finger Cartilage**

    Science.gov (United States)

    Freedman, Jonathan D.; Lusic, Hrvoje; Snyder, Brian D.

    2014-01-01

    Tantalum oxide (Ta2O5) nanoparticles are used as X-ray contrast media for micro computed tomography (μCT) imaging of articular cartilage. The cationic nanoparticles are attracted to the anionic glycosaminoglycans in the cartilage tissue. PMID:24981730

  18. Instruments for reproducible setting of defects in cartilage and harvesting of osteochondral plugs for standardisation of preclinical tests for articular cartilage regeneration.

    Science.gov (United States)

    Schwarz, Markus L; Schneider-Wald, Barbara; Brade, Joachim; Schleich, Dieter; Schütte, Andy; Reisig, Gregor

    2015-07-28

    Standardisation is required in research, so are approval procedures for advanced therapy medical products and other procedures for articular cartilage therapies. The process of creating samples needs to be reproducible. The aim of this study was to design, create and validate instruments (1) to create reproducible and accurate defects and (2) to isolate samples in the shape of osteochondral cylinders in a quick, reliable and sterile manner. Adjustable instruments were created: a crown mill with a resolution of 0.05 mm and a front mill to create defects in articular cartilage and subchondral bone. The instruments were tested on knee joints of pigs from the slaughterhouse; 48 defects were created and evaluated. A punching machine was designed to harvest osteochondral plugs. These were validated in an in vivo animal study. The instruments respect the desired depth of 0.5 and 1.5 mm when creating the defects, depending on whether the person using the instrument is highly experienced (0.451 mm; confidence interval (CI): 0.390 mm; 0.512 mm and 1.403 mm; CI: 1.305 mm; 1.502 mm) or less so (0.369 mm; CI: 0.297 mm; 0.440 mm and 1.241 mm; CI: 1.141 mm; 1.341 mm). Eighty samples were taken from knee joints of Göttingen Minipigs with this punching technique. The time needed for the harvesting of the samples was 7.52 min (±2.18 min), the parallelism of the sides of the cylinders deviated by -0.63° (CI: -1.33°; 0.08°) and the surface of the cartilage deviated from the perpendicularity by 4.86° (CI: 4.154°; 5.573°). In all assessed cases, a sterile procedure was observed. Instruments and procedures for standardised creation and validation of defects in articular cartilage and subchondral bone were designed. Harvesting of samples in the shape of osteochondral cylinders can now be performed in a quick, reliable and sterile manner. The presented instruments and procedures can serve as helpful steps towards standardised operating procedures in the field of

  19. Concentration profiles of collagen and proteoglycan in articular cartilage by Fourier transform infrared imaging and principal component regression

    Science.gov (United States)

    Yin, Jianhua; Xia, Yang; Lu, Mei

    2012-03-01

    Fourier-transform infrared imaging (FT-IRI) technique with the principal component regression (PCR) method was used to quantitatively determine the 2D images and the depth-dependent concentration profiles of two principal macromolecular components (collagen and proteoglycan) in articular cartilage. Ten 6 μm thick sections of canine humeral cartilage were imaged at a pixel size of 6.25 μm in FT-IRI. The infrared spectra extracted from FT-IRI experiments were imported into a PCR program to calculate the quantitative distributions of both collagen and proteoglycan in dry cartilage, which were subsequently converted into the wet-weight based concentration profiles. The proteoglycan profiles by FT-IRI and PCR significantly correlated in linear regression with the proteoglycan profiles by the non-destructive μMRI (the goodness-of-fit 0.96 and the Pearson coefficient 0.98). Based on these concentration relationships, the concentration images of collagen and proteoglycan in both healthy and lesioned articular cartilage were successfully constructed two dimensionally. The simultaneous construction of both collagen and proteoglycan concentration images demonstrates that this combined imaging and chemometrics approach could be used as a sensitive tool to accurately resolve and visualize the concentration distributions of macromolecules in biological tissues.

  20. Rapid multicomponent T2 analysis of the articular cartilage of the human knee joint at 3.0T.

    Science.gov (United States)

    Liu, Fang; Chaudhary, Rajeev; Hurley, Samuel A; Munoz Del Rio, Alejandro; Alexander, Andrew L; Samsonov, Alexey; Block, Walter F; Kijowski, Richard

    2014-05-01

    To determine the feasibility of using multicomponent-driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) for evaluating the human knee joint at 3.0T and to investigate depth-dependent and regional-dependent variations in multicomponent T2 parameters within articular cartilage. mcDESPOT was performed on the knee joint of 10 asymptomatic volunteers at 3.0T. Single-component T2 relaxation time (T2single ), multicomponent T2 relaxation time for water tightly bound to proteoglycan (T2PG ) and bulk water loosely bound to the macromolecular matrix (T2BW ), and fraction of water tightly bound to proteoglycan (FPG ) were measured in eight cartilage subsections and within the superficial and deep layers of patellar cartilage. Statistical analysis was used to investigate depth-dependent and regional-dependent variations in parameters. There was lower (P = 0.001) T2single and T2PG and higher (P Multicomponent T2 parameters of the articular cartilage of the human knee joint can be measured at 3.0T using mcDESPOT and show depth-dependent and regional-dependent variations. Copyright © 2013 Wiley Periodicals, Inc.

  1. Low Levels of Vitamin D have a Deleterious Effect on the Articular Cartilage in a Rat Model.

    Science.gov (United States)

    Pascual-Garrido, Cecilia; Angeline, Michael E; Ma, Richard; Chahla, Jorge; Voigt, Cliff; Deng, Xiang Hua; Nguyen, Joseph; Warren, Russell F; Rodeo, Scott A

    2016-07-01

    Vitamin D appears to play an important role in bone and cartilage metabolism since its receptors are widely found in human articular chondrocytes. Thus, effects of variation of vitamin D may directly impact cartilage and bone biology. The aims of this study are to compare (1) articular cartilage structure and composition and (2) trabecular and cortical bone microstructure in rats with normal versus insufficient vitamin D levels. Twenty-five mature, male Sprague-Dawley rats were allocated to two groups: (1) control arm (vitamin D replete-12 rats) and (2) an experimental arm (vitamin D deficient-13 rats). Vitamin D deficiency was induced using a vitamin D-deficient diet and UV light restriction. Rats were sacrificed after 4 weeks vitamin D deficiency was confirmed. The right knee was harvested for analysis of both the medial (MFC) and lateral femoral condyles (LFC). A region of interest was established on both condyles to correlate subchondral bone architecture and the overlying cartilage. Histological analysis was performed and graded using the modified Mankin score. Subchondral and cortical bony architecture was evaluated with micro-CT. After 4 weeks, the vitamin D-deficient group had statistically significant changes in cartilage structure in both the MFC and LFC [1.55 ± 0.6 vs. 4.23 ± 4.1 (p = 0.035) and 1.55 ± 0.6 vs. 3.53 ± 2.4 (p = 0.009), respectively]. Micro-CT analysis revealed no correlation between subchondral bone values and the overlying cartilage Mankin score (p = 0.460). No significant difference was evident between the subchondral bone of the control and study group. Low levels of vitamin D have a deleterious effect on the cartilage. Given the high prevalence of vitamin D deficiency in the general population, these findings raise important questions about the potential role of vitamin D in articular cartilage health.

  2. Site-specific immunostaining for type X collagen in noncalcified articular cartilage of canine stifle knee joint.

    Science.gov (United States)

    Lammi, P E; Lammi, M J; Hyttinen, M M; Panula, H; Kiviranta, I; Helminen, H J

    2002-12-01

    Type X collagen is a short-chain collagen that is strongly expressed in hypertrophic chondrocytes. In this study, we used an immunohistochemical technique exploiting a prolonged hyaluronidase unmasking of type X collagen epitopes to show that type X collagen is not restricted to calcified cartilage, but is also present in normal canine noncalcified articular cartilage. A 30 degrees valgus angulation procedure of the right tibia was performed in 15 dogs at the age of 3 months, whereas their nonoperated sister dogs served as controls. Samples were collected 7 and 18 months after the surgery and immunostained for type X collagen. The deposition of type X collagen increased during maturation from age 43 weeks to 91 weeks. In the patella, most of the noncalcified cartilage stained for type X collagen, whereas, in the patellar surface of the femur, it was present mainly in the femoral groove close to cartilage surface. In femoral condyles, the staining localized mostly in the superficial cartilage on the lateral and medial sides, but not in the central weight-bearing area. In tibial condyles, type X collagen was often observed close to the cartilage surface in medial parts of the condyles, although staining could also be seen in the deep zone of the cartilage. Staining for type X collagen appeared strongest at sites where the birefringence of polarized light was lowest, suggesting a colocalization of type X collagen with the collagen fibril arcades in the intermediate zone. No significant difference in type X collagen immunostaining was observed in lesion-free articular cartilage between controls and dogs that underwent a 30 degrees valgus osteotomy. In osteoarthritic lesions, however, there was strong immunostaining for both type X collagen and collagenase-induced collagen cleavage products. The presence of type X collagen in the transitional zone of cartilage in the patella, femoropatellar groove, and in tibial cartilage uncovered by menisci suggests that it may

  3. Partial reversal by beta-D-xyloside of salicylate-induced inhibition of glycosaminoglycan synthesis in articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Palmoski, M.J.; Brandt, K.D.

    1982-09-01

    While net /sup 35/S-glycosaminoglycan synthesis in normal canine articular cartilage was suppressed by 10(-3)M sodium salicylate to about 70% of the control value, addition of xyloside (10(-6)M-10(-3)M) to the salicylate-treated cultures led to a concentration-dependent increase in glycosaminoglycan synthesis, which rose to 120-237% of controls. Similar results were obtained when /sup 3/H-glucosamine was used to measure glycosaminoglycan synthesis, confirming that salicylate suppresses and xyloside stimulates net glycosaminoglycan synthesis, and not merely sulfation. Salicylate (10-3)M) did not affect the activity of xylosyl or galactosyl transferase prepared from canine knee cartilage, and net protein synthesis was unaltered by either salicylate or xyloside. The proportion of newly synthesized proteoglycans existing as aggregates when cartilage was cultured with xyloside was similar to that in controls, although the average hydrodynamic size of disaggregated proteoglycans and of sulfated glycosaminoglycans was diminished.

  4. Hyaline Cartilage Tissue Is Formed through the Co-culture of Passaged Human Chondrocytes and Primary Bovine Chondrocytes

    Science.gov (United States)

    Taylor, Drew W.; Ahmed, Nazish; Hayes, Anthony J.; Ferguson, Peter; Gross, Allan E.; Caterson, Bruce

    2012-01-01

    To circumvent the problem of a sufficient number of cells for cartilage engineering, the authors previously developed a two-stage culture system to redifferentiate monolayer culture-expanded dedifferentiated human articular chondrocytes by co-culture with primary bovine chondrocytes (bP0). The aim of this study was to analyze the composition of the cartilage tissue formed in stage 1 and compare it with bP0 grown alone to determine the optimal length of the co-culture stage of the system. Biochemical data show that extracellular matrix accumulation was evident after 2 weeks of co-culture, which was 1 week behind the bP0 control culture. By 3 to 4 weeks, the amounts of accumulated proteoglycans and collagens were comparable. Expression of chondrogenic genes, Sox 9, aggrecan, and collagen type II, was also at similar levels by week 3 of culture. Immunohistochemical staining of both co-culture and control tissues showed accumulation of type II collagen, aggrecan, biglycan, decorin, and chondroitin sulfate in appropriate zonal distributions. These data indicate that co-cultured cells form cartilaginous tissue that starts to resemble that formed by bP0 after 3 weeks, suggesting that the optimal time to terminate the co-culture stage, isolate the now redifferentiated cells, and start stage 2 is just after 3 weeks. PMID:22610463

  5. Fourier transform infrared spectroscopic imaging and multivariate regression for prediction of proteoglycan content of articular cartilage.

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    Lassi Rieppo

    Full Text Available Fourier Transform Infrared (FT-IR spectroscopic imaging has been earlier applied for the spatial estimation of the collagen and the proteoglycan (PG contents of articular cartilage (AC. However, earlier studies have been limited to the use of univariate analysis techniques. Current analysis methods lack the needed specificity for collagen and PGs. The aim of the present study was to evaluate the suitability of partial least squares regression (PLSR and principal component regression (PCR methods for the analysis of the PG content of AC. Multivariate regression models were compared with earlier used univariate methods and tested with a sample material consisting of healthy and enzymatically degraded steer AC. Chondroitinase ABC enzyme was used to increase the variation in PG content levels as compared to intact AC. Digital densitometric measurements of Safranin O-stained sections provided the reference for PG content. The results showed that multivariate regression models predict PG content of AC significantly better than earlier used absorbance spectrum (i.e. the area of carbohydrate region with or without amide I normalization or second derivative spectrum univariate parameters. Increased molecular specificity favours the use of multivariate regression models, but they require more knowledge of chemometric analysis and extended laboratory resources for gathering reference data for establishing the models. When true molecular specificity is required, the multivariate models should be used.

  6. Characterization of a polyvinyl alcohol-hydrogel artificial articular cartilage prepared by injection molding.

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    Kobayashi, Masanori; Oka, Masanori

    2004-01-01

    We have developed a hip hemi-arthroplasty using polyvinyl alcohol-hydrogel (PVA-H) as the treatment for hip joint disorders in which the lesion is limited to the joint surface. In previous studies, we characterized the biocompatibility and the mechanical properties of PVA-H as an arthroplasty material. To fix PVA-H firmly to the bone, we have devised an implant composed of PVA-H and porous titanium fiber mesh (TFM). However, because of poor infiltration of the PVA solution into the pores of the TFM when using the low temperature crystallization method, the strength of the PVA-H-TFM interface was insufficient. Consequently, the infiltration method was improved by adopting high-pressure injection molding. With this improved method, the bonding strength of the interface increased remarkably. However, as this injection molding requires high temperature, various mechanical properties of the PVA-H might change with this treatment in comparison with the previous method. The purpose of this study was to investigate the effect of high temperature treatment on the mechanical properties of PVA-H as artificial articular cartilage, the tensile test and friction test were performed about new PVA-H. The results showed no significant mechanical deterioration of the PVA-H. This certified that the injection-molding method did not induce the change of the mechanical properties of PVA-H and indicated the potential of hemi-arthroplasty using PVA-H by this method in the future.

  7. Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration

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    Parmar, Paresh A.; Chow, Lesley W.; St-Pierre, Jean-Philippe; Horejs, Christine-Maria; Peng, Yong Y.; Werkmeister, Jerome A.; Ramshaw, John A.M.; Stevens, Molly M.

    2015-01-01

    Regenerative medicine strategies for restoring articular cartilage face significant challenges to recreate the complex and dynamic biochemical and biomechanical functions of native tissues. As an approach to recapitulate the complexity of the extracellular matrix, collagen-mimetic proteins offer a modular template to incorporate bioactive and biodegradable moieties into a single construct. We modified a Streptococcal collagen-like 2 protein with hyaluronic acid (HA) or chondroitin sulfate (CS)-binding peptides and then cross-linked with a matrix metalloproteinase 7 (MMP7)-sensitive peptide to form biodegradable hydrogels. Human mesenchymal stem cells (hMSCs) encapsulated in these hydrogels exhibited improved viability and significantly enhanced chondrogenic differentiation compared to controls that were not functionalized with glycosaminoglycan-binding peptides. Hydrogels functionalized with CS-binding peptides also led to significantly higher MMP7 gene expression and activity while the HA-binding peptides significantly increased chondrogenic differentiation of the hMSCs. Our results highlight the potential of this novel biomaterial to modulate cell-mediated processes and create functional tissue engineered constructs for regenerative medicine applications. PMID:25907054

  8. Articular cartilage gene expression after coxofemoral joint luxation in the dog.

    Science.gov (United States)

    Nganvongpanit, Korakot; Pradit, Waranee; Chomdej, Siriwadee

    2013-01-01

    This study examined the relationship between days of hip luxation and the expression of various mRNA. Twenty-six articular cartilages were used in the experiment: 3 samples were from normal dogs and 23 samples were collected from the femoral heads of hips that had been luxated for different lengths of time. Ten mRNA, including nonapoptotic genes (AGG, COL2A1, MMP-3, HAS-1, HAS-2, and TIMP-1) and apoptotic genes (BAX, BCL-2, CAS-3, and CAS-9), were studied for their expression using real-time PCR. We found very high correlation between expression level and luxation days (r (2) > 0.9) in COL2A1, MMP-3, HAS-1, HAS-2, TIMP-1, BAX, and CAS-9, while the others (AGG, BCL-2, and CAS-3) also showed high correlation (r (2) = 7-9). And we found a significant difference (P joint reduction may increase the chances of development of osteoarthritis.

  9. Articular Cartilage Gene Expression after Coxofemoral Joint Luxation in the Dog

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    Korakot Nganvongpanit

    2013-01-01

    Full Text Available This study examined the relationship between days of hip luxation and the expression of various mRNA. Twenty-six articular cartilages were used in the experiment: 3 samples were from normal dogs and 23 samples were collected from the femoral heads of hips that had been luxated for different lengths of time. Ten mRNA, including nonapoptotic genes (AGG, COL2A1, MMP-3, HAS-1, HAS-2, and TIMP-1 and apoptotic genes (BAX, BCL-2, CAS-3, and CAS-9, were studied for their expression using real-time PCR. We found very high correlation between expression level and luxation days (r2>0.9 in COL2A1, MMP-3, HAS-1, HAS-2, TIMP-1, BAX, and CAS-9, while the others (AGG, BCL-2, and CAS-3 also showed high correlation (r2=7–9. And we found a significant difference (P<0.05 in the expression of transcripts depending on the number of luxation days. In conclusion, a delay in joint reduction may increase the chances of development of osteoarthritis.

  10. Clinical platform for understanding the relationship between joint contact mechanics and articular cartilage changes after meniscal surgery.

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    Maher, Suzanne A; Wang, Hongsheng; Koff, Matthew F; Belkin, Nicole; Potter, Hollis G; Rodeo, Scott A

    2017-03-01

    Injury to the meniscus of the knee has been implicated as a significant risk factor for the subsequent development of osteoarthritis, but the mechanisms of joint degeneration are unclear. Our objective was to develop a clinically applicable methodology to evaluate the relationship of joint contact mechanics at the time of surgery to biological changes of articular cartilage as a function of time following surgery. A series of pre-, intra-, and post-operative protocols were developed which utilized electronic sensors for the direct measurement of contact mechanics, and advanced imaging to assess cartilage health. The tests were applied to a pilot cohort of young active patients undergoing meniscus allograft transplantation. Our study demonstrated significant variability across patients in terms of contact area and peak contact stress, both before and after transplantation. Nonetheless, the majority of patients exhibited decreased peak contact stress and increased contact area after graft implantation. MR scans at 3-6 months showed decreased T1ρ values in tibial articular cartilage, suggesting an increase in proteoglycan content or concomitant decrease in water content. Prolongation of T2 values was found primarily within the central, cartilage-cartilage contact region of the tibial plateau suggested disruption of the collagen network. Minimal differences were found in cartilage thickness over the short time frame of this preliminary study. With longer clinical follow-up, our platform of clinical tests can be used to better understand the patient-specific mechanical factors that are related to increased risk of OA after meniscus injury and surgery. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:600-611, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

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    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis

  12. A comparative analysis of 7.0-Tesla magnetic resonance imaging and histology measurements of knee articular cartilage in a canine posterolateral knee injury model: a preliminary analysis.

    Science.gov (United States)

    Pepin, Scott R; Griffith, Chad J; Wijdicks, Coen A; Goerke, Ute; McNulty, Margaret A; Parker, Josh B; Carlson, Cathy S; Ellermann, Jutta; LaPrade, Robert F

    2009-11-01

    There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis. The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections. Controlled laboratory study. Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices. The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P .1). These results demonstrate that 7.0-T magnetic resonance imaging provides an alternative method to histology to evaluate early osteoarthritic changes in articular cartilage in a canine model by detecting increases in articular cartilage area. The noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo monitoring of osteoarthritis progression and intervention in animal models and humans for osteoarthritis.

  13. Articular cartilage scores in cranial cruciate ligament-deficient dogs with or without bucket handle tears of the medial meniscus.

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    Kaufman, Kathryn; Beale, Brian S; Thames, Howard D; Saunders, W Brian

    2017-01-01

    To compare articular cartilage scores in cranial cruciate ligament (CCL)-deficient dogs with or without concurrent bucket handle tears (BHT) of the medial meniscus. Retrospective case series. Client-owned dogs treated with arthroscopy and tibial plateau leveling osteotomy or extracapsular repair for complete CCL rupture (290 stifles from 264 dogs). Medical records and arthroscopic images were reviewed. Medial femoral condyle (MFC) and medial tibial plateau (MTP) cartilage was scored using the modified Outerbridge scale. Periarticular osteophytosis (PAO) and injury to the medial meniscus were recorded. Data were analyzed using Student's t-tests, Wilcoxon rank-sum test, and Fisher's exact test for changes in the stifle based on meniscal condition, body weight, and duration of lameness. PAO, MFC, and MTP articular cartilage scores were not significantly different in dogs with or without BHT. There were no significant differences in MFC or MTP scores when dogs were evaluated based on bodyweight and the presence or absence of a BHT. However, PAO formation was significantly increased in dogs weighing >13.6 kg and concurrent meniscal injury vs. dogs weighing <13.6 kg and concurrent meniscal injury (P < .001). Significantly more stifles with chronic lameness (40 of 89; 44.9%) had the highest PAO score of 2 reported compared to only 42 of 182 stifles (23.1%) with acute lameness (P < .001). The presence of a BHT of the medial meniscus was not associated with more severe arthroscopic articular cartilage lesions in the medial joint compartment at the time of surgery. © 2016 The American College of Veterinary Surgeons.

  14. Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2).

    Science.gov (United States)

    Sellers, R S; Zhang, R; Glasson, S S; Kim, H D; Peluso, D; D'Augusta, D A; Beckwith, K; Morris, E A

    2000-02-01

    Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the

  15. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis

    Science.gov (United States)

    McCulloch, R. S.; Ashwell, M. S.; Maltecca, C.; O'Nan, A. T.; Mente, P. L.

    2014-01-01

    An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading. PMID:25478225

  16. The intra-articular injection of RANKL-binding peptides inhibits cartilage degeneration in a murine model of osteoarthritis

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    Md. Zahirul Haque Bhuyan

    2017-06-01

    Full Text Available We recently found that the receptor activator of NF-κB ligand (RANKL-binding peptide, OP3-4 stimulated the differentiation of both chondrocytes and osteoblasts. OP3-4 is also shown to inhibit cartilage degeneration. To clarify whether the peptide can inhibit cartilage degeneration without stimulating bone formation, we first performed a proliferation assay using C3H10T1/2 (the murine mesenchymal stem cell line, which is the common origin of both chondrocytes and osteoblasts. The RANKL-binding peptides, OP3-4 and W9, promoted cellular proliferation at 24 and 48 h, respectively. Next, we injected both peptides into the intra-articular space of the knee joints of mice with monosodium-iodoacetate (MIA-induced osteoarthritis to clarify the effects of the peptides on cartilage tissue. Twenty-five nine-week-old male C57BL/6J mice received injections of vehicle, or the same molar amount of W9, OP3-4, or a control peptide (which could not stimulate osteoblast differentiation on days 7, 14, and 21 after the injection of MIA. The mice were sacrificed on day 28. The histomorphometric analyses revealed that both peptides inhibited the degeneration of cartilage without enhancing bone formation activity. Our data suggest that the stimulation of mesenchymal cell proliferation by the RANKL-binding peptides might lead to the inhibition of cartilage degeneration.

  17. Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection.

    Science.gov (United States)

    Langenmair, Elia R; Kubosch, Eva J; Salzmann, Gian M; Beck, Samuel; Schmal, Hagen

    2015-01-01

    Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n = 8) or with intact joints (n = 67). Cytokines and cell function were also analyzed using a human in vitro model of joint infection. Synovial IL-1β levels were significantly higher in patients with arthroplasty (p = 0.004). Higher IL-1β concentrations were also found in the in vitro model without chondrocytes (p < 0.05). The anti-inflammatory cytokines IL-4 and IL-10 were consistently expressed in vivo and in vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadily in vitro, reaching higher levels without chondrocytes (p < 0.05). Likewise, the viability of synovial fibroblasts (SFB) during infection was higher in the presence of chondrocytes. The cartilage-metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB. Our data suggest an anti-inflammatory effect of cartilage associated with the SFBs' increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS 00003536, MISSinG.

  18. Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

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    Elia R. Langenmair

    2015-01-01

    Full Text Available Objective. Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n = 8 or with intact joints (n = 67. Cytokines and cell function were also analyzed using a human in vitro model of joint infection. Results. Synovial IL-1β levels were significantly higher in patients with arthroplasty (p = 0.004. Higher IL-1β concentrations were also found in the in vitro model without chondrocytes (p < 0.05. The anti-inflammatory cytokines IL-4 and IL-10 were consistently expressed in vivo and in vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadily in vitro, reaching higher levels without chondrocytes (p < 0.05. Likewise, the viability of synovial fibroblasts (SFB during infection was higher in the presence of chondrocytes. The cartilage-metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB. Conclusions. Our data suggest an anti-inflammatory effect of cartilage associated with the SFBs’ increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS 00003536, MISSinG.

  19. Assessing the effect of football play on knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

    Science.gov (United States)

    Wei, Wenbo; Lambach, Becky; Jia, Guang; Flanigan, David; Chaudhari, Ajit M W; Wei, Lai; Rogers, Alan; Payne, Jason; Siston, Robert A; Knopp, Michael V

    2017-06-01

    The prevalence of cartilage lesions is much higher in football athletes than in the general population. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been shown to quantify regional variations of glycosaminoglycan (GAG) concentrations which is an indicator of early cartilage degeneration. The goal of this study is to determine whether dGEMRIC can be used to assess the influence in cartilage GAG concentration due to college level football play. Thirteen collegiate football players with one to four years of collegiate football play experience were recruited and both knee joints were scanned using a dedicated 8-channel phased array knee coil on a 3T MRI system. The contrast concentrations within cartilage were calculated based on the T 1 values from dGEMRIC scans. No substantial differences were found in the contrast concentrations between the pre- and post-season across all the cartilage compartments. One year collegiate football players presented an average contrast concentration at the pre-season of 0.116±0.011mM and post-season of 0.116±0.011mM. In players with multiple years of football play, contrast uptake was elevated to 0.141±0.012mM at the pre-season and 0.139±0.012mM at the post-season. The pre-season 0.023±0.016mM and post-season 0.025±0.016mM increase in contrast concentration within the group with multiple years of experience presented with a >20% increase in contrast uptake. This may indicate the gradual, cumulative damage of football play to the articular cartilage over years, even though the effect may not be noticeable after a season of play. Playing collegiate football for a longer period of time may lead to cartilage microstructural alterations, which may be linked to early knee cartilage degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Characterization of bovine cartilage by fiber Bragg grating-based stress relaxation measurements

    Science.gov (United States)

    Baier, V.; Marchi, G.; Foehr, P.; Burgkart, R.; Roths, J.

    2017-04-01

    A fiber-based device for testing mechanical properties of cartilage is presented within this study. The measurement principle is based on stepwise indentation into the tissue and observing of corresponding relaxation of the stress. The indenter tip is constituted of a cleaved optical fiber that includes a fiber Bragg grating which is used as the force sensor. Stress relaxation measurements at 25 different positions on a healthy bovine cartilage sample were performed to assess the behavior of healthy cartilage. For each indentation step a good agreement was found with a viscoelastic model that included two time constants. The model parameters showed low variability and a clear dependence with indentation depth. The parameters can be used as reference values for discriminating healthy and degenerated cartilage.

  1. High Kinesiophobia and Pain Catastrophizing in People with Articular Cartilage Defects in the Knee

    Science.gov (United States)

    Thoma, Louise M.; Flanigan, David C.; Best, Thomas M.; Schmitt, Laura

    2017-01-01

    Objectives: Psychosocial factors, including kinesiophobia and pain catastrophizing, are increasingly recognized for the role they play in knee function and quality of life for people with anterior cruciate ligament reconstruction (ACLR), knee osteoarthritis (OA), and total knee arthroplasties (TKA). People with articular cartilage defects in the knee have impaired function and poor quality of life, however the extent to which they present with kinesiophobia and pain catastrophizing is not known. The purpose of this study is to compare kinesiophobia, i.e. fear of movement-related pain/reinjury, and pain catastrophizing of people with articular cartilage defects (ACD) in the knee to healthy controls. Methods: Thirty-five individuals (19M:16F, Age mean ± 95%CI 29.8 ± 2.8 years old, BMI 28.1 ± 1.44) seeking surgical consultation for an ACD in the knee confirmed with 3.0T MRI and 18 controls (9M:9F, Age 29.8 ± 3.0 years old, BMI 24.9 ± 1.3) without history of knee injury participated in the study. Exclusion criteria included; age >55 years, BMI >35kg/m2, recent surgery, current low back pain or unrelated lower extremity pain, and history of spine surgery or neurological injury and pathology. Kinesiophobia for all 53 subjects was measured with the Tampa Scale of Kinesiophobia (TSK). The TSK was scored using the original 17-item (TSK-17, Min 17 - Max 68) and modified 11-item (TSK-11, Min 11 - Max 44) scoring systems as both have been commonly used in the literature. Pain catastrophizing was measured with the Pain Catastrophizing Scale (PCS, Min 0 - Max 52). Higher scores on these measures indicate greater kinesiophobia and pain catastrophizing. Independent t-tests were used to compare the ACD group to the healthy controls (α=0.05). Mean TSK and PCS scores (± 95% CI) were plotted alongside values published in samples with other knee pathologies for reference. Results: Participants with ACDs reported higher kinesiophobia (TSK-17 mean score ± 95%CI [range]: ACD 40

  2. Spaceflight-Relevant Challenges of Radiation and/or Reduced Weight Bearing Cause Arthritic Responses in Knee Articular Cartilage.

    Science.gov (United States)

    Willey, J S; Kwok, A T; Moore, J E; Payne, V; Lindburg, C A; Balk, S A; Olson, J; Black, P J; Walb, M C; Yammani, R R; Munley, M T

    2016-10-01

    acute degenerative and pre-arthritic changes in the knee articular cartilage of rats. A return to normal weight bearing resulted in some recovery from cartilage degradation. However, radiation delivered as both a single challenge and when combined with HLU resulted in chronic cartilage damage. These findings suggest that radiation exposure during spaceflight leads to and/or impairs recovery of cartilage upon return to reloading, generating long-term joint problems for astronauts.

  3. Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig.

    Science.gov (United States)

    Waller, Kimberly A; Chin, Kaitlyn E; Jay, Gregory D; Zhang, Ling X; Teeple, Erin; McAllister, Scott; Badger, Gary J; Schmidt, Tannin A; Fleming, Braden C

    2017-06-01

    Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been shown previously to be down-regulated after traumatic joint injury such as a meniscal tear. Preliminary evidence suggests that intra-articular injection of PRG4 after injury will reduce cartilage damage in rat models of surgically induced posttraumatic osteoarthritis. To determine the efficacy of intra-articular injection of full-length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscal destabilization (DMM) in a preclinical large animal model. Controlled laboratory study. Unilateral DMM was performed in 29 Yucatan minipigs. One week after DMM, animals received 3 weekly intra-articular injections (3 mL per injection): (1) rhPRG4 (1.3 mg/mL; n = 10); (2) rhPRG4+hyaluronan (1.3 mg/mL rhPRG4 and 3 mg/mL hyaluronan [~950 kDA]; n = 10); and (3) phosphate-buffered saline (PBS; n = 9). Hindlimbs were harvested 26 weeks after surgery. Cartilage integrity was evaluated by use of macroscopic (India ink) and microscopic (safranin O-fast green and hematoxylin and eosin) scoring systems. Secondary outcomes evaluated via enzyme-linked immunosorbent assay (ELISA) included PRG4 levels in synovial fluid, carboxy-terminal telepeptide of type II collagen (CTX-II) concentrations in urine and serum, and interleukin 1β (IL-1β) levels in synovial fluid and serum. The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared with the PBS group ( P = .002). No difference was found between the rhPRG4+hyaluronan and PBS groups ( P = .23). However, no differences in microscopic damage scores were observed between the 3 groups ( P = .70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared with the PBS group ( P = .033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared with the PBS ( P = .013) and rhPRG4+hyaluronan ( P

  4. Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs with low molecular weight hyaluronic acid (HA could promote regeneration of massive cartilage in rabbits. Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek. The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml were suspended in 0.5% low molecular weight HA (0.15 ml and injected into the left knee, and HA solution (0.30 ml alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days. Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage. Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

  5. Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair.

    Science.gov (United States)

    Lazarini, Mariana; Bordeaux-Rego, Pedro; Giardini-Rosa, Renata; Duarte, Adriana S S; Baratti, Mariana Ozello; Zorzi, Alessandro Rozim; de Miranda, João Batista; Lenz Cesar, Carlos; Luzo, Ângela; Olalla Saad, Sara Teresinha

    2017-10-01

    Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

  6. Clinically Relevant Subregions of Articular Cartilage of the Hip for Analysis and Reporting Quantitative Magnetic Resonance Imaging: A Technical Note.

    Science.gov (United States)

    Surowiec, Rachel K; Lucas, Erin P; Wilson, Katharine J; Saroki, Adriana J; Ho, Charles P

    2014-01-01

    Before quantitative imaging techniques can become clinically valuable, the method, and more specifically, the regions of locating and reporting these values should be standardized toward reproducibility comparisons across centers and longitudinal follow-up of individual patients. The purpose of this technical note is to describe a rigorous and reproducible method of locating, analyzing, and reporting quantitative MRI values in hip articular cartilage with an approach that is consistent with current orthopedic literature. To demonstrate this localization and documentation, 3 patients (age, 23 ± 5.1 years; 2 males, 1 female) who presented with symptomatic mixed-type femoroacetabular impingement (α angle, 63.3° ± 2.1°; center edge angle, 39° ± 4.2°) were evaluated with T2-mapping at 3 T MRI prior to hip arthroscopy. Manual segmentation was performed and cartilage of the acetabulum and femur was divided into 12 subregions adapted from the geographic zone method. Bone landmarks in the acetabulum and femur, identifiable both in arthroscopy and MR images, were manually selected and the coordinates exported for division of cartilage. Mean T2 values in each zone are presented. The current work outlines a standardized system to locate and describe quantitative mapping values that could aid in surgical decision making, planning, and the noninvasive longitudinal follow-up of implemented cartilage preservation and restoration techniques.

  7. Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading

    Directory of Open Access Journals (Sweden)

    Hai-Ying Liu

    2017-01-01

    Full Text Available COMSOL finite element software was used to establish a solid-liquid coupling biphasic model of articular cartilage and a microscopic model of chondrocytes, using modeling to take into account the shape and number of chondrocytes in cartilage lacuna in each layer. The effects of cyclic loading at different frequencies on the micromechanical environment of chondrocytes in different regions of the cartilage were studied. The results showed that low frequency loading can cause stress concentration of superficial chondrocytes. Moreover, along with increased frequency, the maximum value of stress response curve of chondrocytes decreased, while the minimum value increased. When the frequency was greater than 0.2 Hz, the extreme value stress of response curve tended to be constant. Cyclic loading had a large influence on the distribution of liquid pressure in chondrocytes in the middle and deep layers. The concentration of fluid pressure changed alternately from intracellular to peripheral in the middle layer. Both the range of liquid pressure in the upper chondrocytes and the maximum value of liquid pressure in the lower chondrocytes in the same lacunae varied greatly in the deep layer. At the same loading frequency, the elastic modulus of artificial cartilage had little effect on the mechanical environment of chondrocytes.

  8. A study on MR images of the articular cartilage in medial-type osteoarthritis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Hiroyuki; Ishii, Yoshiaki; Hayashi, Mitsutoshi; Kotani, Akihiro [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    2001-06-01

    Changes in the articular cartilage of 88 knees of 73 cases (age range 40-78) diagnosed clinically and radiologically as OA (osteoarthritis) were studied by obtaining fat-suppressed MR images of the knee. On 27 knees out of the 88, moreover, macroscopic observation was performed to make a comparative study between the directly-observed findings and MR findings. Fat-suppressed MR images were obtained sagittally by 3D-FLASH (fast low angle shot) sequence. The examined regions consisted of the following 4 sites; the medial condyle of the femur, its lateral condyle, the medial condyle of the tibia, and its lateral condyle. The revealed conditions of the cartilage were morphologically classified into 4 Stages. The evidence of cartilage defect on MR images was most frequently found at the medial condyle of the femur, with the medial condyle of the tibia, the lateral condyle of the femur, and the lateral condyle of the tibia following in a less frequent order. Fat-suppressed MRI's sensitivity to cartilage defect against macroscopy was 94.5%, specificity 95.4%, and accuracy 95.2%. MR imaging using fat-suppression can reveal cartilaginous degeneration and defect so well that this technique provides an important indication for selecting a proper method of treatment. (author)

  9. [Articular cartilage regenerative therapy with synovial mesenchymal stem cells in a pig model].

    Science.gov (United States)

    Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Kobayashi, Eiji

    2013-12-01

    Current therapies for cartilage injury remain some issues such as the quality of regenerated cartilage and its invasiveness. We have been trying to develop a low invasive treatment for cartilage regeneration with synovial mesenchymal stem cells (MSCs) . Here we introduce our preclinical study with miniature pigs whose knee joints are similar to those of humans in terms of size and cartilage metabolism. Cartilage defect was created at the weight bearing area of both porcine knee joints. Synovial MSCs were transplanted by delivering a synovial MSC suspension onto the cartilage defect of the one side and the knee was kept immobilized for 10 minutes. Sequential arthroscopic and histological observations showed the contribution of synovial MSCs after transplantation, and a better hyaline cartilaginous-tissue regeneration in the MSC-treated knees than in the non-treated control knees at 12 weeks. Based on this and other preclinical studies, we have started a clinical study for cartilage regeneration with autologous synovial MSCs.

  10. Monitoring of the degradation in the rat's articular cartilage inducing osteoarthritis using common-path Fourier-domain optical coherence tomography

    Science.gov (United States)

    Shin, D. H.; Park, S. H.; Kim, B. Y.; Lee, M. Y.; Baik, H. K.; Seo, J. H.; Kang, J. U.; Song, C. G.

    2013-03-01

    The objective of this experiment is to evaluate the utility and limitations of optical coherence tomography (OCT) for real-time, high-resolution structural analysis. We monitored the degradation of the rat's articular cartilage inducing osteoarthritis (OA) and the change of the rat's articular cartilage recovery by treatment medication, using our developed common-path Fourier-domain (CP-FD) OCT. Also, we have done a comparative analysis the rat's articular cartilage and OA grade. To observe the progression of OA, we induced OA by injecting the monosodium iodoacetate (MIA) into the right knee joint. After the injection of MIA, we sacrificed the rats at intervals of 3 days and obtained OCT and histological images. OCT and histological images showed the OA progress of similar pattern. These results illustrated the potential for non-invasive diagnosis about the grade of OA using CP-FD OCT.

  11. Evaluation of acoustical parameter sensitivity to age-related and osteoarthritic changes in articular cartilage using 50-MHz ultrasound.

    Science.gov (United States)

    Chérin, E; Saïed, A; Laugier, P; Netter, P; Berger, G

    1998-03-01

    The current study reports the sensitivity of acoustical parameters estimated at high frequency to the osteoarthritic morphological and structural changes in patellar cartilage in rat knees. Osteoarthritis (OA) was induced by a single intra-articular injection of mono-iodo-acetic acid in right knees. OA patellas and their contralateral controls were excised at regular intervals after injection and were examined in vitro with a scanning acoustical microscope operating with a poly(vinylidene di-fluoride) (PVDF) 80-MHz focused transducer. Cartilage thickness was estimated using B-scan images. The quantitative analysis of the radiofrequency signal backscattered by the cartilage was performed using integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB), which were estimated in the 20-60-MHz frequency range. One week after injection, a cartilage thickness decrease was detected (-6%, on average) that preceded the significant hypertrophy (20.1%) that occurred 2 weeks after injection and could be due to tissue repair. From 1 week to 3 weeks after injection, the IRC of OA patellas was significantly lower than that of control patellas. The IRC difference increased with time from -3.3 +/- 2.4 dB at 1 week to -8.4 +/- 1.7 dB at 3 weeks. An AIB decrease was observed with time for both OA and control patellas (-2.9 to -4.2 dB per week). An AIB difference between OA and control patellas was detected from 1 week to 3 weeks after injection. This difference decreased with time. IRC variation reflects a change in acoustical impedance of the superficial layer of the cartilage and could be linked to a change in constituent content and/or to a disruption of fibers of the collagen network that led to the fibrillation of the cartilage surface. AIB variation reflects a change in shape, size and/or density of the scatterers and could be related to changes in the constituent content and in the organization of the matrix in the internal layer of the cartilage. IRC and

  12. Co-culture systems-based strategies for articular cartilage tissue engineering.

    Science.gov (United States)

    Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

    2018-03-01

    Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

  13. Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels

    National Research Council Canada - National Science Library

    Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A; Saris, Daniel B; Malda, J; Anseth, Kristi S; Gill, Thomas J; Randolph, Mark A

    2016-01-01

    ...) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM...

  14. Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults.

    Directory of Open Access Journals (Sweden)

    Sam Van Rossom

    Full Text Available Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading.

  15. Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

    Science.gov (United States)

    Kokkonen, H T; Chin, H C; Töyräs, J; Jurvelin, J S; Quinn, T M

    2017-04-01

    Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

  16. Comparison of MRI T2 relaxation changes of knee articular cartilage before and after running between young and old amateur athletes.

    Science.gov (United States)

    Cha, Jang Gyu; Lee, Jae Chul; Kim, Hyun Joo; Han, Jong Kyu; Lee, Eun Hye; Kim, Yong Dai; Jeon, Chan Hong

    2012-01-01

    To compare changes in T2 relaxation on magnetic resonance (MR) images of knee articular cartilage in younger and older amateur athletes before and after running. By using a 3.0-T MR imager, quantitative T2 maps of weight-bearing femoral and tibial articular cartilages in 10 younger and 10 older amateur athletes were acquired before, immediately after, and 2 hours after 30 minutes of running. Changes in global cartilage T2 signals of the medial and lateral condyles of the femur and tibia and regional cartilage T2 signals in the medial condyles of femoral and tibia in response to exercise were compared between the two age groups. Changes in global cartilage T2 values after running did not differ significantly between the age groups. In terms of the depth variation, relatively higher T2 values in the older group than in the younger group were observed mainly in the superficial layers of the femoral and tibial cartilage (p < 0.05). Age-related cartilage changes may occur mainly in the superficial layer of cartilage where collagen matrix degeneration is primarily initiated. However, no trend is observed regarding a global T2 changes between the younger and older age groups in response to exercise.

  17. Comparison of MRI T2 Relaxation Changes of Knee Articular Cartilage before and after Running between Young and Old Amateur Athletes

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jang Gyu; Jeon, Chan Hong; Lee, Eun Hye [Dept. of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of); Lee, Jae Chul; Kim, Hyun Joo [Soonchunhyang University College of Medicine, Seoul Hospital, Seoul (Korea, Republic of); Han, Jong Kyu [Dept. of Radiology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan (Korea, Republic of); Kim, Yong Dai [Dept. of Statistics, College of Natural Sciences, Seoul National University, Seoul (Korea, Republic of)

    2012-09-15

    To compare changes in T2 relaxation on magnetic resonance (MR) images of knee articular cartilage in younger and older amateur athletes before and after running. By using a 3.0-T MR imager, quantitative T2 maps of weight-bearing femoral and tibial articular cartilages in 10 younger and 10 older amateur athletes were acquired before, immediately after, and 2 hours after 30 minutes of running. Changes in global cartilage T2 signals of the medial and lateral condyles of the femur and tibia and regional cartilage T2 signals in the medial condyles of femoral and tibia in response to exercise were compared between the two age groups. Changes in global cartilage T2 values after running did not differ significantly between the age groups. In terms of the depth variation, relatively higher T2 values in the older group than in the younger group were observed mainly in the superficial layers of the femoral and tibial cartilage (p < 0.05). Age-related cartilage changes may occur mainly in the superficial layer of cartilage where collagen matrix degeneration is primarily initiated. However, no trend is observed regarding a global T2 changes between the younger and older age groups in response to exercise.

  18. High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

    Directory of Open Access Journals (Sweden)

    Sheila Laverty

    2015-04-01

    Full Text Available We studied changes in articular calcified cartilage (ACC and subchondral bone (SCB in the third carpal bones (C3 of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA. Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT image sets for the presence of high-density mineral infill (HDMI in ACC cracks and possible high-density mineralized protrusions (HDMP from the ACC mineralizing (tidemark front (MF into hyaline articular cartilage (HAC. We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA.

  19. Cartilage Regeneration in Full-Thickness Patellar Chondral Defects Treated with Particulated Juvenile Articular Allograft Cartilage: An MRI Analysis.

    Science.gov (United States)

    Grawe, Brian; Burge, Alissa; Nguyen, Joseph; Strickland, Sabrina; Warren, Russell; Rodeo, Scott; Shubin Stein, Beth

    2017-10-01

    Background Full-thickness cartilage lesions of the patella represent a common source of pain and dysfunction. Previously reported surgical treatment options include marrow stimulation, cell-based treatments, and osteochondral transfer. Minced juvenile allograft cartilage is a novel treatment option that allows for a single stage approach for these lesions. Hypothesis Particulated juvenile allograft cartilage (PJAC) for the treatment of chondral defects of the patella would offer acceptable lesion fill rates, mature over time, and not be associated with any negative biologic effects on the surrounding tissue. Methods A retrospective chart review of prospectively collected data was conducted to identify consecutive patients who were treated with PJAC for a full thickness symptomatic cartilage lesion. Qualitative (fast spin echo) and quantitative (T2 mapping) magnetic resonance imaging (MRI) was undertaken at the 6-, 12-, and 24-month postoperative mark. Numerous patient, lesion, and graft specific factors were assessed against MRI scores and percent defect fill of the graft. Graft maturation over time was also assessed. Results Forty-five patients total were included in the study. Average age at the time of surgery was 26.5 years (range 13-45 years), average lesion size was 208 mm(2) (range 4-500 mm(2)), and average donor age was 49.5 months (range 3-120 months). Sixty percent of the patients were female, while 93% of all patients underwent a concomitant procedure at the time of the index operation. Six-month MRI findings revealed that no patient-, graft-, or donor-specific factors correlated with MR scores, and 82% of the knees demonstrated good to excellent fill. Twelve-month MRI findings revealed that T2 relaxation times of deep graft demonstrated negative correlation with patient age ( P = 0.049) and donor age ( P = 0.006), the integration zone showed a negative correlation with donor age ( P = 0.026). In all, 85% of patients at 12 months displayed good to

  20. Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI

    Science.gov (United States)

    Wang, Nian; Xia, Yang

    2013-10-01

    A number of experimental issues in the measurement of multi-component T2 and T1ρ relaxations in native and enzymatically digested articular cartilage were investigated by microscopic MRI (μMRI). The issues included the bath solutions (physiological saline and phosphate buffered saline (PBS)), the imaging resolution (35-140 μm), the specimen orientations (0° and 55°), and the strength of spin-lock frequencies (0.5-2 kHz) in the T1ρ experiments. In addition to cartilage, the samples of agar gel and doped water solution were also used in the investigation. Two imaging sequences were used: CPMG-SE and MSME. All raw data were analyzed by the non-negative least square (NNLS) method. The MSME sequence was shown to result in the observation of multi-component T2, even in the gel and liquid samples, demonstrating the artificial uncleanness of this sequence in the multi-component measurements. The soaking of cartilage in PBS reduced the observable T2 components to one at both 0° and 55°, suggesting the effect of phosphate ions on proton exchange between different pools of water molecules. The cartilage orientation with respect to the external magnetic field and the spin-lock strengths in the T1ρ experiment both affected the quantification of the multi-component relaxation. The transitions between a mono-component and multi-components in cartilage under various experimental conditions call for the extra caution in interpreting the relaxation results.

  1. Engineering of rat articular cartilage on porous sponges: effects of tgf-beta 1 and microgravity bioreactor culture.

    Science.gov (United States)

    Emin, Nuray; Koç, Aysel; Durkut, Serap; Elçin, A Eser; Elçin, Y Murat

    2008-01-01

    The objective of this study was to develop an engineered rat hyaline cartilage by culturing articular chondrocytes on three-dimensional (3D) macroporous poly(DL-lactic-co-glycolic acid) (PLGA) sponges under chondrogenic induction and microgravity bioreactor conditions. Experimental groups consisted of 3D static and dynamic cultures, while a single cell monolayer (2D) served as the control. The effect of seeding conditions (static vs. dynamic) on cellularization of the scaffolds was investigated. MTT assay was used to evaluate the number of viable cells in each group at different time points. Formation of a hyaline-like cartilage was evaluated for up to 4 weeks in vitro. While 2D culture resulted in cell sheets with very poor matrix production, 3D culture was in the favor of tissue formation. A higher yield of cell attachment and spatially uniform cell distribution was achieved when dynamic seeding technique was used. Dynamic culture promoted cell growth and infiltration throughout the sponge structure and showed the formation of cartilage tissue, while chondrogenesis appeared attenuated more towards the outer region of the constructs in the static culture group. Medium supplemented with TGF-beta 1 (5 ng/ml) had a positive impact on proteoglycan production as confirmed by histochemical analyses with Alcian blue and Safranin-O stainings. Formation of hyaline-like tissue was demonstrated by immunohistochemistry performed with antibodies against type II collagen and aggrecan. SEM confirmed higher level of cellularization and cartilage tissue formation in bioreactor cultures induced by TGF-beta 1. The data suggest that PLGA sponge inside rotating bioreactor with chondrogenic medium provides an environment that mediates isolated rat chondrocytes to redifferentiate and form hyaline-like rat cartilage, in vitro.

  2. Microfracture and osteochondral autograft transplantation are cost-effective treatments for articular cartilage lesions of the distal femur.

    Science.gov (United States)

    Miller, D Josh; Smith, Matthew V; Matava, Matthew J; Wright, Rick W; Brophy, Robert H

    2015-09-01

    Multiple techniques have been suggested for the treatment of isolated knee articular cartilage injuries. For smaller lesions (purpose of this study was to analyze the costs and outcomes of microfracture and OAT to compare their cost-effectiveness. The hypothesis was that microfracture would be more cost-effective. Economic and decision analysis; Level of evidence, 2. A literature search was performed to identify studies comparing microfracture and OAT for the treatment of articular cartilage lesions of the distal femur in an adult population. Data from these studies including surgical time, failure rates, revision surgeries, outcome scores, and return to athletics were then incorporated into a constructed cost model using standard accounting methodology. The model was based on actual 2013 cost figures (in US dollars) for all procedure, operating room, and instrumentation costs. Three studies, with a mean follow-up of 8.7 years, met the inclusion criteria of having evidence level 1 or 2 comparing microfracture and OAT. There was a cumulative 28.6% reoperation rate among patients undergoing microfracture compared with 12.5% among patients undergoing OAT. While both groups demonstrated significant improvements compared with preoperative levels, the only significant differences in any outcome score reported between the 2 procedures were the International Cartilage Repair Society (ICRS) score and patient-reported return to their previous sports activity level. While microfracture had a lower initial cost ($3100), these savings lessened over 1 year ($1843) and 10 years ($996). Microfracture was more cost-effective when comparing Lysholm and Hospital for Special Surgery scores, whereas OAT was more cost-effective when comparing Tegner and ICRS scores. There was a significantly lower cost for return to play in athletes after OAT versus microfracture at 1 year ($11,428 vs $16,953, respectively), 3 years ($12,856 vs $38,000, respectively), and 10 years ($32,141 vs $60

  3. Are Articular Cartilage Lesions and Meniscus Tears Predictive of IKDC, KOOS, and Marx Activity Level Outcomes after ACL Reconstruction? A 6-Year Multicenter Cohort Study

    Science.gov (United States)

    Cox, Charles L.; Huston, Laura J.; Dunn, Warren R.; Reinke, Emily K.; Nwosu, Samuel K.; Parker, Richard D.; Wright, Rick W.; Kaeding, Christopher C.; Marx, Robert G.; Amendola, Annunziata; McCarty, Eric C.; Wolf, Brian R.; Harrell, Frank E.; Spindler, Kurt P.

    2014-01-01

    Background Identifying risk factors for inferior outcomes after ACL reconstruction (ACLR) is important for prognosis and future treatment. The goal of this study was to determine whether articular cartilage and meniscal variables are predictive of 3 validated sports outcome instruments after ACLR. Hypothesis/Purpose We hypothesized that articular cartilage lesions and meniscus tears/treatment would be predictors of the IKDC, KOOS (all 5 subscales), and Marx activity level at 6 years following ACLR. Study Design Prospective cohort, Level 1 Methods Between 2002 and 2004, 1512 ACLR subjects were prospectively enrolled and followed longitudinally with the IKDC, KOOS, and Marx activity score completed at entry, 2, and 6 years. A logistic regression model was built incorporating variables from patient demographics, surgical technique, articular cartilage injuries, and meniscus tears/treatment to determine the predictors (risk factors) of IKDC, KOOS, and Marx at 6 years. Results We completed a minimum follow-up on 86% (1307/1512) of our cohort at 6 years. The cohort was 56% male, had a median age of 23 years at the time of enrollment, with 76% reporting a non-contact injury mechanism. Incidence of concomitant pathology at the time of surgery consisted of the following: articular cartilage (medial femoral condyle [MFC]-25%, lateral femoral condyle [LFC]-20%, medial tibial plateau [MTP]-6%, lateral tibial plateau [LTP]-12%, patella-20%, trochlear-9%) and meniscal (medial-38%, lateral-46%). Both articular cartilage lesions and meniscal tears were significant predictors of 6-year outcomes on IKDC and KOOS. Grade 3 or 4 articular cartilage lesions (excluding patella) significantly reduced IKDC and KOOS scores at 6 years. IKDC demonstrated worse outcomes with the presence of a grade 3-4 chondral lesion on the MFC, MTP, and LFC. Likewise, KOOS was negatively affected by cartilage injury. The sole significant predictor of reduced Marx activity was the presence of a grade 4 lesion

  4. Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels

    NARCIS (Netherlands)

    Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A.; Saris, Daniel B.; Malda, J; Anseth, Kristi S.; Gill, Thomas J.; Randolph, Mark A.

    2016-01-01

    Background: Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to

  5. Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels

    NARCIS (Netherlands)

    Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A; Saris, Daniel B; Malda, Jos; Anseth, Kristi S; Gill, Thomas J; Randolph, Mark A

    2016-01-01

    BACKGROUND: Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to

  6. Caprine articular, meniscus and intervertebral disc cartilage : An integral analysis of collagen network and chondrocytes

    NARCIS (Netherlands)

    Vonk, Lucienne A.; Kroeze, Robert Jan; Doulabi, Behrouz Zandieh; Hoogendoorn, Roel J.; Huang, ChunLing; Helder, Marco N.; Everts, Vincent; Bank, Ruud A.

    Cartilage is a tissue with only limited reparative capacities. A small part of its volume is composed of cells, the remaining part being the hydrated extracellular matrix (ECM) with collagens and proteoglycans as its main constituents. The functioning of cartilage depends heavily on its ECM.

  7. Caprine articular, meniscus and intervertebral disc cartilage: an integral analysis of collagen network and chondrocytes

    NARCIS (Netherlands)

    Vonk, L.A.; Kroeze, R.J.; Doulabi, B.Z.; Hoogendoorn, R.J.; Huang, C.; Helder, M.N.; Everts, V.; Bank, R.A.

    2010-01-01

    Cartilage is a tissue with only limited reparative capacities. A small part of its volume is composed of cells, the remaining part being the hydrated extracellular matrix (ECM) with collagens and proteoglycans as its main constituents. The functioning of cartilage depends heavily on its ECM.

  8. QUANTITATIVE MAGNETIC RESONANCE IMAGING OF ARTICULAR CARTILAGE AND ITS CLINICAL APPLICATIONS

    Science.gov (United States)

    Li, Xiaojuan; Majumdar, Sharmila

    2013-01-01

    Cartilage is one of the most essential tissues for healthy joint function and is compromised in degenerative and traumatic joint diseases. There have been tremendous advances during the past decade using quantitative MRI techniques as a non-invasive tool for evaluating cartilage, with a focus on assessing cartilage degeneration during osteoarthritis (OA). In this review, after a brief overview of cartilage composition and degeneration, we discuss techniques that grade and quantify morphologic changes as well as the techniques that quantify changes in the extracellular matrix. The basic principles, in vivo applications, advantages and challenges for each technique are discussed. Recent studies using the OA Initiative (OAI) data are also summarized. Quantitative MRI provides non-invasive measures of cartilage degeneration at the earliest stages of joint degeneration, which is essential for efforts towards prevention and early intervention in OA. PMID:24115571

  9. Articular cartilage damage with intramedullary lesion (bone bruise) in anterior cruciate ligament rupture

    Energy Technology Data Exchange (ETDEWEB)

    Ide, Shuya; Ohdera, Toshihiro; Tokunaga, Masami; Hiroshima, Shiro; Yoshimoto, Eiji [Fukuoka Orthopaedic Hospital (Japan)

    2002-09-01

    We evaluated the relationship between the intramedullary lesion on MRI and cartilage damage in patients associated with acute anterior cruciate ligament (ACL) rupture. Thirty-two cases documented by MRI and arthroscopy within one month from injury underwent ACL reconstruction using ST-G, and arthroscopy was performed again after surgery. The mean term between reconstruction and postoperative arthroscopy was twelve months. The cartilage damage on arthroscopy was compared with the intramedullary lesion on MRI. Cartilage damage was observed in 9 cases (28.1%) during the initial arthroscopy and in 16 cases (50.0%) during the second arthroscopy. Intramedullary lesion was detected in all 32 cases (total: 73 lesions) on MRI. Intramedullary lesion leading to cartilage damage was common in the geographic-type lateral femoral condyle. There was significant difference between the lateral meniscus tear and the cartilage damage of the lateral compartment. (author)

  10. Morphological and Microstructural Alterations of the Articular Cartilage and Bones during Treadmill Exercises with Different Additional Weight-Bearing Levels

    Directory of Open Access Journals (Sweden)

    Jiazi Gao

    2017-01-01

    Full Text Available The aim of this study was to investigate the morphological and microstructural alterations of the articular cartilage and bones during treadmill exercises with different exercise intensities. Sixty 5-week-old female rats were randomly divided into 10 groups: five additional weight-bearing groups (WBx and five additional weight-bearing with treadmill exercise groups (EBx, which were subjected to additional weight bearing of x% (x = 0, 5, 12, 19, and 26 of the corresponding body weight of each rat for 15 min/day. After 8 weeks of experiment, the rats were humanely sacrificed and their bilateral intact knee joints were harvested. Morphological analysis of the cartilages and microcomputed tomography evaluation of bones were subsequently performed. Results showed that increased additional weight bearing may lead to cartilage damage. No significant difference was observed among the subchondral cortical thicknesses of the groups. The microstructure of subchondral trabecular bone of 12% and 19% additional weight-bearing groups was significantly improved; however, the WB26 and EB26 groups showed low bone mineral density and bone volume fraction as well as high structure model index. In conclusion, effects of treadmill exercise on joints may be associated with different additional weight-bearing levels, and exercise intensities during joint growth and maturation should be selected reasonably.

  11. Nanomechanics of Engineered Articular Cartilage: Synergistic Influences of Transforming Growth Factor-β3 and Oscillating Pressure.

    Science.gov (United States)

    Nazempour, Arshan; Quisenberry, Chrystal R; Van Wie, Bernard J; Abu-Lail, Nehal I

    2016-03-01

    Articular cartilage (AC), tissue with the lowest volumetric cellular density, is not supplied with blood and nerve tissue resulting in limited ability for self-repair upon injury. Because there is no treatment capable of fully restoring damaged AC, tissue engineering is being investigated. The emphasis of this field is to engineer functional tissues in vitro in bioreactors capable of mimicking in vivo envi- ronments required for appropriate cellular growth and differentiation. In a step towards engineering AC, human adipose-derived stem cells were differentiated in a unique centrifugal bioreactor under oscillating hydrostatic pressure (OHP) and supply of transforming growth factor beta 3 (TGF-β3) that mimic in vivo environments. Static micromass and pellet cultures were used as controls. Since withstanding and absorbing loads are among the main functions of an AC, mechanical properties of the engineered AC tissues were assayed using atomic force microscopy (AFM) under a controlled indentation depth of 100 nm. Young's moduli of elasticity were quantified by modeling AFM force-indentation data using the Hertz model of contact mechanics. We found exposure to OHP causes cartilage constructs to have 45-fold higher Young's moduli compared to static cultures. Addition of TGF-β3 further increases Young's moduli in bioreactor samples by 1.9-fold bringing it within 70.6% of the values estimated for native cartilage. Our results imply that OHP and TGF-β3 act synergistically to improve the mechanics of engineered tissues.

  12. Radiographic evaluation of feline appendicular degenerative joint disease vs. Macroscopic appearance of articular cartilage.

    Science.gov (United States)

    Freire, Mila; Robertson, Ian; Bondell, Howard D; Brown, James; Hash, Jon; Pease, Anthony P; Lascelles, B Duncan X

    2011-01-01

    Degenerative joint disease (DJD) is common in domesticated cats. Our purpose was to describe how radiographic findings thought to indicate feline DJD relate to macroscopic cartilage degeneration in appendicular joints. Thirty adult cats euthanized for reasons unrelated to this study were evaluated. Orthogonal digital radiographs of the elbow, tarsus, stifle, and coxofemoral joints were evaluated for the presence of DJD. The same joints were dissected for visual inspection of changes indicative of DJD and macroscopic cartilage damage was graded using a Total Cartilage Damage Score. When considering all joints, there was statistically significant fair correlation between cartilage damage and the presence of osteophytes and joint-associated mineralizations, and the subjective radiographic DJD score. Most correlations were statistically significant when looking at the different joints individually, but only the correlation between the presence of osteophytes and the subjective radiographic DJD score with the presence of cartilage damage in the elbow and coxofemoral joints had a value above 0.4 (moderate correlation). The joints most likely to have cartilage damage without radiographic evidence of DJD are the stifle (71% of radiographically normal joints) followed by the coxofemoral joint (57%), elbow (57%), and tarsal joint (46%). Our data support radiographic findings not relating well to cartilage degeneration, and that other modalities should be evaluated to aid in making a diagnosis of feline DJD. © 2011 Veterinary Radiology & Ultrasound.

  13. Bone morphogenetic proteins and articular cartilage: To serve and protect or a wolf in sheep clothing's?

    NARCIS (Netherlands)

    Kraan, P.M. van der; Davidson, E.N.; Berg, W.B. van den

    2010-01-01

    OBJECTIVE: Alterations in chondrocyte differentiation and matrix remodeling play a central role in osteoarthritis (OA). Chondrocyte differentiation and remodeling are amongst others regulated by the so-called Bone Morphogenetic Proteins (BMPs). Although BMPs are considered protective for articular

  14. POROUS POLYMER IMPLANTS FOR REPAIR OF FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE - AN EXPERIMENTAL-STUDY IN RABBIT AND DOG

    NARCIS (Netherlands)

    JANSEN, HWB; VETH, RPH; NIELSEN, HKL; DEGROOT, JH; PENNINGS, AJ

    1992-01-01

    Full-thickness defects of articular cartilage were repaired by implantation of porous polymer implants in rabbits and dogs. The quality of the repair tissue was determined by collagen typing with antibodies. Implants with varying pore sizes and chemical composition were used. The effect of loading

  15. Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects--a study in rabbits.

    NARCIS (Netherlands)

    Buma, P.; Pieper, J.S.; Tienen, Tony van; Susante, J.L.C. van; Kraan, P.M. van der; Veerkamp, J.H.; Berg, W.B. van den; Veth, R.P.H.; Kuppevelt, A.H.M.S.M. van

    2003-01-01

    The physico-chemical properties of collagenous matrices may determine the tissue response after insertion into full-thickness articular cartilage defects. In this study, cross-linked type I and type II collagen matrices, with and without attached chondroitin sulfate, were implanted into

  16. Delayed Gadolinium-Enhanced Magnetic Resonance Imaging (dGEMRIC) of Hip Joint Cartilage: Better Cartilage Delineation after Intra-Articular than Intravenous Gadolinium Injection

    DEFF Research Database (Denmark)

    Boesen, M.; Jensen, K.E.; Quistgaard, E.

    2006-01-01

    PURPOSE: To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. MATERIAL AND METHODS: In 10 patients (50% males, mean age 58...... years) with clinical and radiographic hip osteoarthritis (OA; Kellgren score II-III), MRI of the hip was performed twice on a clinical 1.5T MR scanner: On day 1, before and 90-180 min after 0.3 mmol/kg body weight i.v. Gd-DTPA and, on day 8, 90-180 min after ultrasound-guided i.a. injection of a 4 mmol....../l Gd-DTPA solution. Coronal STIR, coronal T1 fat-saturated spin-echo, and a cartilage-sensitive gradient-echo sequence (3D T1 SPGR) in the sagittal plane were applied. RESULTS Both the post-i.v. and post-i.a. Gd-DTPA images showed significantly higher signal-to-noise (SNR) and contrast-to-noise (CNR...

  17. Dynamic compressive properties of bovine knee layered tissue

    Science.gov (United States)

    Nishida, Masahiro; Hino, Yuki; Todo, Mitsugu

    2015-09-01

    In Japan, the most common articular disease is knee osteoarthritis. Among many treatment methodologies, tissue engineering and regenerative medicine have recently received a lot of attention. In this field, cells and scaffolds are important, both ex vivo and in vivo. From the viewpoint of effective treatment, in addition to histological features, the compatibility of mechanical properties is also important. In this study, the dynamic and static compressive properties of bovine articular cartilage-cancellous bone layered tissue were measured using a universal testing machine and a split Hopkinson pressure bar method. The compressive behaviors of bovine articular cartilage-cancellous bone layered tissue were examined. The effects of strain rate on the maximum stress and the slope of stress-strain curves of the bovine articular cartilage-cancellous bone layered tissue were discussed.

  18. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

    Science.gov (United States)

    McAlindon, Timothy E; LaValley, Michael P; Harvey, William F; Price, Lori Lyn; Driban, Jeffrey B; Zhang, Ming; Ward, Robert J

    2017-05-16

    Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone. To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain. Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015. Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years. Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94). Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of -0.21 mm vs -0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95% CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group

  19. Nanopolymers Delivery of the Bone Morphogenetic Protein-4 Plasmid to Mesenchymal Stem Cells Promotes Articular Cartilage Repair In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Junjun Shi

    2012-01-01

    Full Text Available The clinical application of viral vectors for gene therapy is limited for biosafety consideration. In this study, to promote articular cartilage repair, poly (lactic-co glycolic acid (PLGA nanopolymers were used as non-viral vectors to transfect rabbit mesenchymal stem cells (MSCs with the pDC316-BMP4-EGFP plasmid. The cytotoxicity and transfection efficiency in vitro were acceptable measuring by CCK-8 and flow cytometry. After transfection, Chondrogenic markers (mRNA of Col2a1, Sox9, Bmp4, and Agg of experimental cells (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers were increased more than those of control cells (MSCs being transfected with naked BMP-4 plasmid alone. In vivo study, twelve rabbits (24 knees with large full thickness articular cartilage defects were randomly divided into the experimental group (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers and the control group (MSCs being transfected with naked BMP-4 plasmid. The experimental group showed better regeneration than the control group 6 and 12 weeks postoperatively. Hyaline-like cartilage formed at week 12 in the experimental group, indicating the local delivery of BMP-4 plasmid to MSCs by PLGA nanopolymers improved articular cartilage repair significantly. PLGA nanopolymers could be a promising and effective non-viral vector for gene therapy in cartilage repair.

  20. Intra-articular therapy with recombinant human GDF5 arrests disease progression and stimulates cartilage repair in the rat medial meniscus transection (MMT) model of osteoarthritis.

    Science.gov (United States)

    Parrish, W R; Byers, B A; Su, D; Geesin, J; Herzberg, U; Wadsworth, S; Bendele, A; Story, B

    2017-04-01

    Investigation of osteoarthritis (OA) risk alleles suggests that reduced levels of growth and differentiation factor-5 (GDF5) may be a precipitating factor in OA. We hypothesized that intra-articular recombinant human GDF5 (rhGDF5) supplementation to the OA joint may alter disease progression. A rat medial meniscus transection (MMT) joint instability OA model was used. Animals received either one intra-articular injection, or two or three bi-weekly intra-articular injections of either 30 μg or 100 μg of rhGDF5 beginning on day 21 post surgery after structural pathology had been established. Nine weeks after MMT surgery, joints were processed for histological analysis following staining with toluidine blue. Control groups received intra-articular vehicle injections, comprising a glycine-buffered trehalose solution. OA changes in the joint were evaluated using histopathological end points that were collected by a pathologist who was blinded to treatment. Intra-articular rhGDF5 supplementation reduced cartilage lesions on the medial tibial plateau in a dose-dependent manner when administered therapeutically to intercept OA disease progression. A single 100 μg rhGDF5 injection on day 21 slowed disease progression at day 63. A similar effect was achieved with two bi-weekly injections of 30 μg. Two bi-weekly injections of 100 μg or three bi-weekly injections of 30 μg stopped progression of cartilage lesions. Importantly, three biweekly injections of 100 μg rhGDF5 stimulated significant cartilage repair. Intra-articular rhGDF5 supplementation can prevent and even reverse OA disease progression in the rat MMT OA model. Collectively, these results support rhGDF5 supplementation as an intra-articular disease modifying OA therapy. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Three-point Dixon chemical-shift imaging for evaluating articular cartilage defects in the knee joint on a low-field-strength open magnet.

    Science.gov (United States)

    Bredella, M A; Losasso, C; Moelleken, S C; Huegli, R W; Genant, H K; Tirman, P F

    2001-12-01

    The purpose of our study was to assess the value of a modified three-point Dixon MR technique for evaluating articular cartilage defects in the knee joint on a low-field-strength open magnet, correlated with arthroscopy. Twenty consecutive patients who underwent both MR imaging and arthroscopy of the knee joint for suspected internal derangement were examined. A modified three-point Dixon MR sequence with a single radiofrequency echo single-scan method for water and fat separation with correction of the static field inhomogeneities was performed on a 0.35-T open magnet to obtain fat suppression. The MR images were prospectively evaluated for the presence and grade of articular cartilage defects. Uniform fat suppression was obtained in all patients using the modified three-point Dixon technique. Fifty-nine cartilage abnormalities were identified in 19 patients on the basis of arthroscopy. Forty-seven of 59 arthroscopically proven abnormalities were prospectively detected on MR imaging. Compared with arthroscopy, the overall sensitivity of the modified three-point Dixon technique in detecting cartilage lesions was 80% and the specificity was 73%. Sixty-five percent of the cartilage abnormalities were graded identically on MR imaging and arthroscopy. The modified three-point Dixon sequence is a useful technique for achieving fat suppression in the knee joint on a 0.35-T open magnet. It is a sensitive and specific technique for the assessment of cartilage abnormalities in the knee.

  2. Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis.

    Science.gov (United States)

    Mirza, Eraj Humayun; Pan-Pan, Chong; Wan Ibrahim, Wan Mohd Azhar Bin; Djordjevic, Ivan; Pingguan-Murphy, Belinda

    2015-11-01

    Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic environment. © 2015 Wiley Periodicals, Inc.

  3. Are articular cartilage lesions and meniscus tears predictive of IKDC, KOOS, and Marx activity level outcomes after anterior cruciate ligament reconstruction? A 6-year multicenter cohort study.

    Science.gov (United States)

    Cox, Charles L; Huston, Laura J; Dunn, Warren R; Reinke, Emily K; Nwosu, Samuel K; Parker, Richard D; Wright, Rick W; Kaeding, Christopher C; Marx, Robert G; Amendola, Annunziata; McCarty, Eric C; Spindler, Kurt P

    2014-05-01

    Identifying risk factors for inferior outcomes after anterior cruciate ligament reconstruction (ACLR) is important for prognosis and future treatment. Articular cartilage lesions and meniscus tears/treatment would predict International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score (KOOS) (all 5 subscales), and Marx activity level at 6 years after ACLR. Cohort study (prognosis); Level of evidence, 1. Between 2002 and 2004, a total of 1512 ACLR patients were prospectively enrolled and followed longitudinally, with the IKDC, KOOS, and Marx activity score completed at entry, 2 years, and 6 years. A logistic regression model was built incorporating variables from patient demographics, surgical technique, articular cartilage injuries, and meniscus tears/treatment to determine the predictors (risk factors) of IKDC and KOOS scores and Marx activity level at 6 years. A minimum follow-up on 86% (1307/1512) of the cohort was completed at 6 years. The cohort was 56% male and had a median age of 23 years at the time of enrollment, with 76% reporting a noncontact injury mechanism. Incidence of concomitant injury at the time of surgery consisted of the following: articular cartilage (medial femoral condyle [MFC], 25%; lateral femoral condyle [LFC] 20%; medial tibial plateau [MTP], 6%; lateral tibial plateau [LTP], 12%; patella, 20%; trochlear, 9%) and meniscus (medial, 38%; lateral, 46%). Both articular cartilage lesions and meniscus tears were significant predictors of 6-year outcomes on the IKDC and KOOS. Grade 3 or 4 articular cartilage lesions (excluding patella) significantly reduced IKDC and KOOS scores at 6 years. The IKDC demonstrated worse outcomes with the presence of a grade 3 or 4 chondral lesion on the MFC, MTP, and LFC. Likewise, the KOOS score was negatively affected by cartilage injury. The sole significant predictor of reduced Marx activity level was the presence of a grade 4 lesion on the MFC. Lateral meniscus repairs

  4. Platelet-rich plasma gel promotes regeneration of articular cartilage in knees of sheeps.

    Science.gov (United States)

    Carneiro, Márcio de Oliveira; Barbieri, Cláudio Henrique; Barbieri Neto, José

    2013-03-01

    To assess the regeneration of osteochondral defects in the joint cartilage of the knee induced by autologous platelet-rich plasma (PRP). Osteochondral defects produced in the trochlear groove of both knees of ten sheep; defects of the right knees were filled with autologous PRP and the left knees were left unfilled. Macroscopic and microscopic evaluation was carried out 12 week later. The results were evaluated by the total score of both macroscopic and microscopic evaluations comparing the two sides through the Wilcoxon paired test. Macroscopic appearance was not uniform among animals, nor was it different between the right and left knees (p=0.3125), and in no case the regenerated tissue was equal to the normal surrounding cartilage. At histological examination, apparently normal cartilage was not detected in any knee, but a poorly differentiated cartilage was present in 7 right knees, compared to 3 left knees. Fibrocartilaginous tissue was present in most of the remaining knees, with a significant difference in the overall score between right and left knees (p=0.0313). The PRP as used in this study has reparative properties of the joint cartilage of sheep knees, mostly by stimulating the formation of a fibrocartilaginous tissue. Laboratory investigation.

  5. Automating measurement of subtle changes in articular cartilage from MRI of the knee by combining 3D image registration and segmentation

    Science.gov (United States)

    Lynch, John A.; Zaim, Souhil; Zhao, Jenny; Peterfy, Charles G.; Genant, Harry K.

    2001-07-01

    In osteoarthritis, articular cartilage loses integrity and becomes thinned. This usually occurs at sites which bear weight during normal use. Measurement of such loss from MRI scans, requires precise and reproducible techniques, which can overcome the difficulties of patient repositioning within the scanner. In this study, we combine a previously described technique for segmentation of cartilage from MRI of the knee, with a technique for 3D image registration that matches localized regions of interest at followup and baseline. Two patients, who had recently undergone meniscal surgery, and developed lesions during the 12 month followup period were examined. Image registration matched regions of interest (ROI) between baseline and followup, and changes within the cartilage lesions were estimate to be about a 16% reduction in cartilage volume within each ROI. This was more than 5 times the reproducibility of the measurement, but only represented a change of between 1 and 2% in total femoral cartilage volume. Changes in total cartilage volume may be insensitive for quantifying changes in cartilage morphology. A combined used of automated image segmentation, with 3D image registration could be a useful tool for the precise and sensitive measurement of localized changes in cartilage from MRI of the knee.

  6. 3D Dynamic Culture of Rabbit Articular Chondrocytes Encapsulated in Alginate Gel Beads Using Spinner Flasks for Cartilage Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Feiyue Xu

    2014-01-01

    Full Text Available Cell-based therapy using chondrocytes for cartilage repair suffers from chondrocyte dedifferentiation. In the present study, the effects of an integrated three-dimensional and dynamic culture on rabbit articular chondrocytes were investigated. Cells (passages 1 and 4 were encapsulated in alginate gel beads and cultured in spinner flasks in chondrogenic and chondrocyte growth media. Subcutaneous implantation of the cell-laden beads was performed to evaluate the ectopic chondrogenesis. It was found that cells remained viable after 35 days in the three-dimensional dynamic culture. Passage 1 cells demonstrated a proliferative growth in both media. Passage 4 cells showed a gradual reduction in DNA content in growth medium, which was attenuated in chondrogenic medium. Deposition of glycosaminoglycans (GAG was found in all cultures. While passage 1 cells generally produced higher amounts of GAG than passage 4 cells, GAG/DNA became similar on day 35 for both cells in growth media. Interestingly, GAG/DNA in growth medium was greater than that in chondrogenic medium for both cells. Based on GAG quantification and gene expression analysis, encapsulated passage 1 cells cultured in growth medium displayed the best ectopic chondrogenesis. Taken together, the three-dimensional and dynamic culture for chondrocytes holds great potential in cartilage regeneration.

  7. Changes in chondrocyte gene expression following in vitro impaction of porcine articular cartilage in an impact injury model.

    Science.gov (United States)

    Ashwell, Melissa S; Gonda, Michael G; Gray, Kent; Maltecca, Christian; O'Nan, Audrey T; Cassady, Joseph P; Mente, Peter L

    2013-03-01

    Our objective was to monitor chondrocyte gene expression at 0, 3, 7, and 14 days following in vitro impaction to the articular surface of porcine patellae. Patellar facets were either axially impacted with a cylindrical impactor (25 mm/s loading rate) to a load level of 2,000 N or not impacted to serve as controls. After being placed in organ culture for 0, 3, 7, or 14 days, total RNA was isolated from full thickness cartilage slices and gene expression measured for 17 genes by quantitative real-time RT-PCR. Targeted genes included those encoding proteins involved with biological stress, inflammation, or anabolism and catabolism of cartilage extracellular matrix. Some gene expression changes were detected on the day of impaction, but most significant changes occurred at 14 days in culture. At 14 days in culture, 10 of the 17 genes were differentially expressed with col1a1 most significantly up-regulated in the impacted samples, suggesting impacted chondrocytes may have reverted to a fibroblast-like phenotype. Copyright © 2012 Orthopaedic Research Society.

  8. Histological and biochemical evaluation of perichondrial transplants in human articular cartilage defects

    NARCIS (Netherlands)

    Bouwmeester, P; Kuijer, R; Terwindt-Rouwenhorst, E; van der Linden, Ton; Bulstra, K

    1999-01-01

    From 1986 to 1992, 88 patients with articular defects in the knee were treated with a perichondrial arthroplasty. In this study, we report on the results for 22 biopsies of grafted tissue with a mean follow-up of 21 months. Biopsies were obtained at routine arthroscopy after approximately 1 year or

  9. Biofabrication of implants for articular joint repair : Cartilage regeneration in reinforced gelatin-based hydrogels

    NARCIS (Netherlands)

    Visser, J.

    2015-01-01

    Implants were biofabricated for the repair of chondral and osteochondral articular joint defects. The implants were based on gelatin methacrylamide (GelMA) hydrogels combined with printed fibers from polycaprolactone (PCL) for mechanical reinforcement. In Part I of the thesis, biological

  10. Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway.

    Science.gov (United States)

    Qin, Na; Wei, Liwei; Li, Wuyin; Yang, Wei; Cai, Litao; Qian, Zhuang; Wu, Shufang

    2017-07-01

    Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway

    Directory of Open Access Journals (Sweden)

    Na Qin

    2017-07-01

    Full Text Available Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway.

  12. The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants

    Energy Technology Data Exchange (ETDEWEB)

    Kawabe, N.; Yoshinao, M. (Department of Orthopaedics, Shimane Medical School, Izumo (Japan))

    1991-07-01

    Growth plate cartilage cultivated in vitro was attached with a fibrin clot to a full-thickness articular cartilage defect on knee joints in allogeneic New Zealand rabbits. The healing of the defects was assessed by gross examination, light microscopy, and immunologic analysis for 24 weeks. Immunologic assessment of cell-mediated immunity, cytotoxicity of a humoral antibody by a 51 chromium release assay, and immunofluorescence studies were carried out. During the first two weeks following grafting, healing was excellent in 11 of the 17 defects. From three to 24 weeks, 11 of 42 defects examined had good results. Host lymphocytes had accumulated around the allograft at two to 12 weeks. Most of the implanted cartilage grown in vitro died and was replaced by fibrous tissue. The immunologic studies suggested that the implanted cartilage began to degenerate two to three weeks after implantation partially because of a humoral immune response but more importantly because of cell-mediated cytotoxicity.

  13. Transforming growth factor β-induced superficial zone protein accumulation in the surface zone of articular cartilage is dependent on the cytoskeleton.

    Science.gov (United States)

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2014-03-01

    The phenotype of articular chondrocytes is dependent on the cytoskeleton, specifically the actin microfilament architecture. Articular chondrocytes in monolayer culture undergo dedifferentiation and assume a fibroblastic phenotype. This process can be reversed by altering the actin cytoskeleton by treatment with cytochalasin. Whereas dedifferentiation has been studied on chondrocytes isolated from the whole cartilage, the effects of cytoskeletal alteration on specific zones of cells such as superficial zone chondrocytes are not known. Chondrocytes from the superficial zone secrete superficial zone protein (SZP), a lubricating proteoglycan that reduces the coefficient of friction of articular cartilage. A better understanding of this phenomenon may be useful in elucidating chondrocyte dedifferentiation in monolayer and accumulation of the cartilage lubricant SZP, with an eye toward tissue engineering functional articular cartilage. In this investigation, the effects of cytoskeletal modulation on the ability of superficial zone chondrocytes to secrete SZP were examined. Primary superficial zone chondrocytes were cultured in monolayer and treated with a combination of cytoskeleton modifying reagents and transforming growth factor β (TGFβ) 1, a critical regulator of SZP production. Whereas cytochalasin D maintains the articular chondrocyte phenotype, the hallmark of the superficial zone chondrocyte, SZP, was inhibited in the presence of TGFβ1. A decrease in TGFβ1-induced SZP accumulation was also observed when the microtubule cytoskeleton was modified using paclitaxel. These effects of actin and microtubule alteration were confirmed through the application of jasplakinolide and colchicine, respectively. As Rho GTPases regulate actin organization and microtubule polymerization, we hypothesized that the cytoskeleton is critical for TGFβ-induced SZP accumulation. TGFβ-mediated SZP accumulation was inhibited by small molecule inhibitors ML141 (Cdc42), NSC23766 (Rac1

  14. Influence of Knee Immobilization on Chondrocyte Apoptosis and Histological Features of the Anterior Cruciate Ligament Insertion and Articular Cartilage in Rabbits.

    Science.gov (United States)

    Mutsuzaki, Hirotaka; Nakajima, Hiromi; Wadano, Yasuyoshi; Furuhata, Syogo; Sakane, Masataka

    2017-01-26

    This study examined the influence of immobilization on chondrocyte apoptosis and histological features of the anterior cruciate ligament (ACL) insertion and knee articular cartilage in rabbits. Forty-eight male Japanese white rabbits were assigned to an immobilization (n = 24) or sham (n = 24) group. Rabbits in the immobilization group underwent complete unilateral surgical knee immobilization and rabbits in the sham group underwent a sham surgery. The average thickness of the glycosaminoglycan (GAG) stained red area by safranin O staining, the chondrocyte apoptosis rate and the chondrocyte proliferation rate in the cartilage layer in the ACL insertion and the articular cartilage of the medial tibial condyle were measured at one, two, four and eight weeks in six animals from each group. In the ACL insertion, the chondrocyte apoptosis rate was higher in the immobilization group than in the sham group at two and eight weeks after surgery (p immobilization group. The GAG layer was thinner in the immobilization group than in the sham group at two, four and eight weeks after surgery (p immobilization group was higher than in the sham group at four and eight weeks after surgery (p immobilization group than that in the sham group at four and eight weeks after surgery (p immobilization significantly increased chondrocyte apoptosis at two and eight weeks after surgery in the ACL insertion and at four and eight weeks after surgery in the articular cartilage of the medial tibial condyle, and decreased GAG layer thickness from two to eight weeks after surgery in the ACL insertion and from four to eight weeks after surgery in the articular cartilage.

  15. The Effect of Aging and Mechanical Loading on the Metabolism of Articular Cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Adam El Mongy; Kjaer, Michael; Heinemeier, Katja Maria

    2017-01-01

    collagen network damage and proteoglycan loss, leading to irreversible cartilage destruction because of lack of regenerative capacity. Catabolic pathways involve inflammation and the transcription factor nuclear factor-κB. Thus, age seems to be a predisposing factor for OA, with mechanical overload being...

  16. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration

    NARCIS (Netherlands)

    Mouser, Vivian H M; Levato, Riccardo; Bonassar, Lawrence J; D'Lima, Darryl D; Grande, Daniel A; Klein, Travis J; Saris, Daniel B F; Zenobi-Wong, Marcy; Gawlitta, Debby; Malda, Jos

    2017-01-01

    Three-dimensional (3D) bioprinting techniques can be used for the fabrication of personalized, regenerative constructs for tissue repair. The current article provides insight into the potential and opportunities of 3D bioprinting for the fabrication of cartilage regenerative constructs. Although 3D

  17. Collagene order of articular cartilage by clinical magnetic resonance images and its age dependency

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, P.; Gruender, W. [Inst. of Medical Physics and Biophysics, Univ. of Leipzig (Germany)

    2005-07-01

    The present papers describes a novel method to obtain information on the degree of order of the collagen network of the knee meniscal cartilage by means of a single clinical MRI. Images were obtained from 34 healthy volunteers aged between 6 and 76 years as well as from one patient with clinically-diagnosed arthrosis at the age of 32 and 37 years. A siemens vision (1.5 T) MRT with TR = 750 ms, TE = 50 ms, FoV = 160 mm, and Matrix 512 x 512 was used for this purpose. The MR signal intensities of the cartilage were read out along slices with constant height above the subchondral bone and plotted versus the actual angle to the external magnetic field. The obtained intensity curves were fitted by a model distribution, and the degree of order of the collagen fibers was calculated. For the knee meniscal cartilage, there was an age-dependency of the degree of order and a significant deviation of the volunteer with arthrosis from the normal curve. The results are discussed in view of the arcade model and of a possible use of non-invasive clinical MRT for the detection of early arthrotic changes of cartilage. (orig.)

  18. The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee joint.

    Science.gov (United States)

    Valiyaveettil, Manojkumar; Mort, John S; McDevitt, Cahir A

    2005-01-01

    The concentration, spatial distribution, and gene expression of aggrecan in meniscus, articular cartilage, and the anterior and posterior cruciate ligaments (ACL and PCL) was determined in the knee joints of five mature dogs. An anti-serum against peptide sequences specific to the G1 domain of aggrecan was employed in competitive-inhibition ELISA of guanidine HCl extracts and immunofluorescence microscopy. Gene expression was determined by Taqman real-time PCR. The concentration of aggrecan in articular cartilage (240.1 +/- 32 nMol/g dry weight) was higher than that in meniscus (medial meniscus: 33.4 +/- 4.3 nMol/g) and ligaments (ACL: 6.8 +/- 0.9 nMol/g). Aggrecan was more concentrated in the inner than the outer zone of the meniscus. Aggrecan in meniscus showed an organized, spatial network, in contrast to its diffuse distribution in articular cartilage. Thus, differences in the concentration, gene expression, and spatial distribution of aggrecan constitute another molecular distinction between hyaline cartilage and fibrocartilage of the knee.

  19. Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs for MRI assessment of the cartilage barrier in a large animal model.

    Directory of Open Access Journals (Sweden)

    Raphael Labens

    Full Text Available Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI. Conditioned (following matrix depletion and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function

  20. Effect of Acupotomy on FAK-PI3K Signaling Pathways in KOA Rabbit Articular Cartilages

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    Shi-Ning Ma

    2017-01-01

    Full Text Available Objective. By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. Method. 49 male New Zealand rabbits, randomly divided into normal group (Z, model group (M, model-inhibitors (MP, needle-knife group (D, needle-knife inhibitors group (DP, electroacupuncture group (E, and electroacupuncture inhibitors (EP. RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. Results. Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05, while the protein and mRNA expression of Aggrecan reduced (P < 0.05. Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05. Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05; after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05. Conclusion. Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.

  1. Routine clinical knee MR reports: comparison of diagnostic performance at 1.5 T and 3.0 T for assessment of the articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Mandell, Jacob C.; Rhodes, Jeffrey A.; Shah, Nehal; Gaviola, Glenn C.; Smith, Stacy E. [Brigham and Women' s Hospital, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); Gomoll, Andreas H. [Brigham and Women' s Hospital, Cartilage Repair Center, Department of Orthopedic Surgery, Boston, MA (United States)

    2017-11-15

    Accurate assessment of knee articular cartilage is clinically important. Although 3.0 Tesla (T) MRI is reported to offer improved diagnostic performance, literature regarding the clinical impact of MRI field strength is lacking. The purpose of this study is to compare the diagnostic performance of clinical MRI reports for assessment of cartilage at 1.5 and 3.0 T in comparison to arthroscopy. This IRB-approved retrospective study consisted of 300 consecutive knees in 297 patients who had routine clinical MRI and arthroscopy. Descriptions of cartilage from MRI reports of 165 knees at 1.5 T and 135 at 3.0 T were compared with arthroscopy. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade of the arthroscopic grading were calculated for each articular surface at 1.5 and 3.0 T. Agreement between MRI and arthroscopy was calculated with the weighted-kappa statistic. Significance testing was performed utilizing the z-test after bootstrapping to obtain the standard error. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade were 61.4%, 82.7%, 62.2%, and 77.5% at 1.5 T and 61.8%, 80.6%, 59.5%, and 75.6% at 3.0 T, respectively. The weighted kappa statistic was 0.56 at 1.5 T and 0.55 at 3.0 T. There was no statistically significant difference in any of these parameters between 1.5 and 3.0 T. Factors potentially contributing to the lack of diagnostic advantage of 3.0 T MRI are discussed. (orig.)

  2. Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

    Directory of Open Access Journals (Sweden)

    Sondergaard Bodil-Cecilie

    2009-12-01

    Full Text Available Abstract Background Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. Findings Bovine cartilage explants were cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM and tumor necrosis factor alpha (TNFα. In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo-epitope specific immunoassays; (1 sandwich 342FFGVG-G2 ELISA, (2 competition NITEGE373ELISA (3 sandwich G1-NITEGE373 ELISA (4 competition 374ARGSV ELISA, and (5 sandwich 374ARGSV-G2 ELISA all detecting aggrecan fragments, and (6 sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen. We found that (1 aggrecanase-derived aggrecan fragments are released in the early (day 2-7 and mid phase (day 9-14 into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2 the release of NITEGE373 neo-epitopes are delayed compared to the corresponding 374ARGSV fragments, (3 the MMP inhibitor GM6001 did not reduce the release of aggrecanase-derived fragment, but induced a further delay in the release of these fragments, and finally (4 the MMP-derived aggrecan and type II collagen fragments were released in the late phase (day 16-21 only. Conclusion Our data support the model, that aggrecanases and MMPs act independently in the processing of the aggrecan molecules, and furthermore that suppression of MMP-activity had little if

  3. Application of tissue engineering technology for formation of human articular cartilage in perfusion bioreactor

    Directory of Open Access Journals (Sweden)

    V. I. Sevastianov

    2017-01-01

    Full Text Available Formation of tissue-engineered construct was performed in a specially developed bioreactor. At first, a cellengineered construct of human cartilage tissue consisting of biopolymer microstructured collagen-containing hydrogel, mesenchymal stromal cells of human adipose tissue (hADMSCs and induction chondrogenic culture medium was prepared and placed in a perfusion bioreactor. As a result, on the 16th day of the study hADMSCs obtain a flattened shape typical for chondroblasts and demonstrate high proliferative activity with the formation of their own extracellular matrix. Histological analysis of the cultured system indicates the beginning of the formation of a tissue-engineered construct of human cartilage tissue.

  4. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

    Science.gov (United States)

    Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

    2006-11-01

    In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

  5. Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain.

    Directory of Open Access Journals (Sweden)

    Catherine A Leonard

    Full Text Available Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ "super-healer" mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant.The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ "super-healer" mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints.Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair.The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow.

  6. Preclinical investigations of articular cartilage ablation with femtosecond and pulsed infrared lasers as an alternative to microfracture surgery

    Science.gov (United States)

    Su, Erica; Sun, Hui; Juhasz, Tibor; Wong, Brian J. F.

    2014-01-01

    Abstract. Microfracture surgery is a bone marrow stimulation technique for treating cartilage defects and injuries in the knee. Current methods rely on surgical skill and instrumentation. This study investigates the potential use of laser technology as an alternate means to create the microfracture holes. Lasers investigated in this study include an erbium:YAG laser (λ=2.94  μm), titanium:sapphire femtosecond laser system (λ=1700  nm), and Nd:glass femtosecond laser (λ=1053  nm). Bovine samples were ablated at fluences of 8 to 18  J/cm2 with the erbium:YAG laser, at a power of 300±15  mW with the titanium:sapphire femtosecond system, and at an energy of 3  μJ/pulse with the Nd:glass laser. Samples were digitally photographed and histological sections were taken for analysis. The erbium:YAG laser is capable of fast and efficient ablation; specimen treated with fluences of 12 and 18  J/cm2 experienced significant amounts of bone removal and minimal carbonization with saline hydration. The femtosecond laser systems successfully removed cartilage but not clinically significant amounts of bone. Precise tissue removal was possible but not to substantial depths due to limitations of the systems. With additional studies and development, the use of femtosecond laser systems to ablate bone may be achieved at clinically valuable ablation rates. PMID:25200394

  7. Protection of the Medial Femoral Condyle Articular Cartilage During Drilling of the Femoral Tunnel Through the Accessory Medial Portal in Anatomic Anterior Cruciate Ligament Reconstruction

    OpenAIRE

    Abdelkafy, Ashraf

    2012-01-01

    Accurate positioning of the femoral tunnel in the native femoral anterior cruciate ligament (ACL) footprint requires drilling through an accessory medial portal (AMP). The AMP is located far medial and at a low level. Despite the benefits of drilling through the AMP, it is possible that the drill bit head will injure the articular cartilage of the medial femoral condyle as it slides along the guide pin to the femoral insertion of the ACL. Because more surgeons are now performing anatomic ACL ...

  8. Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.

    Science.gov (United States)

    Shimada, Hirofumi; Sakakima, Harutoshi; Tsuchimochi, Kaneyuki; Matsuda, Fumiyo; Komiya, Setsuro; Goldring, Mary B; Ijiri, Kosei

    2011-04-15

    Growth arrest and DNA damage-inducible protein 45β (GADD45β) is expressed in normal and early osteoarthritic articular cartilage. We recently reported that GADD45β enhances CCAAT/enhancer binding protein β (C/EBPβ) activation in vitro. This study was undertaken in order to determine whether GADD45β is expressed with C/EBPβ in aging articular cartilage. We also investigated whether the synergistic expression of GADD45β and C/EBPβ may be involved in the mechanism of chondrocyte senescence. Senescence-accelerated mice (SAMP1) were used as a model of aging. GADD45β, C/EBPβ, and p21 were analyzed by immunohistochemistry. A luciferase reporter assay using ATDC5 cells was performed in order to examine p21 as a target gene of the GADD45β/C/EBPβ cascade. GADD45β exhibited increased expression in the aging articular cartilage of SAMP1 mice compared to that in control mice. The co-localization of GADD45β and C/EBPβ was confirmed by double immunostaining. The synergistic mechanisms of GADD45β and C/EBPβ on the gene regulation of p21, a molecule related to cellular senescence, were verified by a p21-luciferase reporter assay. Co-expression of C/EBPβ and p21 was confirmed. These observations suggest that the synergism between GADD45β and C/EBPβ may play an important role in cellular senescence in the aging articular cartilage. Crown Copyright © 2011. Published by Elsevier GmbH. All rights reserved.

  9. Articular cartilage destruction in experimental inflammatory arthritis: Insulin-like growth factor-1 regulation of proteoglycan metabolism in chondrocytes

    NARCIS (Netherlands)

    Verschure, P. J.; van Noorden, C. J.; van Marle, J.; van den Berg, W. B.

    1996-01-01

    Rheumatoid arthritis, a disease of unknown aetiology, is characterized by joint inflammation and, in its later stages, cartilage destruction. Inflammatory mediators may exert not only suppression of matrix synthesis but also cartilage degradation, which eventually leads to severe cartilage

  10. Sliding enhances fluid and solute transport into buried articular cartilage contacts.

    Science.gov (United States)

    Graham, B T; Moore, A C; Burris, D L; Price, C

    2017-12-01

    Solutes and interstitial water are naturally transported from cartilage by load-induced interstitial fluid pressures. Fluid and solute recovery during joint articulation have been primarily attributed to passive diffusion and mechanical 'pumping' from dynamic loading. This paper tests if the sliding action of articulation is a significant and independent driver of fluid and solute transport in cartilage. The large osteochondral samples utilized in the present study preserve the convergent wedges necessary for physiological hydrodynamics. Following static load-induced fluid exudation and prior to sliding, a fluorescent solute (AlexaFluor 633) was added to the lubricant bath. In situ confocal microscopy was used to quantify the transport of solute from the bath into the buried stationary contact area (SCA) during sliding. Following static exudation, significant reductions in friction and strain during sliding at 60 mm/s were accompanied by significant solute transport into the inaccessible center of the buried contact; no such transport was detected for the 0- or 1 mm/s sliding conditions. The results suggest that external hydrodynamic pressures from sliding induced advective flows that carried solutes from the bath toward the center of contact. These results provide the first direct evidence that the action of sliding is a significant contributor to fluid and solute recovery by cartilage. Furthermore, they indicate that the sliding-induced transport of solutes into the buried interface was orders of magnitude greater than that attributable to diffusion alone, a result with critical implications for disease prevention and tissue engineering. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Granulocyte macrophage - colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture.

    Science.gov (United States)

    Truong, M-D; Choi, B H; Kim, Y J; Kim, M S; Min, B-H

    2017-08-01

    To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF + MFX. GM-CSF was administrated intravenously (IV) at 10 μg/kg body weight 20 min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by near-Infrared (NIR) fluorescence imaging and enzyme-linked immune sorbent assay. In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF + MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10 min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects. Copyright © 2017. Published by Elsevier Ltd.

  12. Efeitos dos glicosaminoglicanos e sulfato de condroitina A sobre a cartilagem articular normal e com doença articular degenerativa em cães Glycosaminoglycans and chondroitin sulphate "A" effects on normal and osteoarthritic articular cartilage in dogs

    Directory of Open Access Journals (Sweden)

    N.T. Vieira

    2010-10-01

    Full Text Available Avaliaram-se os efeitos dos precursores dos glicosaminoglicanos (GAG e do sulfato de condroitina A (SC sobre a histomorfometria da cartilagem articular normal ou de cartilagem de cães com doença articular degenerativa (DAD experimental. Os grupos experimentais constituíram-se de animais com articulação direita normal, que não foi submetida a procedimento cirúrgico, e com articulação esquerda osteoartrótica e que foi submetida à intervenção cirúrgica. Os grupos foram subdivididos em animais com articulação não tratada e tratada, portanto: normais (N (n=5, NGAG (n=5 e NSC (n=4; e osteoartróticos (O (n=5, OGAG (n=5 e OSC (n=4. Secções de cartilagens do fêmur, da tíbia e da patela foram utilizadas neste estudo. Nos normais (N, NGAG e NSC, não se encontraram lesões que caracterizassem a DAD, embora tenha havido diminuição na celularidade nos de NGAG e NSC, em relação a N. Foram observadas alterações em graus variáveis entre os grupos osteoartróticos. Houve redução acentuada dos condrócitos no grupo O em comparação aos normais enquanto os grupos osteoartróticos tratados apresentaram celularidade semelhante aos normais tratados. Estes resultados foram confirmados pela análise do índice de proporção (IP, que se mostrou elevado em O, indicando menor síntese de proteoglicanos. Não houve diferença significativa entre os IPs dos grupos osteoartróticos tratados (OGAG, OSC apesar do comportamento distinto do OSC ao assemelhar-se aos grupos N e NSC. Estes resultados sugeriram que o SC agiu na cartilagem osteoartrótica de maneira mais eficaz, reduzindo a perda de proteoglicanos e estimulando a viabilidade celular e a atividade metabólica.The effects of precursors of glycosaminoglycans (GAG and chondroitin sulphate A (CS on the histomorphometry of normal articular cartilage and with experimental degenerative joint disease (DJD in dogs were evaluated. The groups were constituted as follows: normal joints were not

  13. Hyaluronan Does Not Affect Bupivacaine’s Inhibitory Action on Voltage-Gated Potassium Channel Activities in Bovine Articular Chondrocytes

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    William Hester

    2012-01-01

    Full Text Available Objectives. The objective of this paper is to determine if hyaluronan affects bupivacaine’s anesthetic function. Methods. Whole cell patch clamp recordings were performed on bovine articular chondrocytes cultured in 60 mm dishes. The chondrocytes were treated with phosphate-buffered saline (control group, 7.5 mg/mL hyaluronan (Orthovisc, 0.25% bupivacaine, or a mixture of 7.5 mg/mL hyaluronan and 0.25% bupivacaine. Outward currents were elicited by step depolarization from −90 mV to 150 mV with 5 mV increments and holding for 200 ms. Results. The amplitude of outward currents elicited at 150 mV was 607.1±135.4 pA (mean ± standard error in the chondrocytes treated with phosphate buffered saline, 550.0±194.9 pA in the chondrocytes treated with hyaluronan, 18.4±8.3 pA in the chondrocytes treated with bupivacaine, and 12.8±2.6 pA in the chondrocytes treated with a mixture of hyaluronan and bupivacaine. Conclusion. Hyaluronan does not affect bupivacaine’s inhibitory action on the potassium channel activities in bovine articular chondrocytes. This finding suggests that intra-articular injection of a mixture of hyaluronan and bupivacaine may not affect the anesthetic effects of bupivacaine.

  14. Effects of Medium and Temperature on Cellular Responses in the Superficial Zone of Hypo-Osmotically Challenged Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Mikko Lammi

    2012-08-01

    Full Text Available Osmotic loading of articular cartilage has been used to study cell-tissue interactions and mechanisms in chondrocyte volume regulation in situ. Since cell volume changes are likely to affect cell’s mechanotransduction, it is important to understand how environmental factors, such as composition of the immersion medium and temperature affect cell volume changes in situ in osmotically challenged articular cartilage. In this study, chondrocytes were imaged in situ with a confocal laser scanning microscope (CLSM through cartilage surface before and 3 min and 120 min after a hypo-osmotic challenge. Samples were measured either in phosphate buffered saline (PBS, without glucose and Ca2+ or in Dulbecco’s modified Eagle’s medium (DMEM, with glucose and Ca2+, and at 21 °C or at 37 °C. In all groups, cell volumes increased shortly after the hypotonic challenge and then recovered back to the original volumes. At both observation time points, cell volume changes as a result of the osmotic challenge were similar in PBS and DMEM in both temperatures. Our results indicate that the initial chondrocyte swelling and volume recovery as a result of the hypo-osmotic challenge of cartilage are not dependent on commonly used immersion media or temperature.

  15. An in vitro comparative study of T2 and T2* mappings of human articular cartilage at 3-Tesla MRI using histology as the standard of reference

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    Kim, Taehee; Park, Sunghoon [Ajou University School of Medicine, Department of Radiology, Suwon (Korea, Republic of); Ajou University Medical Center, Musculoskeletal Imaging Laboratory, Suwon (Korea, Republic of); Min, Byoung-Hyun [Ajou University School of Medicine, Department of Orthopaedic Surgery, Suwon (Korea, Republic of); Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of); Yoon, Seung-Hyun [Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of); Kim, Hakil [INHA University, School of Information and Communication Engineering, Incheon (Korea, Republic of); Lee, Hyun Young [Ajou University Medical Center, Regional Clinical Trial Center, Suwon (Korea, Republic of); Yonsei University College of Medicine, Department of Biostatistics, Seoul (Korea, Republic of); Kwack, Kyu-Sung [Ajou University School of Medicine, Department of Radiology, Suwon (Korea, Republic of); Ajou University Medical Center, Musculoskeletal Imaging Laboratory, Suwon (Korea, Republic of); Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of)

    2014-07-15

    The aim of this study was to evaluate the correlations between T2 value, T2* value, and histological grades of degenerated human articular cartilage. T2 mapping and T2* mapping of nine tibial osteochondral specimens were obtained using a 3-T MRI after total knee arthroplasty. A total of 94 ROIs were analyzed. Histological grades were assessed using the David-Vaudey scale. Spearman's rho correlation analysis and Pearson's correlation analysis were performed. The mean relaxation values in T2 map with different histological grades (0, 1, 2) of the cartilage were 51.9 ± 9.2 ms, 55.8 ± 12.8 ms, and 59.6 ± 10.2 ms, respectively. The mean relaxation values in T2* map with different histological grades (0, 1, 2) of the cartilage were 20.3 ± 10.3 ms, 21.1 ± 12.4 ms, and 15.4 ± 8.5 ms, respectively. Spearman's rho correlation analysis confirmed a positive correlation between T2 value and histological grade (ρ = 0.313, p < 0.05). Pearson's correlation analysis revealed a significant negative correlation between T2 and T2* (r = -0.322, p < 0.05). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, this correlation was not statistically significant in this study (ρ = -0.192, p = 0.129). T2 mapping was correlated with histological degeneration, and it may be a good biomarker for osteoarthritis in human articular cartilage. However, the strength of the correlation was weak (ρ = 0.313). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, the correlation was not statistically significant. Therefore, T2 mapping may be more appropriate for the initial diagnosis of articular cartilage degeneration in the knee joint. Further studies on T2* mapping are needed to confirm its reliability and mechanism in cartilage degeneration. (orig.)

  16. Demonstration of the therapeutic effect of /sup 35/S labelled L-cystine in articular and intervertebral cartilage as well as in skeletal musculature

    Energy Technology Data Exchange (ETDEWEB)

    Schmiegelow, P.; Puschmann, M.; Giese, U.

    1984-01-16

    Clinical experience has obviously shown a positive effect of application of sulfated amino acids on degenerative cartilage diseases. L-Cystin, presumed to be of therapeutic effect, was autoradiographically localized in articular, columnar and intervertebral cartilage as well as in skeletal musculature. In 10 days old NMRI-mice, we had shown a dose-dependent incorporation of the radioactively labelled /sup 35/S-Cystin in hair follicle. These statistically significant differences had been measured by quantitative autoradiographical microscope photometry. The sulfated amino acids are also proven in nail matrix, nail hyponychium as well as in cartilage and skeletal musculature. Besides a localization of radioactively labelled L-Cystin in tissues, presumed as target organs of a therapeutic effect, there is still lacking an experimental proof of efficacy on cell proliferation and functional metabolism e.g. in arthrosis by suitable animal models.

  17. Modulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage.

    Science.gov (United States)

    Thorpe, Stephen D; Nagel, Thomas; Carroll, Simon F; Kelly, Daniel J

    2013-01-01

    Engineering organs and tissues with the spatial composition and organisation of their native equivalents remains a major challenge. One approach to engineer such spatial complexity is to recapitulate the gradients in regulatory signals that during development and maturation are believed to drive spatial changes in stem cell differentiation. Mesenchymal stem cell (MSC) differentiation is known to be influenced by both soluble factors and mechanical cues present in the local microenvironment. The objective of this study was to engineer a cartilaginous tissue with a native zonal composition by modulating both the oxygen tension and mechanical environment thorough the depth of MSC seeded hydrogels. To this end, constructs were radially confined to half their thickness and subjected to dynamic compression (DC). Confinement reduced oxygen levels in the bottom of the construct and with the application of DC, increased strains across the top of the construct. These spatial changes correlated with increased glycosaminoglycan accumulation in the bottom of constructs, increased collagen accumulation in the top of constructs, and a suppression of hypertrophy and calcification throughout the construct. Matrix accumulation increased for higher hydrogel cell seeding densities; with DC further enhancing both glycosaminoglycan accumulation and construct stiffness. The combination of spatial confinement and DC was also found to increase proteoglycan-4 (lubricin) deposition toward the top surface of these tissues. In conclusion, by modulating the environment through the depth of developing constructs, it is possible to suppress MSC endochondral progression and to engineer tissues with zonal gradients mimicking certain aspects of articular cartilage.

  18. scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints.

    Science.gov (United States)

    Watson, R S; Broome, T A; Levings, P P; Rice, B L; Kay, J D; Smith, A D; Gouze, E; Gouze, J-N; Dacanay, E A; Hauswirth, W W; Nickerson, D M; Dark, M J; Colahan, P T; Ghivizzani, S C

    2013-06-01

    With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human and equine synovial fibroblasts in culture, we found that both were only receptive to transduction with AAV1, 2 and 5. For these serotypes, however, transgene expression from the equine cells was consistently at least 10-fold higher. Analyses of AAV surface receptor molecules and intracellular trafficking of vector genomes implicate enhanced viral uptake by the equine cells. Following delivery of 1 × 10(11) vector genomes of serotypes 2, 5 and 8 into the forelimb joints of the horse, all three enabled hIL-1Ra expression at biologically relevant levels and effectively transduced the same cell types, primarily synovial fibroblasts and, to a lesser degree, chondrocytes in articular cartilage. These results provide optimism that AAV vectors can be effectively adapted for gene delivery to large human joints affected by OA.

  19. Anomalous Behavior of Hyaluronan Crosslinking Due to the Presence of Excess Phospholipids in the Articular Cartilage System of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Piotr Bełdowski

    2017-12-01

    Full Text Available Lubrication of articular cartilage is a complex multiscale phenomenon in synovial joint organ systems. In these systems, synovial fluid properties result from synergistic interactions between a variety of molecular constituent. Two molecular classes in particular are of importance in understanding lubrication mechanisms: hyaluronic acid and phospholipids. The purpose of this study is to evaluate interactions between hyaluronic acid and phospholipids at various functionality levels during normal and pathological synovial fluid conditions. Molecular dynamic simulations of hyaluronic acid and phospholipids complexes were performed with the concentration of hyaluronic acid set at a constant value for two organizational forms, extended (normal and coiled (pathologic. The results demonstrated that phospholipids affect the crosslinking mechanisms of hyaluronic acid significantly and the influence is higher during pathological conditions. During normal conditions, hyaluronic acid and phospholipid interactions seem to have no competing mechanism to that of the interaction between hyaluronic acid to hyaluronic acid. On the other hand, the structures formed under pathologic conditions were highly affected by phospholipid concentration.

  20. Modulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage.

    Directory of Open Access Journals (Sweden)

    Stephen D Thorpe

    Full Text Available Engineering organs and tissues with the spatial composition and organisation of their native equivalents remains a major challenge. One approach to engineer such spatial complexity is to recapitulate the gradients in regulatory signals that during development and maturation are believed to drive spatial changes in stem cell differentiation. Mesenchymal stem cell (MSC differentiation is known to be influenced by both soluble factors and mechanical cues present in the local microenvironment. The objective of this study was to engineer a cartilaginous tissue with a native zonal composition by modulating both the oxygen tension and mechanical environment thorough the depth of MSC seeded hydrogels. To this end, constructs were radially confined to half their thickness and subjected to dynamic compression (DC. Confinement reduced oxygen levels in the bottom of the construct and with the application of DC, increased strains across the top of the construct. These spatial changes correlated with increased glycosaminoglycan accumulation in the bottom of constructs, increased collagen accumulation in the top of constructs, and a suppression of hypertrophy and calcification throughout the construct. Matrix accumulation increased for higher hydrogel cell seeding densities; with DC further enhancing both glycosaminoglycan accumulation and construct stiffness. The combination of spatial confinement and DC was also found to increase proteoglycan-4 (lubricin deposition toward the top surface of these tissues. In conclusion, by modulating the environment through the depth of developing constructs, it is possible to suppress MSC endochondral progression and to engineer tissues with zonal gradients mimicking certain aspects of articular cartilage.

  1. Reduction of Environmental Temperature Mitigates Local Anesthetic Cytotoxicity in Bovine Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Tarik Onur, Alexis Dang

    2014-09-01

    Full Text Available The purpose of this study was to assess whether reducing environmental temperature will lead to increased chondrocyte viability following injury from a single-dose of local anesthetic treatment. Bovine articular chondrocytes from weight bearing portions of femoral condyles were harvested and cultured. 96-well plates were seeded with 15,000 chondrocytes per well. Chondrocytes were treated with one of the following conditions: ITS Media, 1x PBS, 2% lidocaine, 0.5% bupivacaine, or 0.5% ropivacaine. Each plate was then incubated at 37°C, 23°C, or 4°C for one hour and then returned to media at 37°C. Chondrocyte viability was assessed 24 hours after treatment. Chondrocyte viability is presented as a ratio of the fluorescence of the treatment group over the average of the media group at that temperature (ratio ± SEM. At 37°C, lidocaine (0.35 ± 0.04 and bupivacaine (0.30 ± 0.05 treated chondrocytes show low cell viability when compared to the media (1.00 ± 0.03 control group (p < 0.001. Lidocaine treated chondrocytes were significantly more viable at 23°C (0.84 ± 0.08 and 4°C (0.86±0.085 than at 37°C (p < 0.001. Bupivacaine treated chondrocytes were significantly more viable at 4°C (0.660 ± 0.073 than at 37°C or 23°C (0.330 ± 0.069 (p < 0.001 and p = 0.002 respectively. Reducing the temperature from 37°C to 23°C during treatment with lidocaine increases chondrocyte viability following injury. Chondrocytes treated with bupivacaine can be rescued by reducing the temperature to 4°C.

  2. Return to Sport After Articular Cartilage Repair in Athletes' Knees: A Systematic Review.

    Science.gov (United States)

    Campbell, Andrew B; Pineda, Miguel; Harris, Joshua D; Flanigan, David C

    2016-04-01

    To perform a systematic review of cartilage repair in athletes' knees to (1) determine which (if any) of the most commonly implemented surgical techniques help athletes return to competition, (2) identify which patient- or defect-specific characteristics significantly affect return to sport, and (3) evaluate the methodologic quality of available literature. A systematic review of multiple databases was performed. Return to preinjury level of sport was defined as the ability to play in the same or greater level (i.e., league or division) of competition after surgery. Study methodologic quality for all studies analyzed in this review was evaluated with the Coleman Methodology Score. Systematic review of 1,278 abstracts identified 20 level I-IV studies for inclusion but only 1 randomized controlled trial. Twenty studies (1,117 subjects) were included. Subjects (n = 970) underwent 1 of 4 surgeries (microfracture [n = 529], autologous chondrocyte implantation [ACI, n = 259], osteochondral autograft [n = 139], or osteochondral allograft [n = 43]), and 147 were control patients. The rate of return to sports was greatest after osteochondral autograft transplantation (89%) followed by osteochondral allograft, ACI, and microfracture (88%, 84%, and 75%, respectively). Osteochondral autograft transplantation and ACI had statistically significantly greater rates of return to sports compared with microfracture (P sports participation after microfracture, ACI, osteochondral autograft, or osteochondral allograft, but microfracture patients were least likely to return to sports. The athletes who had a better prognosis after surgery were younger, had a shorter preoperative duration of symptoms, underwent no previous surgical interventions, participated in a more rigorous rehabilitation protocol, and had smaller cartilage defects. Level IV, systematic review of Level I-IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights

  3. Small-angle neutron scattering studies from solutions of bovine nasal cartilage proteoglycan

    Science.gov (United States)

    Patel, A.; Stivala, S. S.; Damle, S. P.; Gregory, J. D.; Bunick, G. J.; Uberbacher, E. C.

    1986-02-01

    Small-angle neutron scattering, SANS, of the proteoglycan subunit of bovine nasal cartilage in 0.15 N LiC1 at 25°C yielded the radius of gyration, R g, radius of gyration of the cross-section, R q, persistence length, a *, and the molecular weight, M. The following values were obtained: M = 3.9 × 10 6, R g = 745 Å, R q = 34.6 Å and a * = 35.2 Å. These values compare favorably with those that were obtained from small angle X-ray scattering, SAXS, of a similar extract. The scattering curve of the proteoglycan subunit in D 2O showed a characteristic broad peak in the specified angular range similar to that observed from SAXS, thus confirming the polyelectrolyte nature of the proteoglycan.

  4. Articular cartilage status 2 years after arthroscopic ACL reconstruction in patients with or without concomitant meniscal surgery: evaluation with 3.0T MR imaging.

    Science.gov (United States)

    Michalitsis, S; Hantes, M; Thriskos, P; Tsezou, A; Malizos, K N; Fezoulidis, I; Vlychou, M

    2017-02-01

    To assess articular cartilage changes in the knee joint as detected on 3.0T MR imaging after 2-year follow-up in patients who underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) with or without concomitant meniscal surgery. A total of twenty-nine patients (mean age 30.3 ± 10 years), who underwent arthroscopic ACLR, received clinical and imaging follow-up at an average of 27.8 ± 4.8 months after surgery. Our patients were divided into two subgroups: eighteen patients with additional meniscal injuries at the time of arthroscopic ACLR who underwent meniscal surgery and eleven patients with intact menisci. The cartilage status of all knees at the time of arthroscopic ACLR was recorded. All patients underwent an MRI scan preoperatively and at follow-up with the same imaging protocol. Cartilage status of all knee compartments was evaluated at the time of follow-up by MR imaging and the ICRS classification. Deterioration of the cartilage status was found at all knee compartments of our study group, with respect to the number of cartilage defects. The cartilage of the lateral femoral condyle (LFC) was most severely affected, followed by patellar and medial femoral condyle (MFC) cartilage. A statistically significant relation was found between surgery of the medial meniscus and the development of new cartilage defects in LFC (p = 0.01) and MFC (p = 0.03) after adjusting for the site of meniscal surgery. The cartilage of LFC and the status of the medial meniscus were also found to be significantly related (p = 0.04). Partial meniscectomy was found to be associated with an increased incidence of new cartilage defects when compared to either meniscal repair or absence of meniscal surgery, although it was not statistically significant. Development of new cartilage lesions was evident after 2-year follow-up in patients with arthroscopic ACLR as detected by MR imaging. There was a multicompartmental pattern of cartilage involvement, and the

  5. Cartilage.

    Science.gov (United States)

    Caplan, Arnold I.

    1984-01-01

    Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

  6. Assessment of T2 Relaxation Times for Normal Canine Knee Articular Cartilage by T2 Mapping Using 1.5-T Magnetic Resonance Imaging.

    Science.gov (United States)

    Matsui, Asami; Shimizu, Miki; Beale, Brian; Takahashi, Fumitaka; Yamaguchi, Sinya

    2017-11-01

    Objectives  This study aims to assess and compare the T2 relaxation times for articular cartilage of normal canine stifle joints in four regions by T2 mapping using a 1.5-T magnetic resonance imaging (MRI). Methods   In vivo prospective study: 20 hindlimbs (left and right) from 10 normal healthy beagle dogs ( n  = 20). The region of interest (ROI) was subdivided into medial and lateral condyles of femoral cartilage (MF and LF, respectively) and medial and lateral condyles of tibial cartilage (MT and LT, respectively). The T2 relaxation times were assessed in regions where the cartilage thickness was greater than 0.5 mm. Results  The median maximum cartilage thickness (mm) of the four ROI were 0.7 (range: 0.9-0.6), 0.6 (range: 0.7-0.5), 0.7 (range: 0.9-0.5) and 0.6 (range: 0.8-0.5) at MF, LF, MT and LT, respectively. The errors in the measurement (%) of the four ROI were 64.3 (range: 50.0-75.0), 75.0 (range: 64.3-90.0), 64.3 (range: 20.0-90.0) and 75.0 (range: 56.3-90.0) at MF, LF, MT and LT, respectively. The median T2 relaxation times (ms) for the articular cartilage of the four ROI were 70.2 (range: 57.9-87.9), 57.5 (range: 46.8-66.9), 65.0 (range: 52.0-92.0) and 57.0 (range: 49.0-66.2) at MF, LF, MT and LT, respectively. The inter-observer correlation coefficient (ICC, 2.1) for the T2 relaxation times of MF was 0.644. Clinical Significance  This study offers useful information on T2 relaxation times for articular cartilage of the stifle joint using a 1.5-T MRI in normal dogs. Schattauer GmbH Stuttgart.

  7. Evaluation of nonbiomedical and biomedical grade alginates for the transplantation of genetically modified articular chondrocytes to cartilage defects in a large animal model in vivo.

    Science.gov (United States)

    Heiligenstein, Susanne; Cucchiarini, Magali; Laschke, Matthias W; Bohle, Rainer M; Kohn, Dieter; Menger, Michael D; Madry, Henning

    2011-04-01

    Genetically modified chondrocytes embedded in alginate improve cartilage repair in experimental models, and alginates are clinically used for articular chondrocyte transplantation. In the present study, we tested the hypothesis that the alginate system allows for sustained transgene expression in cartilage defects in a preclinical large animal model in vivo. Primary cultures of ovine articular chondrocytes were transfected with the Photinus pyralis luc or the Escherichia coli lacZ genes in monolayer culture in vitro using eight different nonviral compounds. Optimally transfected chondrocytes were encapsulated in spheres composed of nonbiomedical or biomedical grade alginates for evaluation of luciferase expression, cell numbers and viabilities in vitro. Transfected chondrocytes encapsulated in spheres comprised of the different alginates were then implanted into osteochondral defects in the knee joints of sheep to examine the profiles of transgene expression in vivo. Ovine articular chondrocytes were efficiently transfected with FuGENE 6. Transgene expression was detectable after encapsulation in the alginates over 21 days in vitro. Transplantation of genetically modified chondrocytes to cartilage defects in vivo resulted in maximal transgene expression on day 1 after transfection, with a decrease by day 21, the longest time point evaluated. Remarkably, the reduction in luciferase activity was less pronounced when biomedical grade alginates were employed, compared to nonbiomedical grade alginates, suggesting that such alginates might be better suited to support elevated transgene expression after transplantation of genetically modified chondrocytes. This approach may be of value to study the effects of potential therapeutic genes upon cartilage repair in a clinically relevant setting. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Effect of dithiocarbamate thiram on Wistar rat growth plate and articular cartilage

    Directory of Open Access Journals (Sweden)

    L. Fialho

    2012-02-01

    Full Text Available Avaliou-se o efeito do tirame, ditiocarbamato largamente utilizado na agricultura como antifúngico e repelente de roedores, na ossificação endocondral de mamíferos, usando, como modelo, ratos Wistar. Não foram observadas lesões na cartilagem articular, nem nas placas de crescimento, o que pode ser atribuído à dose utilizada e à duração do ensaio. A diminuição da altura da placa de crescimento nos animais aos quais foi administrado o tirame parece traduzir o atraso verificado no crescimento em geral, e não um efeito específico na cartilagem, uma vez que as diferentes zonas da placa epifisária mantiveram as proporções dos animais do grupo-controle. Embora não tenham sido verificados, no presente trabalho, os efeitos registrados para outras espécies nos tecidos cartilaginosos, sugere-se a avaliação dos efeitos crónicos do tirame no crescimento e no desenvolvimento dos ossos longos em mamíferos.

  9. Comparison of T2* relaxation times of articular cartilage of the knee in elite professional football players and age-and BMI-matched amateur athletes.

    Science.gov (United States)

    Behzadi, C; Welsch, G H; Laqmani, A; Henes, F O; Kaul, M G; Schoen, G; Adam, G; Regier, M

    2017-01-01

    Recent investigation has underlined the potential of quantitative MR imaging to be used as a complementary tool for the diagnosis of cartilage degeneration at an early state. The presented study analyses T2* relaxation times of articular cartilage of the knee in professional athletes and compares the results to age- and BMI (Body Mass Index)-matched healthy amateur athletes. 22 professional football players and 22 age- and BMI-matched individuals were underwent knee Magnetic Resonance Imaging (MRI) at 3T including qualitative and quantitative analysis. Qualitative analysis included e.g. meniscal tears, joint effusion and bone edema. For quantitative analysis T2* (22 ET: 4.6-53.6ms) measurements in 3D data acquisition were performed. Deep and superficial layers of 22 predefined cartilage segments were analysed. All data sets were postprocessed using a dedicated software tool. Statistical analysis included Student t-test, confidence intervals and a random effects model. In both groups, T2* relaxation times were significantly higher in the superficial compared to the deep layers (pweight-bearing segments of the lateral superficial femoral condyle (p<0.001). Elevated T2* values in cartilage layers of professional football players compared to amateur athletes were noted. The effects seem to predominate in superficial cartilage layers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Stability of housekeeping genes in human intervertebral disc, endplate and articular cartilage cells in multiple conditions for reliable transcriptional analysis.

    Science.gov (United States)

    Lopa, S; Ceriani, C; Cecchinato, R; Zagra, L; Moretti, M; Colombini, A

    2016-05-27

    Quantitative gene expression analysis is widely used to evaluate the expression of specific tissue markers. To obtain reliable data it is essential to select stable housekeeping genes whose expression is not influenced by the anatomical origin of cells or by the culture conditions. No studies have evaluated housekeeping gene stability in intervertebral disc (IVD) cells and only few studies using cartilaginous endplate (CEP) and articular cartilage (AC) cells are present in the literature. We analysed the stability of four candidate housekeeping genes (GAPDH, TBP, YWHAZ and RPL13A) in human cells isolated from nucleus pulposus (NP) and annulus fibrosus (AF), CEP and AC. Cell isolation, expansion, cryoconservation, and differentiation in 3D pellets were tested. GeNorm, NormFinder, BestKeeper tools and the comparative ΔCt method were used to evaluate housekeeping gene stability. In each cell population, TBP alone or combined with YWHAZ was identified as the best normaliser in both monolayer and 3D pellets. GAPDH was the best performer only for AC cells in monolayer. In most culture conditions considering groups of two or more cell types, TBP was the most stable and YWHAZ was the second choice. GAPDH was the best performer only in 3D pellets with factors for AC and AF combined with CEP cells. RPL13A was the most stable only for AF with CEP cells at isolation. Our findings will be useful to properly design the experimental set-up of studies involving IVD, CEP or AC cells in different culture conditions, in order to obtain accurate and high quality data from quantitative gene expression analysis.

  11. Fully Automatic Analysis of the Knee Articular Cartilage T1ρ relaxation time using Voxel Based Relaxometry

    Science.gov (United States)

    Pedoia, Valentina; Li, Xiaojuan; Su, Favian; Calixto, Nathaniel; Majumdar, Sharmila

    2016-01-01

    Purpose To develop and compare with classical ROI-based approach, a fully-automatic, local and unbiased way of studying the knee T1ρ relaxation time by creating an atlas and using Voxel Based Relaxometry (VBR) in OA and ACL subjects Materials and Methods In this study 110 subjects from 2 cohorts: (i) Mild OA 40 patients with mild-OA KL ≤ 2 and 15 controls KL ≤ 1; (ii) ACL cohort (a model for early OA): 40 ACL-injured patients imaged prior to ACL reconstruction and 1-year post-surgery and 15 controls are analyzed. All the subjects were acquired at 3T with a protocol that includes: 3D-FSE (CUBE) and 3D-T1ρ. A Non-rigid registration technique was applied to align all the images on a single template. This allows for performing VBR to assess local statistical differences of T1ρ values using z-score analysis. VBR results are compared with those obtained with classical ROI-based technique Results ROI-based results from atlas-based segmentation were consistent with classical ROI-based method (CV = 3.83%). Voxel-based group analysis revealed local patterns that were overlooked by ROI-based approach; e.g. VBR showed posterior lateral femur and posterior lateral tibia significant T1ρ elevations in ACL injured patients (sample mean z-score=9.7 and 10.3). Those elevations were overlooked by the classical ROI-based approach (sample mean z-score =1.87, and −1.73) Conclusion VBR is a feasible and accurate tool for the local evaluation of the biochemical composition of knee articular cartilage. VBR is capable of detecting specific local patterns on T1ρ maps in OA and ACL subjects PMID:26443990

  12. Dual effect of platelet lysate on human articular cartilage: a maintenance of chondrogenic potential and a transient proinflammatory activity followed by an inflammation resolution.

    Science.gov (United States)

    Pereira, Rui Cruz; Scaranari, Monica; Benelli, Roberto; Strada, Paolo; Reis, Rui L; Cancedda, Ranieri; Gentili, Chiara

    2013-06-01

    Platelet-rich plasma (PRP), a cocktail of platelet growth factors and bioactive proteins, has been proposed as a therapeutic agent to restore damaged articular cartilage. We report the biological effect of the platelet lysate (PL), a PRP derivative, on primary human articular chondrocytes cultured under both physiological and inflammatory conditions. When added to the culture medium, PL induced a strong mitogenic response in the chondrocytes. The in vitro expanded cell population maintained a chondrogenic redifferentiation potential as revealed by micromass culture in vitro and ectopic cartilage formation in vivo. Further, in chondrocytes cultured in the presence of the proinflammatory cytokine interleukin-1α (IL-1α), the PL induced a drastic enhancement of the synthesis of the cytokines IL-6 and IL-8 and of neutrophil-gelatinase associated lipocalin, a lipocalin expressed during chondrocyte differentiation and inflammation. These events were mediated by the p38 MAP kinase and NF-κB pathways. We observed that inflammatory stimuli activated phospo-MAP kinase-activated protein kinase 2, a direct target of p38. The proinflammatory effect of the PL was a transient phenomenon; after an initial upregulation, we observed significant reduction of the NF-κB activity together with the repression of the inflammatory enzyme cyclooxygenase-2. Moreover, the medium of chondrocytes cultured in the simultaneous presence of PL and IL-1α, showed a significant enhancement of the chemoattractant activity versus untreated chondrocytes. Our findings support the concept that the platelet products have a direct beneficial effect on articular chondrocytes and could drive in sequence a transient activation and the resolution of the inflammatory process, thus providing a rational for their use as therapeutic agents in cartilage inflammation and damage.

  13. Dedifferentiated Human Articular Chondrocytes Redifferentiate to a Cartilage-Like Tissue Phenotype in a Poly(ε-Caprolactone/Self-Assembling Peptide Composite Scaffold

    Directory of Open Access Journals (Sweden)

    Lourdes Recha-Sancho

    2016-06-01

    Full Text Available Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D woven microfiber poly (ε-caprolactone (PCL scaffold with the RAD16-I self-assembling nanofibers to obtain multi-scale functional and biomimetic tissue-engineered constructs. The scaffold was seeded with expanded dedifferentiated human articular chondrocytes and cultured for four weeks in control and chondrogenic growth conditions. The composite constructs were compared to control constructs obtained by culturing cells with 3D woven PCL scaffolds or RAD16-I independently. High viability and homogeneous cell distribution were observed in all three scaffolds used during the term of the culture. Moreover, gene and protein expression profiles revealed that chondrogenic markers were favored in the presence of RAD16-I peptide (PCL/RAD composite or alone under chondrogenic induction conditions. Further, constructs displayed positive staining for toluidine blue, indicating the presence of synthesized proteoglycans. Finally, mechanical testing showed that constructs containing the PCL scaffold maintained the initial shape and viscoelastic behavior throughout the culture period, while constructs with RAD16-I scaffold alone contracted during culture time into a stiffer and compacted structure. Altogether, these results suggest that this new composite scaffold provides important mechanical requirements for a cartilage replacement, while providing a biomimetic microenvironment to re-establish the chondrogenic phenotype of human expanded articular chondrocytes.

  14. Comparison of different material models of articular cartilage in 3D computational modeling of the knee: Data from the Osteoarthritis Initiative (OAI).

    Science.gov (United States)

    Klets, Olesya; Mononen, Mika E; Tanska, Petri; Nieminen, Miika T; Korhonen, Rami K; Saarakkala, Simo

    2016-12-08

    The intricate properties of articular cartilage and the complexity of the loading environment are some of the key challenges in developing models for biomechanical analysis of the knee joint. Fibril-reinforced poroelastic (FRPE) material models have been reported to accurately capture characteristic responses of cartilage during dynamic and static loadings. However, high computational and time costs associated with such advanced models limit applicability of FRPE models when multiple subjects need to be analyzed. If choosing simpler material models, it is important to show that they can still produce truthful predictions. Therefore, the aim of this study was to compare depth-dependent maximum principal stresses and strains within articular cartilage in the 3D knee joint between FRPE material models and simpler isotropic elastic (IE), isotropic poroelastic (IPE) and transversely isotropic poroelastic (TIPE) material models during simulated gait cycle. When cartilage-cartilage contact pressures were matched between the models (15% allowed difference), maximum principal stresses in the IE, IPE and TIPE models were substantially lower than those in the FRPE model (by more than 50%, TIPE model being closest to the FRPE model), and stresses occurred only in compression in the IE model. Additional simulations were performed to find material parameters for the TIPE model (due to its anisotropic nature) that would yield maximum principal stresses similar to the FRPE model. The modified homogeneous TIPE model was in a better agreement with the homogeneous FRPE model, and the average and maximum differences in maximum principal stresses throughout the depth of cartilage were 7% and 9%, respectively, in the lateral compartment and 9% and 11% in the medial compartment. This study revealed that it is possible to match simultaneously maximum principal stresses and strains of cartilage between non-fibril-reinforced and fibril-reinforced knee joint models during gait. Depending on

  15. Calcium signaling of in situ chondrocytes in articular cartilage under compressive loading: Roles of calcium sources and cell membrane ion channels.

    Science.gov (United States)

    Lv, Mengxi; Zhou, Yilu; Chen, Xingyu; Han, Lin; Wang, Liyun; Lu, X Lucas

    2017-10-05

    Mechanical loading on articular cartilage can induce many physical and chemical stimuli on chondrocytes residing in the extracellular matrix (ECM). Intracellular calcium ([Ca2+ ]i ) signaling is among the earliest responses of chondrocytes to physical stimuli, but the [Ca2+ ]i signaling of in situ chondrocytes in loaded cartilage is not fully understood due to the technical challenges in [Ca2+ ]i imaging of chondrocytes in a deforming ECM. This study developed a novel bi-directional microscopy loading device that enables the record of transient [Ca2+ ]i responses of in situ chondrocytes in loaded cartilage. It was found that compressive loading significantly promoted [Ca2+ ]i signaling in chondrocytes with faster [Ca2+ ]i oscillations in comparison to the non-loaded cartilage. Seven [Ca2+ ]i signaling pathways were further investigated by treating the cartilage with antagonists prior to and/or during the loading. Removal of extracellular Ca2+ ions completely abolished the [Ca2+ ]i responses of in situ chondrocytes, suggesting the indispensable role of extracellular Ca2+ sources in initiating the [Ca2+ ]i signaling in chondrocytes. Depletion of intracellular Ca2+ stores, inhibition of PLC-IP3 pathway, and block of purinergic receptors on plasma membrane led to significant reduction in the responsive rate of cells. Three types of ion channels that are regulated by different physical signals, TRPV4 (osmotic and mechanical stress), T-type VGCCs (electrical potential), and mechanical sensitive ion channels (mechanical loading) all demonstrated critical roles in controlling the [Ca2+ ]i responses of in situ chondrocyte in the loaded cartilage. This study provided new knowledge about the [Ca2+ ]i signaling and mechanobiology of chondrocytes in its natural residing environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Evaluation of Labral Pathology and Hip Articular Cartilage in Patients with Femoroacetabular Impingement (FAI): Comparison of Multidetector CT Arthrography and MR Arthrography.

    Science.gov (United States)

    Sahin, Murat; Calisir, Cuneyt; Omeroglu, Hakan; Inan, Ulukan; Mutlu, Fezan; Kaya, Tamer

    2014-01-01

    To compare the multidetector computed tomography (MDCT) arthrography (CTa) and magnetic resonance (MR) arthrography (MRa) findings with surgical findings in patients with femoroacetabular impingement (FAI) and to evaluate the diagnostic performance of these methods. Labral pathology and articular cartilage were prospectively evaluated with MRa and CTa in 14 hips of 14 patients. The findings were evaluated by two musculoskeletal radiologists with 10 and 20 years of experience, respectively. Sensitivity, specificity, accuracy, and positive predictive value were determined using surgical findings as the standard of reference. While the disagreement between observers was recorded in two cases of labral tearing with MRa, there was a complete consensus with CTa. Disagreement between observers was found in four cases of femoral cartilage loss with both MRa and CTa. Disagreement was also recorded in only one case of acetabular cartilage loss with both methods. The percent sensitivity, specificity, and accuracy for correctly assessing the labral tearing were as follows for MRa/CTa, respectively: 100/100, 50/100, 86/100 (p0.05) and for femoral cartilage assessment were 100/75, 90/70, 86/71 (p>0.05). Inter-observer reliability value showed excellent agreement for labral tearing with CTa (κ=1.0). Inter-observer agreement was substantial to excellent with regard to acetabular cartilage assessment with MRa and CTa (κ=0.76 for MRa and κ=0.86 for CTa). Inter-observer reliability with CTa is excellent for labral tearing assessment. CTa seems to have an equal sensitivity and a higher specificity than MRa for the detection of labral pathology. MRa is better, but not statistically significantly, in demonstrating acetabular and femoral cartilage pathology.

  17. Comparison of Two Methods for Calculating the Frictional Properties of Articular Cartilage Using a Simple Pendulum and Intact Mouse Knee Joints

    Science.gov (United States)

    Drewniak, Elizabeth I.; Jay, Gregory D.; Fleming, Braden C.; Crisco, Joseph J.

    2009-01-01

    In attempts to better understand the etiology of osteoarthritis, a debilitating joint disease that results in the degeneration of articular cartilage in synovial joints, researchers have focused on joint tribology, the study of joint friction, lubrication, and wear. Several different approaches have been used to investigate the frictional properties of articular cartilage. In this study, we examined two analysis methods for calculating the coefficient of friction (μ) using a simple pendulum system and BL6 murine knee joints (n=10) as the fulcrum. A Stanton linear decay model (Lin μ) and an exponential model that accounts for viscous damping (Exp μ) were fit to the decaying pendulum oscillations. Root mean square error (RMSE), asymptotic standard error (ASE), and coefficient of variation (CV) were calculated to evaluate the fit and measurement precision of each model. This investigation demonstrated that while Lin μ was more repeatable, based on CV (5.0% for Lin μ; 18% for Exp μ), Exp μ provided a better fitting model, based on RMSE (0.165° for Exp μ; 0.391° for Lin μ) and ASE (0.033 for Exp μ; 0.185 for Lin μ), and had a significantly lower coefficient of friction value (0.022±0.007 for Exp μ; 0.042±0.016 for Lin μ) (p=0.001). This study details the use of a simple pendulum for examining cartilage properties in situ that will have applications investigating cartilage mechanics in a variety of species. The Exp μ model provided a more accurate fit to the experimental data for predicting the frictional properties of intact joints in pendulum systems. PMID:19632680

  18. The search for negative amplitude components in quasi-continuous distributions of relaxation times: the example of 1H magnetization exchange in articular cartilage and hydrated collagen

    Science.gov (United States)

    Fantazzini, Paola; Galassi, Francesca; Bortolotti, Villiam; Brown, Robert J. S.; Vittur, Franco

    2011-06-01

    When inverting nuclear magnetic resonance relaxation data in order to obtain quasi-continuous distributions of relaxation times for fluids in porous media, it is common practice to impose a non-negative (NN) constraint on the distributions. While this approach can be useful in reducing the effects of data distortion and/or preventing wild oscillations in the distributions, it may give misleading results in the presence of real negative amplitude components. Here, some examples of valid negative components for articular cartilage and hydrated collagen are given. Articular cartilage is a connective tissue, consisting mainly of collagen, proteoglycans and water, which can be considered, in many aspects, as a porous medium. Separate T1 relaxation data are obtained for low-mobility ('solid') macromolecular 1H and for higher-mobility ('liquid') 1H by the separation of these components in free induction decays, with α denoting the solid/liquid 1H ratio. When quasi-continuous distributions of relaxation times (T1) of the solid and liquid signal components of cartilage or collagen are computed from experimental relaxation data without imposing the usual NN constraint, valid negative peaks may appear. The features of the distributions, in particular negative peaks, and the fact that peaks at longer times for macromolecular and water protons are at essentially the same T1, are interpreted as the result of a magnetization exchange between these two spin pools. For the only-slightly-hydrated collagen samples, with α>1, the exchange leads to small negative peaks at short T1 times for the macromolecular component. However, for the cartilage, with substantial hydration or for a strongly hydrated collagen sample, both with αLt1, the behavior is reversed, with a negative peak for water at short times. The validity of a negative peak may be accepted (dismissed) by a high (low) cost of NN in error of fit. Computed distributions for simulated data using observed signal

  19. A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2).

    Science.gov (United States)

    Tamai, Noriyuki; Myoui, Akira; Hirao, Makoto; Kaito, Takashi; Ochi, Takahiro; Tanaka, Junzo; Takaoka, Kunio; Yoshikawa, Hideki

    2005-05-01

    Articular cartilage repair remains a major obstacle in tissue engineering. We recently developed a novel tool for articular cartilage repair, consisting of a triple composite of an interconnected porous hydroxyapatite (IP-CHA), recombinant human bone morphogenetic protein-2 (rhBMP-2), and a synthetic biodegradable polymer [poly-d,l-lactic acid/polyethylene glycol (PLA-PEG)] as a carrier for rhBMP-2. In the present study, we evaluated the capacity of the triple composite to induce the regeneration of articular cartilage. Full-thickness cartilage defects were created in the trochlear groove of 52 New Zealand White rabbits. Sixteen defects were filled with the bone morphogenetic protein (BMP)/PLA-PEG/IP-CHA composite (group I), 12 with PLA-PEG/IP-CHA (group II), 12 with IP-CHA alone (group III), and 12 were left empty (group IV). The animals were killed 1, 3, and 6 weeks after surgery, and the gross appearance of the defect sites was assessed. The harvested tissues were examined radiographically and histologically. One week after implantation with the BMP/PLA-PEG/IP-CHA composite (group I), vigorous repair had occurred in the subchondral defect. It contained an agglomeration of mesenchymal cells which had migrated from the surrounding bone marrow either directly, or indirectly via the interconnecting pores of the IP-CHA scaffold. At 6 weeks, these defects were completely repaired. The regenerated cartilage manifested a hyaline-like appearance, with a mature matrix and a columnar organization of chondrocytes. The triple composite of rhBMP-2, PLA-PEG, and IP-CHA promotes the repair of full-thickness articular cartilage defects within as short a period as 3 weeks in the rabbit model. Hence, this novel cell-free implant biotechnology could mark a new development in the field of articular cartilage repair.

  20. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation

    DEFF Research Database (Denmark)

    Sondergaard, B-C; Schultz, N; Madsen, S H

    2010-01-01

    Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated ......Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase......-mediated cartilage degradation....

  1. Contour interpolated radial basis functions with spline boundary correction for fast 3D reconstruction of the human articular cartilage from MR images

    Energy Technology Data Exchange (ETDEWEB)

    Javaid, Zarrar; Unsworth, Charles P., E-mail: c.unsworth@auckland.ac.nz [Department of Engineering Science, The University of Auckland, Auckland 1010 (New Zealand); Boocock, Mark G.; McNair, Peter J. [Health and Rehabilitation Research Center, Auckland University of Technology, Auckland 1142 (New Zealand)

    2016-03-15

    Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a “near real-time” 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage. Methods: The authors introduce a novel fusion of an adaptation of the contour method known as “contour interpolation (CI)” with radial basis functions (RBFs) which they describe as “CI-RBFs.” The authors also present a spline boundary correction which further enhances volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the volume

  2. Protection of the medial femoral condyle articular cartilage during drilling of the femoral tunnel through the accessory medial portal in anatomic anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Abdelkafy, Ashraf

    2012-12-01

    Accurate positioning of the femoral tunnel in the native femoral anterior cruciate ligament (ACL) footprint requires drilling through an accessory medial portal (AMP). The AMP is located far medial and at a low level. Despite the benefits of drilling through the AMP, it is possible that the drill bit head will injure the articular cartilage of the medial femoral condyle as it slides along the guide pin to the femoral insertion of the ACL. Because more surgeons are now performing anatomic ACL reconstructions and shifting from transtibial drilling toward transportal drilling, the risk of this injury might be increasing, especially during the beginning of their learning curve. To avoid such injury, a bio-interference screw sheath is used. It is inserted through the AMP over the guide pin until it reaches near the medial wall of the lateral femoral condyle. The drill bit is inserted over the guide pin and through the bio-interference screw sheath. Using the bio-interference screw sheath not only protects the articular cartilage of the medial femoral condyle but also protects the medial meniscus, posterior cruciate ligament, and skin of the AMP from injury because of the close proximity of the drill bit head to these structures during transportal drilling.

  3. Degeneration of articular cartilage in osteonecrosis of the femoral head begins at the necrotic region after collapse: a preliminary study using T1 rho MRI

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Kazuhiko; Motomura, Goro; Nakashima, Yasuharu [Kyushu University, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Kawanami, Satoshi; Takayama, Yukihisa; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Yamamoto, Takuaki [Fukuoka University, Department of Orthopaedic Surgery, Faculty of Medicine, Jonan-ku, Fukuoka (Japan)

    2017-04-15

    The purpose of this study is to evaluate the role of collapse on the degeneration of articular cartilage in patients with osteonecrosis of the femoral head (ONFH). Sixteen hips in 12 patients (four men, eight women; mean age, 34.8 years) with a history of systemic corticosteroid treatment were studied using T1 rho magnetic resonance imaging (MRI). Six hips had collapsed ONFH, five had non-collapsed ONFH, and five had no osteonecrosis (controls). Using oblique coronal images, we divided the articular surface of necrotic femoral heads into a region just above the necrotic bone (necrotic zone) and another above the living bone (living zone). T1 rho value was evaluated for each zone. The mean T1 rho value in the necrotic zone was significantly higher in the collapsed ONFH group (48.4 ± 2.7 ms) than in the non-collapsed ONFH group (41.0 ± 0.9 ms). In the collapsed ONFH group, the mean T1 rho value was significantly higher in the necrotic zone (48.4 ± 2.7 ms) than in the living zone (43.5 ± 2.5 ms). In the non-collapsed ONFH group, there was no significant difference between the mean T1 rho values of the necrotic and living zones. In the collapsed ONFH group, the mean T1 rho value of the necrotic zone and the interval from pain onset to the MRI examination were positively correlated. The current T1 rho MRI study suggested that the degeneration of articular cartilage in ONFH begins at the necrotic region after collapse. (orig.)

  4. Dangguijihwang-tang and Dangguijakyak-san Prevent Menopausal Symptoms and Dangguijihwang-tang Prevents Articular Cartilage Deterioration in Ovariectomized Obese Rats with Monoiodoacetate-Induced Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Hye Won Lee

    2017-01-01

    Full Text Available We investigated whether dangguijakyak-san (DJY and dangguijihwang-tang (DJH, oriental medicines traditionally used for inflammatory diseases, could prevent and/or delay the progression of postmenopausal symptoms and osteoarthritis in osteoarthritis-induced estrogen-deficient rats. Treated ovariectomized (OVX rats consumed either 1% DJY or 1% DJH in the diets. Positive-control rats were given 30 μg/kg bw 17β-estradiol and control rats were given 1% fat as were the normal-control rats. All rats received high-fat diets for 8 weeks. At the 9th week, OVX rats received articular injections of monoiodoacetate (MIA or saline (normal control into the right knee. At 3 weeks after MIA injection, DJY reduced visceral-fat mass and improved glucose metabolism by reducing insulin resistance, whereas DJH increased BMD and decreased insulin resistance. DJH improved weight distribution in the right knee and maximum running velocity on a treadmill at days 14 and 21 as much as those of the positive control. TNF-α, IL-1β, and IL-6 levels in articular cartilage were much higher in the control than the positive control, whereas both DJY and DJH reduced the levels to those of the positive control. The histological analysis assessed articular cartilage damage near the tidemark and proteoglycan loss in the control versus the positive control; DJY and DJH prevented this damage and proteoglycan loss. In conclusion, DJY may provide an effective treatment for improving glucose tolerance, and DJH may be appropriate for preventing osteoarthritis.

  5. Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737orpk mice lacking the primary cilia protein polaris.

    Science.gov (United States)

    McGlashan, S R; Haycraft, C J; Jensen, C G; Yoder, B K; Poole, C A

    2007-05-01

    Primary cilia are highly conserved organelles found on almost all eukaryotic cells. Tg737(orpk) (orpk) mice carry a hypomorphic mutation in the Tg737 gene resulting in the loss of polaris, a protein essential for ciliogenesis. Orpk mice have an array of skeletal patterning defects and show stunted growth after birth, suggesting defects in appositional and endochondral development. This study investigated the association between orpk tibial long bone growth and chondrocyte primary cilia expression using histomorphometric and immunohistochemical analysis. Wild-type chondrocytes throughout the developing epiphysis and growth plate expressed primary cilia, which showed a specific orientation away from the articular surface in the first 7-10 cell layers. In orpk mice, primary cilia were identified on very few cells and were significantly shorter. Orpk chondrocytes also showed significant increases in cytoplasmic tubulin, a likely result of failed ciliary assembly. The growth plates of orpk mice were significantly smaller in length and width, with marked changes in cellular organization in the presumptive articular cartilage, proliferative and hypertrophic zones. Cell density at the articular surface and in the hypertrophic zone was significantly altered, suggesting defects in both appositional and endochondral growth. In addition, orpk hypertrophic chondrocytes showed re-organization of the F-actin network into stress fibres and failed to fully undergo hypertrophy, while there was a marked reduction in type X collagen sequestration. These data suggest that failure to form a functional primary cilium affects chondrocyte differentiation and results in delayed chondrocyte hypertrophy within the orpk growth plate.

  6. Assessment of chemical species of lead accumulated in tidemarks of human articular cartilage by X-ray absorption near-edge structure analysis

    Energy Technology Data Exchange (ETDEWEB)

    Meirer, Florian [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); MiNALab, CMM-Irst, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Trento (Italy); Pemmer, Bernhard, E-mail: bpemmer@ati.ac.at [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); Pepponi, Giancarlo [MiNALab, CMM-Irst, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Trento (Italy); Zoeger, Norbert; Wobrauschek, Peter [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); Sprio, Simone; Tampieri, Anna [Istituto di Scienza e Tecnologia dei Materiali Ceramici CNR, Faenca (Italy); Goettlicher, Joerg; Steininger, Ralph; Mangold, Stefan [Institute for Synchrotron Radiation, Karlsruhe Institute of Technology, Campus South, 76344 Eggenstein-Leopoldshafen (Germany); Roschger, Paul [Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna (Austria); Berzlanovich, Andrea [Department of Forensic Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Hofstaetter, Jochen G. [Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna (Austria); Department of Orthopaedics, Vienna General Hospital, Medical University of Vienna, A-1090 Vienna (Austria); Streli, Christina [Atominstitut, Vienna University of Technology, 1020 Wien (Austria)

    2011-03-01

    Lead is a toxic trace element that shows a highly specific accumulation in the transition zone between calcified and non-calcified articular cartilage, the so-called ‘tidemark’. Excellent agreement has been found between XANES spectra of synthetic Pb-doped carbonated hydroxyapatite and spectra obtained in the tidemark region and trabecular bone of normal human samples, confirming that in both tissues Pb is incorporated into the hydroxyapatite crystal structure of bone. During this study the µ-XANES set-up at the SUL-X beamline at ANKA was tested and has proven to be well suited for speciation of lead in human mineralized tissue samples. A highly specific accumulation of the toxic element lead was recently measured in the transition zone between non-calcified and calcified normal human articular cartilage. This transition zone, the so-called ‘tidemark’, is considered to be an active calcification front of great clinical importance. However, little is known about the mechanisms of accumulation and the chemical form of Pb in calcified cartilage and bone. Using spatially resolved X-ray absorption near-edge structure analysis (µ-XANES) at the Pb L{sub 3}-edge, the chemical state of Pb in the osteochondral region was investigated. The feasibility of the µ-XANES set-up at the SUL-X beamline (ANKA synchrotron light source) was tested and confirmed by comparing XANES spectra of bulk Pb-reference compounds recorded at both the XAS and the SUL-X beamline at ANKA. The µ-XANES set-up was then used to investigate the tidemark region of human bone (two patella samples and one femoral head sample). The spectra recorded at the tidemark and at the trabecular bone were found to be highly correlated with the spectra of synthetic Pb-doped carbonated hydroxyapatite, suggesting that in both of these very different tissues Pb is incorporated into the hydroxyapatite structure.

  7. Texture analysis of articular cartilage traumatic changes in the knee calculated from morphological 3.0 T MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Boutsikou, Konstantina [Department of Medical Radiologic Technology, Technological Educational Institute of Athens, Ag.Spyridonos, Egaleo, Athens 12210 (Greece); Kostopoulos, Spiros; Glotsos, Dimitris; Cavouras, Dionisis [Department of Medical Instruments Technology, Technological Educational Institute of Athens, Ag.Spyridonos, Egaleo, Athens 12210 (Greece); Lavdas, Eleftherios; Oikonomou, Georgia [Department of Medical Radiologic Technology, Technological Educational Institute of Athens, Ag.Spyridonos, Egaleo, Athens 12210 (Greece); Malizos, Konstantinos [Department of Orthopaedic Surgery, University of Thessaly, School of Health Sciences, University Hospital of Larissa, Biopolis, Larissa 41110 (Greece); Fezoulidis, Ioannis V. [Department of Radiology, University of Thessaly, School of Health Sciences, University Hospital of Larissa, Biopolis, Larissa 41110 (Greece); Vlychou, Marianna, E-mail: mvlychou@med.uth.gr [Department of Radiology, University of Thessaly, School of Health Sciences, University Hospital of Larissa, Biopolis, Larissa 41110 (Greece)

    2013-08-15

    Objectives: In the present work, we aim to identify changes in the cartilage texture of the injured knee in young, physically active, patients by computer analysis of MRI images based on 3.0 T morphological sequences. Methods: Fifty-three young patients with training injury or trauma in one knee underwent MRI and arthroscopy. Textural features were computed from the MRI images of the knee-cartilages and two classes were formed of 28 normal and 16 with pathology only in the medial femoral condyle (MFC) cartilage. Results: Textural features with statistically significant differences between the two classes were found only at the MFC and the medial tibial condyle (MTC) areas. Three features-combinations, at the MFC or the MTC, maximized the between classes separation, thus, rendering alterations in cartilage texture due to injury more evident. The MFC cartilage in the pathology class was found more inhomogeneous in the distribution of gray-levels and of lower texture anisotropy and the opposed MTC cartilage, though normal on MRI and arthroscopy, was found to have lower texture anisotropy than cartilage in the normal class. Conclusion: Texture analysis may be used as an adjunct to morphological MR imaging for improving the detection of subtle cartilage changes and contributes to early therapeutic approach.

  8. Isolated effects of external bath osmolality, solute concentration, and electrical charge on solute transport across articular cartilage

    NARCIS (Netherlands)

    Pouran, Behdad; Arbabi, Vahid; Zadpoor, Amir A.; Weinans, Harrie

    2016-01-01

    © 2016 IPEMThe metabolic function of cartilage primarily depends on transport of solutes through diffusion mechanism. In the current study, we use contrast enhanced micro-computed tomography to determine equilibrium concentration of solutes through different cartilage zones and solute flux in the

  9. Cartilage imaging in sports medicine.

    Science.gov (United States)

    Black, Brandon R; Chong, Le Roy; Potter, Hollis G

    2009-03-01

    Magnetic resonance imaging (MRI) using cartilage-sensitive sequences has been shown to be an accurate, noninvasive method by which to detect articular cartilage injury and early degeneration. These are important management considerations in an athletic population. The advantages of MRI include the lack of ionizing radiation, direct multiplanar capabilities and high-contrast resolution of articular soft tissue structures. The present review details imaging strategies for assessing cartilage in the athletic population, defines the normal MRI appearance of articular cartilage, and illustrates the spectrum of articular cartilage lesions seen in various joints of the body.

  10. Relationship between knee alignment and T1ρ values of articular cartilage and menisci in patients with knee osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ligong, E-mail: ligong.wang@hotmail.com [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016 (United States); School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, Jiangsu 215123 (China); Vieira, Renata La Rocca, E-mail: relarocca@gmail.com [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016 (United States); Rybak, Leon D., E-mail: Leon.Rybak@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016 (United States); Babb, James S., E-mail: James.Babb@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016 (United States); Chang, Gregory, E-mail: gregory.chang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY 10016 (United States); Krasnokutsky, Svetlana, E-mail: Svetlana.Krasnokutsky@nyumc.org [Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10003 (United States); Abramson, Steven, E-mail: StevenB.Abramson@nyumc.org [Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10003 (United States); and others

    2013-11-01

    Objective: To assess the relationship between knee alignment and subregional T1ρ values of the femorotibial cartilage and menisci in patients with mild (Kellgren–Lawrence grade 1) to moderate (KL3) osteoarthritis (OA) at 3 T. Materials and methods: 26 subjects with a clinical diagnosis of KL1-3 OA were included and subdivided into three subgroups: varus, valgus, and neutral. All subjects were evaluated on a 3 T MR scanner. Mann–Whitney and Wilcoxon signed rank tests were performed to determine any statistically significant differences in subregional T1ρ values of femorotibial cartilage and menisci among the three subgroups of KL1-3 OA patients. Results: Medial femoral anterior cartilage subregion in varus group had significantly higher (p < 0.05) T1ρ values than all cartilage subregions in valgus group. Medial tibial central cartilage subregion had significantly higher T1ρ values (p < 0.05) than lateral tibial central cartilage subregion in varus group. The posterior horn of the medial meniscus in neutral group had significantly higher T1ρ values (p < 0.0029) than all meniscus subregions in valgus group. Conclusion: There exists some degree of association between knee alignment and subregional T1ρ values of femorotibial cartilage and menisci in patients with clinical OA.

  11. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  12. The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model

    DEFF Research Database (Denmark)

    He, Yi; Zheng, Qinlong; Simonsen, Ole

    2013-01-01

    a monoclonal antibody against this neoepitope of active ADAMTS-4. Furthermore, we established and characterized a competitive ELISA for measuring active ADAMTS-4 form applying the specific antibody. We used this assay to profile the presence of active ADAMTS-4 and its aggrecan degradation product (NITEGE(373......)) in a bovine cartilage ex vivo model. We found that after stimulation with catabolic factors, the cartilage initially released high levels of aggrecanase-derived aggrecan fragments into supernatant but subsequently decreased to background levels. The level of active ADAMTS-4 released into the supernatant...... of osteoarthritis stained strongly for active ADAMTS-4 where surface fibrillation and clustered chondrocytes were observed. This assay could be an effective tool for studying ADAMTS-4 activity and for screening drugs regulating ADAMTS-4 activation. Moreover, it could be a potential biomarker for degenerative joint...

  13. Implementation of a gait cycle loading into healthy and meniscectomised knee joint models with fibril-reinforced articular cartilage.

    Science.gov (United States)

    Mononen, Mika E; Jurvelin, Jukka S; Korhonen, Rami K

    2015-01-01

    Computational models can be used to evaluate the functional properties of knee joints and possible risk locations within joints. Current models with fibril-reinforced cartilage layers do not provide information about realistic human movement during walking. This study aimed to evaluate stresses and strains within a knee joint by implementing load data from a gait cycle in healthy and meniscectomised knee joint models with fibril-reinforced cartilages. A 3D finite element model of a knee joint with cartilages and menisci was created from magnetic resonance images. The gait cycle data from varying joint rotations, translations and axial forces were taken from experimental studies and implemented into the model. Cartilage layers were modelled as a fibril-reinforced poroviscoelastic material with the menisci considered as a transversely isotropic elastic material. In the normal knee joint model, relatively high maximum principal stresses were specifically predicted to occur in the medial condyle of the knee joint during the loading response. Bilateral meniscectomy increased stresses, strains and fluid pressures in cartilage on the lateral side, especially during the first 50% of the stance phase of the gait cycle. During the entire stance phase, the superficial collagen fibrils modulated stresses of cartilage, especially in the medial tibial cartilage. The present computational model with a gait cycle and fibril-reinforced biphasic cartilage revealed time- and location-dependent differences in stresses, strains and fluid pressures occurring in cartilage during walking. The lateral meniscus was observed to have a more significant role in distributing loads across the knee joint than the medial meniscus, suggesting that meniscectomy might initiate a post-traumatic process leading to osteoarthritis at the lateral compartment of the knee joint.

  14. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

    NARCIS (Netherlands)

    Verzijl, N.; Groot, J. de; Zaken, C.B.; Braun-Benjamin, O.; Maroudas, A.; Bank, R.A.; Mizrahi, J.; Schalkwijk, C.G.; Thorpe, S.R.; Baynes, J.W.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.; TeKoppele, J.M.

    2002-01-01

    Objective. Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular

  15. Effects of unloading on knee articular cartilage T1rho and T2 magnetic resonance imaging relaxation times: a case series.

    Science.gov (United States)

    Souza, Richard B; Baum, Thomas; Wu, Samuel; Feeley, Brian T; Kadel, Nancy; Li, Xiaojuan; Link, Thomas M; Majumdar, Sharmila

    2012-06-01

    Case series. It has been shown in rodent and canine models that cartilage composition is significantly altered in response to long-term unloading. To date, however, no in vivo human studies have investigated this topic. The objective of this case series was to determine the influence of unloading and reloading on T1rho and T2 relaxation times of articular cartilage in healthy young joints. Ten patients who required 6 to 8 weeks of non-weight bearing (NWB) for injuries affecting the distal lower extremity participated in the study. Quantitative T1rho and T2 imaging of the ipsilateral knee joint was performed at 3 time points: (1) prior to surgery (baseline), (2) immediately after a period of NWB (post-NWB), and (3) after 4 weeks of full weight bearing (post-FWB). Cartilage regions of interest were segmented and overlaid on T1rho and T2 relaxation time maps for quantification. Descriptive statistics are provided for all changes. Increases of 5% to 10% in T1rho times of all femoral and tibial compartments were noted post-NWB. All values returned to near-baseline levels post-FWB. Increases in medial tibia T2 times were noted post-NWB and remained elevated post-FWB. The load-bearing regions showed the most significant changes in response to unloading, with increases of up to 12%. The observation of a transient shift in relaxation times confirms that cartilage composition is subject to alterations based on loading conditions. These changes appear to be mostly related to proteoglycan content and more localized to the load-bearing regions. However, following 4 weeks of full weight bearing, relaxation times of nearly all regions had returned to baseline levels, demonstrating reversibility in compositional fluctuations. Therapy, level 4.

  16. A comparison of multi-echo spin-echo and triple-echo steady-state T2 mapping for in vivo evaluation of articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Juras, Vladimir; Szomolanyi, Pavol [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Institute of Measurement Science, Department of Imaging Methods, Bratislava (Slovakia); Bohndorf, Klaus; Kronnerwetter, Claudia; Hager, Benedikt; Zbyn, Stefan [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Heule, Rahel; Bieri, Oliver [University of Basel Hospital, Division of Radiological Physics, Department of Radiology, Basel (Switzerland); Trattnig, Siegfried [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria)

    2016-06-15

    To assess the clinical relevance of T{sub 2} relaxation times, measured by 3D triple-echo steady-state (3D-TESS), in knee articular cartilage compared to conventional multi-echo spin-echo T{sub 2}-mapping. Thirteen volunteers and ten patients with focal cartilage lesions were included in this prospective study. All subjects underwent 3-Tesla MRI consisting of a multi-echo multi-slice spin-echo sequence (CPMG) as a reference method for T{sub 2} mapping, and 3D TESS with the same geometry settings, but variable acquisition times: standard (TESSs 4:35min) and quick (TESSq 2:05min). T{sub 2} values were compared in six different regions in the femoral and tibial cartilage using a Wilcoxon signed ranks test and the Pearson correlation coefficient (r). The local ethics committee approved this study, and all participants gave written informed consent. The mean quantitative T{sub 2} values measured by CPMG (mean: 46±9ms) in volunteers were significantly higher compared to those measured with TESS (mean: 31±5ms) in all regions. Both methods performed similarly in patients, but CPMG provided a slightly higher difference between lesions and native cartilage (CPMG: 90ms→61ms [31%],p=0.0125;TESS 32ms→24ms [24%],p=0.0839). 3D-TESS provides results similar to those of a conventional multi-echo spin-echo sequence with many benefits, such as shortening of total acquisition time and insensitivity to B{sub 1} and B{sub 0} changes. (orig.)

  17. Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints.

    Science.gov (United States)

    Shahin, Kifah; Doran, Pauline M

    2012-04-01

    The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II. Copyright © 2011 Wiley Periodicals, Inc.

  18. Isolated effects of external bath osmolality, solute concentration, and electrical charge on solute transport across articular cartilage.

    Science.gov (United States)

    Pouran, Behdad; Arbabi, Vahid; Zadpoor, Amir A; Weinans, Harrie

    2016-12-01

    The metabolic function of cartilage primarily depends on transport of solutes through diffusion mechanism. In the current study, we use contrast enhanced micro-computed tomography to determine equilibrium concentration of solutes through different cartilage zones and solute flux in the cartilage, using osteochondral plugs from equine femoral condyles. Diffusion experiments were performed with two solutes of different charge and approximately equal molecular weight, namely iodixanol (neutral) and ioxaglate (charge=-1) in order to isolate the effects of solute's charge on diffusion. Furthermore, solute concentrations as well as bath osmolality were changed to isolate the effects of steric hindrance on diffusion. Bath concentration and bath osmolality only had minor effects on the diffusion of the neutral solute through cartilage at the surface, middle and deep zones, indicating that the diffusion of the neutral solute was mainly Fickian. The negatively charged solute diffused considerably slower through cartilage than the neutral solute, indicating a large non-Fickian contribution in the diffusion of charged molecules. The numerical models determined maximum solute flux in the superficial zone up to a factor of 2.5 lower for the negatively charged solutes (charge=-1) as compared to the neutral solutes confirming the importance of charge-matrix interaction in diffusion of molecules across cartilage. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

    Science.gov (United States)

    Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

    2013-05-01

    Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

  20. Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning.

    Science.gov (United States)

    Swan, Anna L; Hillier, Kirsty L; Smith, Julia R; Allaway, David; Liddell, Susan; Bacardit, Jaume; Mobasheri, Ali

    2013-12-13

    Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions. This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified. BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein. Using this

  1. Genipin crosslinking of cartilage enhances resistance to biochemical degradation and mechanical wear.

    Science.gov (United States)

    McGann, Megan E; Bonitsky, Craig M; Jackson, Mariah L; Ovaert, Timothy C; Trippel, Stephen B; Wagner, Diane R

    2015-11-01

    Collagen crosslinking enhances many beneficial properties of articular cartilage, including resistance to chemical degradation and mechanical wear, but many crosslinking agents are cytotoxic. The purpose of this study was to evaluate the effectiveness of genipin, a crosslinking agent with favorable biocompatibility and cytotoxicity, as a potential treatment to prevent the degradation and wear of articular cartilage. First, the impact of genipin concentration and treatment duration on the viscoelastic properties of bovine articular cartilage was quantified. Next, two short-term (15 min) genipin crosslinking treatments were chosen, and the change in collagenase digestion, cartilage wear, and the friction coefficient of the tissue with these treatments was measured. Finally, chondrocyte viability after exposure to these genipin treatments was assessed. Genipin treatment increased the stiffness of healthy, intact cartilage in a dose-dependent manner. The 15-min crosslinking treatments improved cartilage's resistance to both chemical degradation, particularly at the articular surface, and to damage due to mechanical wear. These enhancements were achieved without sacrificing the low coefficient of friction of the tissue and at a genipin dose that preserved chondrocyte viability. The results of this study suggest that collagen crosslinking via genipin may be a promising preventative treatment to slow the degradation of cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. Robust and general method for determining surface fluid flow boundary conditions in articular cartilage contact mechanics modeling.

    Science.gov (United States)

    Pawaskar, Sainath Shrikant; Fisher, John; Jin, Zhongmin

    2010-03-01

    Contact detection in cartilage contact mechanics is an important feature of any analytical or computational modeling investigation when the biphasic nature of cartilage and the corresponding tribology are taken into account. The fluid flow boundary conditions will change based on whether the surface is in contact or not, which will affect the interstitial fluid pressurization. This in turn will increase or decrease the load sustained by the fluid phase, with a direct effect on friction, wear, and lubrication. In laboratory experiments or clinical hemiarthroplasty, when a rigid indenter or metallic prosthesis is used to apply load to the cartilage, there will not be any fluid flow normal to the surface in the contact region due to the impermeable nature of the indenter/prosthesis. In the natural joint, on the other hand, where two cartilage surfaces interact, flow will depend on the pressure difference across the interface. Furthermore, in both these cases, the fluid would flow freely in non-contacting regions. However, it should be pointed out that the contact area is generally unknown in advance in both cases and can only be determined as part of the solution. In the present finite element study, a general and robust algorithm was proposed to decide nodes in contact on the cartilage surface and, accordingly, impose the fluid flow boundary conditions. The algorithm was first tested for a rigid indenter against cartilage model. The algorithm worked well for two-dimensional four-noded and eight-noded axisymmetric element models as well as three-dimensional models. It was then extended to include two cartilages in contact. The results were in excellent agreement with the previous studies reported in the literature.

  3. [Histological, biochemical and spectroscopic changes of articular cartilage in osteoarthritis: is there a chance for spectroscopic evaluation?].

    Science.gov (United States)

    Pester, J K; Stumpfe, S T; Steinert, S; Marintschev, I; Plettenberg, H K; Aurich, M; Hofmann, G O

    2014-10-01

    Non-destructive techniques for the detection and classification of pathological changes of cartilage in the early stages of osteoarthritis are required for arthroscopic and open surgery of joints. Biochemical and histological changes in cartilage with different degrees of destruction were analysed and correlated to changes in the spectroscopic characteristics of cartilage. 24 patients (n = 25 knees) with severely destructed knee joints received total knee replacement. The cartilage of the resected joints was classified according to the ICRS system. Defined cartilage specimens were investigated spectroscopically employing NIRS (near-infrared spectroscopy). In the following the cartilage specimens were harvested to determine the content of proteoglycan (GAG) and hydroxyproline (HP) as an essential part of collagen. Histological evaluation of the Mankin score and Otte score was performed using haematoxylin/eosin and safranin-O staining. Spearman's rank correlation coefficient was used to characterise links between the parameters investigated. We found significant correlations between spectroscopic, histological and biochemical characteristics. NIRS corresponded to the content of GAG (ρ = 0.58) and HP (ρ = 0.59), as well as to the Mankin (ρ = 0.55) and Otte (ρ = 0.5) scores. Furthermore, the ICRS classification correlated with histological evaluation (Mankin score ρ = 0.725 and Otte score ρ = 0.736), as to be expected. Characteristic cartilage changes in different degrees of osteoarthritis can be detected and evaluated by the spectroscopic method NIRS as a non-destructive technique. However, the quality of this technical evaluation cannot compete with biochemical and histological analysis. Georg Thieme Verlag KG Stuttgart · New York.

  4. Effect of intra-articular injection of intermediate-weight hyaluronic acid on hip and knee cartilage: in-vivo evaluation using T2 mapping.

    Science.gov (United States)

    Ferrero, Giulio; Sconfienza, Luca Maria; Fiz, Francesco; Fabbro, Emanuele; Corazza, Angelo; Dettore, Daniele; Orlandi, Davide; Castellazzo, Carlo; Tornago, Stefano; Serafini, Giovanni

    2018-01-09

    We used T2 mapping to quantify the effect of intra-articular hyaluronic acid administration (IAHAA) on cartilage with correlation to clinical symptoms. One hundred two patients with clinical and MRI diagnosis of hip or knee grade I-III chondropathy were prospectively included. All patients received a standard MRI examination of the affected hip/knee (one joint/patient) and T2-mapping multiecho sequence for cartilage evaluation. T2 values of all slices were averaged and used for analysis. One month after MR evaluation 72 patients (38 males; mean age 51±10 years) underwent IAHAA. As a control group, 30 subjects (15 males; 51 ± 9 years) were not treated. MR and WOMAC evaluation was performed at baseline and after 3, 9, and 15 months in all patients. T2 mapping in hyaluronic acid (HA) patients showed a significant increase in T2 relaxation times from baseline to the first time point after therapy in knees (40.7 ± 9.8 ms vs. 45.8 ± 8.6 ms) and hips (40.9 ± 9.7 ms; 45.9 ± 9.5 ms) (p < 0.001). At the 9- and 15-month evaluations, T2 relaxation dropped to values similar to the baseline ones (p < 0.001 vs. 3 month). The correlation between T2 increase and pain reduction after IAHAA was statistically significant (r = 0.54, p < 0.01) in patients with grade III chondropathy. T2 mapping can be used to evaluate the effect over time of IAHAA in patients with hip and knee chondropathy. • T2 relaxation times change over time after hyaluronic acid intra-articular administration • T2 relaxation times of the medial femoral condyle correlate with WOMAC variation • T2 relaxation times are different between Outerbridge I and II-III.

  5. Effectiveness of an aquatic exercise program and low-level laser therapy on articular cartilage in an experimental model of osteoarthritis in rats.

    Science.gov (United States)

    Milares, Luiz Paulo; Assis, Lívia; Siqueira, Amanda; Claudino, Vitoria; Domingos, Heloisa; Almeida, Thais; Tim, Carla; Renno, Ana Claudia

    2016-09-01

    The aim of this study was to evaluate the effects of an aquatic exercise program and low-level laser therapy (LLLT) (associated or not) on degenerative modifications and inflammatory mediators on the articular cartilage using an experimental model of knee OA. Forty male Wistar rats were divided into 4 groups: knee OA - without treatment (OA); OA plus exercise program group (OAE); OA plus LLLT (OAL); OA plus exercise program associated with LLLT (OAEL). Trained rats performed a water-jumping program carrying a load equivalent to 50-80 % of their body mass strapped to their chest. The laser irradiation was used either as the only method or after the exercise training had been performed, at 2 points contact mode (medial and lateral side of the left joint). The treatments started 4 weeks after the surgery, 3 days/week for 8 weeks. The results revealed that all treated groups (irradiated or not) exhibited a better pattern of tissue organization, with less fibrillation and irregularities along the articular surface and improved chondrocytes organization. Also, a lower cellular density and structural damage (OARSI score) and higher thickness values were observed in all treated groups. Additionally, OAE and OAEL showed a reduced expression in IL-1β and caspase-3 as compared with OA. Furthermore, a statistically lower MMP-13 expression was only observed in OAEL as compared with OA. These results suggest that aquatic exercise program and LLLT were effective in preventing cartilage degeneration. Also, physical exercise program presented anti-inflammatory effects in the knees in OA rats.

  6. Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide Cartilage Boundary Lubrication.

    Science.gov (United States)

    Abubacker, Saleem; Dorosz, Samuel G; Ponjevic, Dragana; Jay, Gregory D; Matyas, John R; Schmidt, Tannin A

    2016-04-01

    Proteoglycan 4 (PRG4) is a mucin-like glycoprotein present in synovial fluid and at the surface of articular cartilage. The objectives of this study were to (1) assess the articular cartilage surface adsorption and in vitro cartilage boundary lubricating ability of full-length recombinant human PRG4 (rhPRG4), and (2) cartilage boundary lubricating ability of purified rhPRG4, both alone and in combination with hyaluronan (HA). rhPRG4 adsorption onto articular cartilage explants was assessed by immunohistochemistry and dot blot. An in vitro cartilage-cartilage friction test was used to assess rhPRG4's cartilage boundary lubricating ability compared to bovine PRG4, and that of purified rhPRG4 both alone and in combination with HA. rhPRG4 was able to adsorb to the articular surface, as well as the cut surface, of cartilage explants. The kinetic coefficient of friction of rhPRG4 was similar to that of PRG4 (p = 0.16) and lower than phosphate-buffered saline (p < 0.05), while that of purified rhPRG4 + HA was significantly lower than rhPRG4 alone (p < 0.05). This study demonstrates that rhPRG4 can adsorb to an intact articular cartilage surface and functions as an effective boundary lubricant, both alone and with HA, and provides the foundation for in vivo evaluation of this clinically relevant full-length rhPRG4 for treatment of osteoarthritis.

  7. Comparative digital cartilage histology for human and common osteoarthritis models

    Directory of Open Access Journals (Sweden)

    Pedersen DR

    2013-02-01

    Full Text Available Douglas R Pedersen, Jessica E Goetz, Gail L Kurriger, James A MartinDepartment of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, USAPurpose: This study addresses the species-specific and site-specific details of weight-bearing articular cartilage zone depths and chondrocyte distributions among humans and common osteoarthritis (OA animal models using contemporary digital imaging tools. Histological analysis is the gold-standard research tool for evaluating cartilage health, OA severity, and treatment efficacy. Historically, evaluations were made by expert analysts. However, state-of-the-art tools have been developed that allow for digitization of entire histological sections for computer-aided analysis. Large volumes of common digital cartilage metrics directly complement elucidation of trends in OA inducement and concomitant potential treatments.Materials and methods: Sixteen fresh human knees, 26 adult New Zealand rabbit stifles, and 104 bovine lateral plateaus were measured for four cartilage zones and the cell densities within each zone. Each knee was divided into four weight-bearing sites: the medial and lateral plateaus and femoral condyles.Results: One-way analysis of variance followed by pairwise multiple comparisons (Holm–Sidak method at a significance of 0.05 clearly confirmed the variability between cartilage depths at each site, between sites in the same species, and between weight-bearing articular cartilage definitions in different species.Conclusion: The present study clearly demonstrates multisite, multispecies differences in normal weight-bearing articular cartilage, which can be objectively quantified by a common digital histology imaging technique. The clear site-specific differences in normal cartilage must be taken into consideration when characterizing the pathoetiology of OA models. Together, these provide a path to consistently analyze the volume and variety of histologic slides necessarily generated

  8. Reduced articular cartilage thickness in joints without a history of active arthritis in children with juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Pradsgaard, Dan Østergaard; Spannow, Anne Helene; Heuck, Carsten

    /217). Linear regression analyzes were controlled for age, gender, subtype, and adjusted for clustered data (right/left extremities). Results: We found a significantly thicker cartilage in healthy children than in the healthy joints of JIA children: Knee joint: mean (95% CI), 1.06 mm (0.77-1.36 mm, p... in joint cartilage thickness (Cth) between healthy children and JIA children measured by US (1). But are there any differences in Cth measured by US between healthy children and joints without a history of activity among JIA children’s. Aim: To investigate a possible effect of the inflammatory process...... on joints never directly affected by arthritic activity during the history of the child’s disease course. Furthermore we wanted to compare joint cartilage thickness within the JIA group in joints with or without a history of activity. Methods: We included 95 Danish JIA children. Age, mean (range) 10...

  9. O gel de plasma rico em plaquetas propicia a regeneração da cartilagem articular do joelho de ovelhas Platelet-rich plasma gel promotes regeneration of articular cartilage in knees of sheeps

    Directory of Open Access Journals (Sweden)

    Márcio de Oliveira Carneiro

    2013-04-01

    Full Text Available OBJETIVO: Avaliar a regeneração da cartilagem articular em defeitos osteocondrais do joelho induzidos pelo plasma rico em plaquetas (PRP autógeno. MÉTODOS: Defeitos osteocondrais produzidos no sulco troclear de ambos os joelhos de dez ovelhas foram preenchidos com PRP autógeno à direita e deixados vazios à esquerda. Avaliação macroscópica e histológica foram efetuadas 12 semanas mais tarde. Os resultados foram avaliados por um escore geral de ambas as avaliações macroscópica e histológica comparativamente entre os lados por meio do teste pareado de Wilcoxon. RESULTADOS: o aspecto macroscópico não foi uniforme entre os animais, nem diferiu entre os joelhos direitos e esquerdos (p=0,03125; em nenhum caso o tecido regenerado se nivelou com a cartilagem normal circundante. Ao exame histológico, cartilagem aparentemente normal não foi detectada em nenhum joelho, mas uma cartilagem pouco diferenciada estava presente em sete joelhos direitos e em três joelhos esquerdos. Tecido fibrocartilaginoso estava presente nos joelhos restantes, com diferença significante no escore geral entre os joelhos direitos e esquerdos (p=0,0313. CONCLUSÃO: o PRP como usado neste estudo tem propriedades reparativas da cartilagem articular no joelho de ovelhas, principalmente por estimular a formação de tecido fibrocartilaginoso. Trabalho Experimental.OBJECTIVE: to assess the regeneration of osteochondral defects in the joint cartilage of the knee induced by autologous platelet-rich plasma (pRp. METHODS: osteochondral defects produced in the trochlear groove of both knees of ten sheep; defects of the right knees were filled with autologous pRp and the left knees were left unfilled. macroscopic and microscopic evaluation was carried out 12 week later. the results were evaluated by the total score of both macroscopic and microscopic evaluations comparing the two sides through the wilcoxon paired test. RESULTS: macroscopic appearance was not uniform among

  10. Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2.

    Directory of Open Access Journals (Sweden)

    Alexander J Neumann

    Full Text Available Articular cartilage progenitor cells (ACPCs represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs. This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2. hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1 concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase. To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs

  11. Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model.

    Science.gov (United States)

    Kazemi, Davoud; Fakhrjou, Ashraf

    2015-10-01

    Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method. The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model. Eighteen adult Iranian mixed breed male dogs were used to conduct this experimental study. Full thickness articular cartilage defects (diameter 6 mm, depth 5 mm) were created in the weight bearing area of femoral condyles of both hind limbs in all dogs (n = 72). Twelve dogs were randomly selected to receive treatment and their right and left hind limb defects were treated by L-PRP and L-PRF implantation respectively, while no treatment was undertaken in six other dogs as controls. The animals were euthanized at 4, 16 and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. At each sampling time, 4 treated dogs and 2 control dogs were euthanized, therefore 8 defects per group were evaluated. Mean macroscopic scores of the treated defects were higher than the controls at all sampling times with significant differences (P L-PRF treated and control defects (10.13 vs. 8.37) and L-PRP treated and control defects (10 vs. 8.5) at 4 and 16 weeks, respectively. A similar trend in mean total microscopic scores was observed with a significant difference (P L-PRF could be used to effectively promote the healing of articular cartilage defects of the knee.

  12. Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation

    Directory of Open Access Journals (Sweden)

    James K. Hoffman

    2015-01-01

    Full Text Available Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.

  13. Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage.

    Science.gov (United States)

    Blain, Emma J; Ali, Ahmed Y; Duance, Victor C

    2010-06-01

    The aim of this study was to assess the anti-inflammatory efficacy of Boswellia frereana extracts in an in vitro model of cartilage degeneration and determine its potential as a therapy for treating osteoarthritis. Cartilage degradation was induced in vitro by treating explants with 5 ng/ml interleukin1alpha (IL-1alpha) and 10 ng/ml oncostatin M (OSM) over a 28-day period, in the presence or absence of 100 microg/ml B. frereana. Treatment of IL-1alpha/OSM stimulated cartilage explants with B. frereana inhibited the breakdown of the collagenous matrix. B. frereana reduced MMP9 and MMP13 mRNA levels, inhibited MMP9 expression and activation, and significantly reduced the production of nitrite (stable end product of nitric oxide), prostaglandin E2 and cycloxygenase-2. Epi-lupeol was identified as the principal constituent of B. frereana. This is the first report on the novel anti-inflammatory properties of Boswellia frereana in an in vitro model of cartilage degradation. We have demonstrated that B. frereana prevents collagen degradation, and inhibits the production of pro-inflammatory mediators and MMPs. Due to its efficacy we propose that B. frereana should be examined further as a potential therapeutic agent for treating inflammatory symptoms associated with arthritis. (c) 2009 John Wiley & Sons, Ltd.

  14. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  15. Origin and function of cartilage stem/progenitor cells in osteoarthritis.

    Science.gov (United States)

    Jiang, Yangzi; Tuan, Rocky S

    2015-04-01

    Articular cartilage is a physiologically non-self-renewing avascular tissue with a singular cell type, the chondrocyte, which functions as the load-bearing surface of the arthrodial joint. Injury to cartilage often progresses spatiotemporally from the articular surface to the subchondral bone, leading to development of degenerative joint diseases such as osteoarthritis (OA). Although lacking intrinsic reparative ability, articular cartilage has been shown to contain a population of stem cells or progenitor cells, similar to those found in many other adult tissues, that are thought to be involved in the maintenance of tissue homeostasis. These so-called cartilage-derived stem/progenitor cells (CSPCs) have been observed in human, equine and bovine articular cartilage, and have been identified, isolated and characterized on the basis of expression of stem-cell-related surface markers, clonogenicity and multilineage differentiation ability. However, the origin and functions of CSPCs are incompletely understood. We review here the current status of CSPC research and discuss the possible origin of these cells, what role they might have in cartilage repair, and their therapeutic potential in OA.

  16. Comparison of T1rho and T2 mapping of knee articular cartilage in an asymptomatic population

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Min A; Hong, Suk Joo; Im, A Lan [Dept. of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Kang, Chang Ho [Dept. of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Baek Hyun [Dept. of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan (Korea, Republic of); Kim, In Seong [Siemens Healthcare, Seoul (Korea, Republic of)

    2016-11-15

    To analyze subregional differences in T1rho (T1ρ) and T2 values and their correlation in asymptomatic knee cartilage, and to evaluate angular dependence with magic angles. Six asymptomatic volunteers underwent knee MRI with T1ρ and T2 mapping. T1ρ and T2 values were measured by two radiologists independently, at nine subregions in the medial femoral condyle (MFC) cartilage, at angles of ± 0°, 15°, 35°, 55°, 75° respective to a vertical line (B0) bisecting the width of the distal femur, and at two locations in the patella. Subregional values of T1ρ and T2 were analyzed and significant differences in three divided portions of the MFC (anterior, central, and posterior) were statistically evaluated. Correlation between T1ρ and T2 and angular dependence with magic angles were also assessed for statistical significance. T1ρ values were lowest at +15° and highest at -55°. T2 values were lowest at +75° and highest at +35°. Both T1ρ and T2 were higher in superior patella than inferior patella. T1ρ showed significant differences in the three divided portions of the MFC, while T2 showed significant differences only between central and posterior portions. There was a weak correlation between T1ρ and T2 (r = 0.217, p = 0.127). T1ρ showed more angular dependence than T2. T1ρ and T2 showed different subregional values and angular dependence in asymptomatic knee cartilage with a weak correlation. Awareness of these differences will aid in assessment of cartilage in a specific subregion of the knee.

  17. Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

    DEFF Research Database (Denmark)

    Wang, Bijue; Chen, Pingping; Jensen, Anne-Christine Bay

    2009-01-01

    -epitope specific immunoassays; (1) sandwich (342)FFGVG-G2 ELISA, (2) competition NITEGE(373)ELISA (3) sandwich G1-NITEGE(373 )ELISA (4) competition (374)ARGSV ELISA, and (5) sandwich (374)ARGSV-G2 ELISA all detecting aggrecan fragments, and (6) sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen......- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. FINDINGS: Bovine cartilage explants were....... We found that (1) aggrecanase-derived aggrecan fragments are released in the early (day 2-7) and mid phase (day 9-14) into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2) the release of NITEGE(373 )neo-epitopes are delayed compared to the corresponding (374...

  18. Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics

    DEFF Research Database (Denmark)

    Ye, Fengbin; Baldursdottir, Stefania; Hvidt, Søren

    2016-01-01

    /v) chondroitin sulfate or 0.5% (w/v) hyaluronic acid were developed, and their rheological and morphological properties were characterized. UV imaging was utilized to quantify the transport properties of the following four model compounds in the agarose gel and in the developed artificial cartilage models: H......-Ala-β-naphthylamide, H-Lys-Lys-β-naphthylamide, lysozyme, and α-lactalbumin. The obtained results showed that the incorporation of the polyelectrolytes chondroitin sulfate or hyaluronic acid into agarose gel induced a significant reduction in the apparent diffusivities of the cationic model compounds as compared...

  19. Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

    2016-03-01

    Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

  20. Advances in cartilage tissue engineering : in vitro

    NARCIS (Netherlands)

    E.W. Mandl (Erik)

    2004-01-01

    textabstractWithin the body three subtypes of cartilage can be distinguished: hyaline cartilage, elastic cartilage and fibrocartilage. Hyaline cartilage is the predominant subtype and is mainly located in articular joints and in less extent in the nasal septum and cricoid. Elastic cartilage can be

  1. Sulfato de condroitina e hialuronato de sódio no tratamento da doença articular degenerativa em cães: estudo histológico da cartilagem articular e membrana sinovial Chondroitin sulfate and sodium hyaluronate in the treatment of the degenerative joint disease in dogs: histological features of articular cartilage and synovium

    Directory of Open Access Journals (Sweden)

    E.G. Melo

    2008-02-01

    processo degenerativo da cartilagem articular. Não foi constatada ação favorável das drogas na membrana sinovial.Fifteen mongrel dogs, both genders, weighting from 18 to 25kg were used and Degenerative Joint Disease (DJD was induced through cranial cruciate ligament (CCrL artroscopical section. After three weeks, CCrL was reconstructed by Schawalder's (1989 technique. Then, dogs were distributed in three groups and the following protocols were used: group I, control, no other treatment but the CCrL reconstruction; group II received chondroitin sulfate 24mg per animal every five days, intramuscularly, in a total of six injections; and group III received sodium hyaluronate 20mg per animal every five days, intravenously, in a total of three injections. Clinical observation was done until 90 days after treatments. By that time, the articular cartilage and synovium were collected and their morphology was evaluated. In group I, the degenerative alterations of the DJD were the most intense. Thus, decrease of chondrocytes number, pannus, fibrillations, grooves, erosion, and irregular articular surface were observed on the cartilage. In group II, raise of chondrocytes number was observed, with increase of synthesis activity of matrix and decrease of lesions on the articular surface. There was an increase of chondrocytes in group III, but the cells were morphologically unviable. All the groups showed proliferation of the synovial membrane, with limpho-plasma cells infiltrated in subintim and perivascular. In groups I and III, the proliferation of synovium was abundant, with formation of pannus, flattened synoviocytes or synovium absent with granulation tissue. Those results suggest that the chondroitin sulfate stimulated the articular cartilage; decreasing or delaying the alterations of DJD, as well as, the sodium hyaluronate did not interfere on degenerative process in articular cartilage. No favorable action of these drugs in the synovial membrane was verified.

  2. Cartilage Engineering and Microgravity

    Science.gov (United States)

    Toffanin, R.; Bader, A.; Cogoli, A.; Carda, C.; Fantazzini, P.; Garrido, L.; Gomez, S.; Hall, L.; Martin, I.; Murano, E.; Poncelet, D.; Pörtner, R.; Hoffmann, F.; Roekaerts, D.; Ronney, P.; Triebel, W.; Tummers, M.

    2005-06-01

    The complex effects of mechanical forces and growth factors on articular cartilage development still need to be investigated in order to identify optimal conditions for articular cartilage repair. Strictly controlled in vitro studies under modelled or space microgravity conditions can improve our understanding of the fundamental role of gravity in articular cartilage development. The main objective of this Topical Team is to use modelled microgravity as a tool to elucidate the fundamental science of cartilage regeneration. Particular attention is, therefore, given to the effects of physical forces under altered gravitational conditions, applied using controlled bioreactor systems, on cell metabolism, cell differentiation and tissue development. Specific attention is also directed toward the potential advantages of using magnetic resonance methods for the non-destructive characterisation of scaffolds, chondrocytes-polymer constructs and tissue engineered cartilage.

  3. Return to sport after the surgical management of articular cartilage lesions in the knee: a meta-analysis.

    Science.gov (United States)

    Krych, Aaron J; Pareek, Ayoosh; King, Alexander H; Johnson, Nick R; Stuart, Michael J; Williams, Riley J

    2017-10-01

    Optimal surgical treatment of chondral defects in an athletic population remains highly controversial and has yet to be determined. The purpose of this review was to (1) report data on return to sport and (2) compare activity and functional outcome measures following various cartilage restoration techniques. A comprehensive review was performed for studies with return-to-sport outcomes after microfracture (MFX), osteochondral autograft transfer (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI). All studies containing return-to-sport participation with minimum 2-year post-operative activity-based outcomes were included. A meta-analysis comparing rate of return to sport between each surgical intervention was conducted using a random-effects model. Forty-four studies met inclusion criteria (18 Level I/II, 26 Level III/IV). In total, 2549 patients were included (1756 M, 793 F) with an average age of 35 years and follow-up of 47 months. Return to sport at some level was 76 % overall, with highest rates of return after OAT (93 %), followed by OCA (88 %), ACI (82 %), and MFX (58 %). Osteochondral autograft transfer showed the fastest return to sports (5.2 ± 1.8 months) compared to 9.1 ± 2.2 months for MFX, 9.6 ± 3.0 months for OCA and 11.8 ± 3.8 months for ACI (P sport. In conclusion, in this meta-analysis of 2549 athletes, cartilage restoration surgery had a 76 % return to sport at mid-term follow-up. Osteochondral autograft transfer offered a faster recovery and appeared to have a higher rate of return to preinjury athletics, but heterogeneity in lesion size, athlete age, and concomitant surgical procedures are important factors to consider when assessing individual athletes. This study reports on the rate of return to sport in athletes undergoing various procedures for symptomatic chondral defects. IV.

  4. Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering

    OpenAIRE

    Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G.; Ching, Kuan Y.; Jonnalagadda, Umesh S.; Oreffo, Richard O.C.; Hill, Martyn; Tare, Rahul S.

    2014-01-01

    Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-bu...

  5. Concentration determination of collagen and proteoglycan in bovine nasal cartilage by Fourier transform infrared imaging and PLS

    Science.gov (United States)

    Zhang, Xuexi; Xiao, Zhi-Yan; Yin, Jianhua; Xia, Yang

    2014-09-01

    Fourier transform infrared imaging (FTIRI) combined with chemometrics can be used to detect the structure of bio-macromolecule, measure the concentrations of some components, and so on. In this study, FTIRI with Partial Least-Squares (PLS) regression was applied to study the concentration of two main components in bovine nasal cartilage (BNC), collagen and proteoglycan. An infrared spectrum library was built by mixing the collagen and chondroitin 6-sulfate (main of proteoglycan) at different ratios. Some pretreatments are needed for building PLS model. FTIR images were collected from BNC sections at 6.25μm and 25μm pixel size. The spectra extracted from BNC-FTIR images were imported into the PLS regression program to predict the concentrations of collagen and proteoglycan. These PLS-determined concentrations are agreed with the result in our previous work and biochemical analytical results. The prediction shows that the concentrations of collagen and proteoglycan in BNC are comparative on the whole. However, the concentration of proteoglycan is a litter higher than that of collagen, to some extent.

  6. Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the Superficial Zone of the Human Articular Cartilage and Changes in Surface Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.

    Science.gov (United States)

    Kiyan, Wataru; Ito, Akira; Nakagawa, Yasuaki; Mukai, Shogo; Mori, Koji; Arai, Tatsuo; Uchino, Eiichiro; Okuno, Yasushi; Kuroki, Hiroshi

    2017-08-01

    We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (R q ), average collagen content (A 1 ) and collagen orientation (A 12 ) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (R c ) had a significant coefficient of determination with R q and A 12 (R LMMm 2 =0.79); however, R c did not correlate with A 1 . Concerning the collagen characteristic in the superficial zone, R c was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. Infrapatellar fat pad aggravates degeneration of acute traumatized cartilage: a possible role for interleukin-6.

    Science.gov (United States)

    He, J; Jiang, Y; Alexander, P G; Ulici, V; Zhu, Y; Wu, S; Tuan, R S

    2017-01-01

    The infrapatellar fat pad (IPFP), which is located underneath the patella, close to cartilage surfaces, functions in distributing mechanical load and has been shown to produce cytokines. This study aims to assess the involvement of the IPFP in the progression of post-traumatic osteoarthritis (OA) through investigating the crosstalk between the IPFP and injured cartilage in vitro. A single blunt impact (36 MPa) on healthy bovine articular cartilage explants was used to generate traumatized cartilage. Conditioned media from IPFP and traumatized cartilage (FP-CM and TC-CM) were prepared separately. After culturing in FP-CM, the posttraumatic cartilage explants were analyzed for expression of cartilage degeneration associated genes and secretion of the interleukin (IL)-6, into the culture medium. The effect of traumatized cartilage on IPFP was studied by treating IPFP-derived adipocytes and IPFP adipose-derived stromal cells (ADSC) with TC-CM followed by analysis of cytokine expression. FP-CM aggravated glycosaminoglycan (GAG) release in traumatized cartilage, but did not significantly affect healthy cartilage. FP-CM raised gene expression of cyclooxygenase-2, inducible nitric oxide synthase, and IL-6 in traumatized cartilage explants, and lowered expression of tissue inhibitor of metalloproteinases-1, 2, 3, compared to non-conditioned medium. Of particular significance is that medium IL-6 levels increased substantially in both FP-CM and FP-CM treated traumatized cartilage cultures. Extrinsic IL-6 treatment of traumatized cartilage simulated part of the effects of FP-CM. TC-CM elevated levels of IL-6 expression in IPFP derived adipocytes and ADSCs. IPFP aggravates post-traumatized cartilage degeneration, and IL-6 is a candidate tissue degeneration mediator. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Sonography on injury of the medial patellofemoral ligament after acute traumatic lateral patellar dislocation: Injury patterns and correlation analysis with injury of articular cartilage of the inferomedial patella.

    Science.gov (United States)

    Zhang, Guang-Ying; Zheng, Lei; Shi, Hao; Qu, Su-Hui; Ding, Hong-Yu

    2013-12-01

    The purpose of this study was to investigate the accuracy of high-frequency ultrasonography in the diagnosis of injuries of medial patellofemoral ligaments (MPFLs), analyse the characteristics of MPFL injury and correlations between injury of the MPFL and articular cartilage of the inferomedial patella in patients with acute traumatic lateral patellar dislocation. High-frequency sonographic images of 49 patients with acute traumatic lateral patellar dislocations treated surgically were reviewed. The χ(2) tests were performed for statistical analysis. Twenty-eight cases of complete MPFL tear and 21 cases of partial MPFL tear were identified in operation, with 27 cases of MPFL tear located at their femoral attachment, 21 cases of tear at the patellar attachment and one case of midsubstance tear. The diagnostic accuracy of sonography regarding partial MPFL tear and complete MPFL tear was 89.8% and 89.8%. Among the patients with MPFL tear at the patellar attachment, eight and six cases were concomitant with chondral and osteochondral lesions in the inferomedial patella, respectively, in contrast to nine and six cases in patients with MPFL tear at the femoral attachment, respectively. There was no significant difference between the two locations described above regarding the prevalence rates of chondral or osteochondral lesions of the inferomedial patella (P=0.732, P=0.614). Among the patients with complete MPFL tear, 12 and 10 cases were concomitant with chondral and osteochondral lesions in the inferomedial patella, respectively, while six and two cases were concomitant with partial MPFL tear. There was no significant difference between the two types of injuries discussed above on the prevalence rates of chondral lesions of the inferomedial patella (P=0.305), but the prevalence rate of osteochondral lesions between the two types of injuries discussed above was statistically different (P=0.035). The MPFL is most easily injured at the femoral attachment, secondly at

  9. Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

    Directory of Open Access Journals (Sweden)

    Sakari S. Karhula

    2017-08-01

    Full Text Available Contrast-enhanced micro-computed tomography (CEμCT with cationic and anionic contrast agents reveals glycosaminoglycan (GAG content and distribution in articular cartilage (AC. The advantage of using cationic stains (e.g., CA4+ compared to anionic stains (e.g., Hexabrix®, is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution μCT setups. In this study, we use high-resolution μCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo μCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml and imaged with high-resolution μCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis

  10. Micro-Scale Distribution of CA4+ in Ex Vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

    Science.gov (United States)

    Karhula, Sakari S.; Finnilä, Mikko A.; Freedman, Jonathan D.; Kauppinen, Sami; Valkealahti, Maarit; Lehenkari, Petri; Pritzker, Kenneth P. H.; Nieminen, Heikki J.; Snyder, Brian D.; Grinstaff, Mark W.; Saarakkala, Simo

    2017-08-01

    Contrast-enhanced micro-computed tomography (CEµCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g. CA4+) compared to anionic stains (e.g. Hexabrix®), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution µCT setups. In this study, we use high-resolution µCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo µCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6mgI/ml, and 24 mgI/ml) and imaged with high-resolution µCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples

  11. Cartilage Tissue Engineering: the effect of different biomaterials, cell types and culture methods

    NARCIS (Netherlands)

    W.J.C.M. Marijnissen (Willem)

    2006-01-01

    textabstractChapter 1 outlines the normal structure and composition of articular cartilage and the inefficient spontaneous healing response after focal damage. Current surgical treatment options are briefly discussed and tissue engineering techniques for the repair of articular cartilage defects

  12. Associations of three-dimensional T1 rho MR mapping and three-dimensional T2 mapping with macroscopic and histologic grading as a biomarker for early articular degeneration of knee cartilage.

    Science.gov (United States)

    Sasho, T; Katsuragi, J; Yamaguchi, S; Haneishi, H; Aizimu, T; Tanaka, T; Watanabe, A; Sato, Y; Akagi, R; Matsumoto, K; Uno, T; Motoori, K

    2017-04-29

    T1 rho and T2 mapping are magnetic resonance imaging (MRI) techniques to detect early degenerative changes in cartilage. Recent advancements have enabled 3D acquisition for both techniques. The objective of the present study was to examine the correlation of 3D T1 rho and 3D T2 mapping with macroscopic and histological characteristics of knee cartilage. Twenty-one patients who underwent total knee arthroplasty due to osteoarthritis with involvement of the medial compartment but with minimum involvement of the lateral compartment were enrolled. Prior to surgery, five series of MRI were acquired with a 3-T scanner. 3D T1 rho/T2 analyses were performed following determination of regions to be assessed using in-house software that incorporated three series of MRI acquisitions data (3D-MERGE, 3D-SPGR, and 3D-CUBE). During surgery, the cartilage of the lateral compartment was macroscopically assessed with the International Cartilage Research Society (ICRS) articular classification system. The extracted specimens were histologically assessed using the OARSI histology score. Three regions of interest (ROI) were assessed for each slice (two slices per knee): the central lateral femoral condyle (cLFC), the posterior portion of the lateral femoral condyle (pLFC), and the lateral tibia plateau (LTP). For each ROI, the mean T1 rho and T2 relaxation time, the ICRS grade, and the OARSI score were compared. Neither the T1 rho nor the T2 reflected the macroscopic grading. The T1 rho could discriminate between histological grades 1 and 2. However, the T2 could not. The T1 rho relaxation time was higher in the pLFC than in the cLFC even in the same grade. Compared to T2 mapping, T1 rho mapping may have an advantage in differentiating grades I and II cartilage degeneration on OARSI histological grading system.

  13. Professional ballet dancers have a similar prevalence of articular cartilage defects compared to age- and sex-matched non-dancing athletes.

    Science.gov (United States)

    Mayes, Susan; Ferris, April-Rose; Smith, Peter; Garnham, Andrew; Cook, Jill

    2016-12-01

    Ballet exposes the hip joint to repetitive loading in extreme ranges of movement and may predispose a dancer to pain and osteoarthritis (OA). The aims of this study were to compare the prevalence of cartilage defects in professional ballet dancers and athletes and to determine the relationship of clinical signs and symptoms. Forty-nine male and female, current and retired professional ballet dancers and 49 age- and sex-matched non-dancing athletes completed hip pain questionnaires, including the Copenhagen Hip and Groin Outcome Score (HAGOS), and underwent hip range of movement (ROM) testing and 3-Tesla magnetic resonance imaging to score cartilage defects (no defect, grade 1: focal partial defect and grade 2: diffuse or full thickness defect). Thirty (61 %) dancers and 27 (55 %) athletes had cartilage defects (p = 0.54). The frequency of grade 1 and 2 cartilage defects did not differ between dancers and athletes (p = 0.83). The frequency of cartilage defects was similar in male and female dancers (p = 0.34), and male and female athletes (p = 0.24). Cartilage defects were not related to history of hip pain (p = 0.34), HAGOS pain (p = 0.14), sports/rec (p = 0.15) scores or hip internal rotation ≤20° (p > 0.01). Cartilage defects were related to age in male dancers (p = 0.002). Ballet dancers do not appear to be at a greater risk of cartilage injury compared to non-dancing athletes. Male dancers develop cartilage defects at an earlier age than athletes and female dancers. Cartilage defects were not related to clinical signs and symptoms; thus, prospective studies are required to determine which cartilage defects progress to symptomatic hip OA.

  14. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Total joint prosthesis is commonly made with a metal component articulating against a component of ultrahigh molecular weight polyethylene (to be referred to as UHMWPE). Ultra-high molecular weight polyethylene. (UHMWPE) has been choice of orthopaedic bearing material in total joint replacement surgery since 1962 ...

  15. Effects of different mode high-intensity movement training on articular cartilage in histology - a randomised controlled trial on rabbit knee

    Directory of Open Access Journals (Sweden)

    Ch Qi

    2008-12-01

    Full Text Available Objective: To study the “starting mechanism” and pathological process of knee cartilage injury in different movement training with high intensity. Materials and Methods: 72 New Zealand white rabbits we