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Sample records for rapid bone formation

  1. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2008-02-01

    length from the tibial fusion site, and then stop which would be consistent with the resorption being associated with the lack of weight bearing load. In...Defect in the Rat Femur with Use of a Vascularized Periosteal Flap, a Biodegradable Matric, and Bone Morphogenetic Protein. J Bone Joint Surg 87-A(6

  2. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2012-03-01

    osteoinductive components that could be seeded into the osteoconductive materials to generate normal bone which this study will explore. The central...without a scaffold, by using cells transduced with adenovirus vectors to express an osteoinductive factor (BMP2), which have been encapsulated in...minimally invasive percutaneous techniques and without a scaffold, by using cells transduced with adenovirus vectors to express an osteoinductive factor

  3. Hydrothermal Synthesis of Hydroxyapatite Nanorods for Rapid Formation of Bone-Like Mineralization

    Science.gov (United States)

    Hoai, Tran Thanh; Nga, Nguyen Kim; Giang, Luu Truong; Huy, Tran Quang; Tuan, Phan Nguyen Minh; Binh, Bui Thi Thanh

    2017-08-01

    Hydroxyapatite (HAp) is an excellent biomaterial for bone repair and regeneration. The biological functions of HAp particles, such as biomineralization, cell adhesion, and cell proliferation, can be enhanced when their size is reduced to the nanoscale. In this work, HAp nanoparticles were synthesized by the hydrothermal technique with addition of cetyltrimethylammonium bromide (CTAB). These particles were also characterized, and their size controlled by modifying the CTAB concentration and hydrothermal duration. The results show that most HAp nanoparticles were rod-like in shape, exhibiting the most uniform and smallest size (mean diameter and length of 39 nm and 125 nm, respectively) at optimal conditions of 0.64 g CTAB and hydrothermal duration of 12 h. Moreover, good biomineralization capability of the HAp nanorods was confirmed through in vitro tests in simulated body fluid. A bone-like mineral layer of synthesized HAp nanorods formed rapidly after 7 days. This study shows that highly bioactive HAp nanorods can be easily prepared by the hydrothermal method, being a potential nanomaterial for bone regeneration.

  4. Effects of strontium ranelate on bone formation in the mid-palatal suture after rapid maxillary expansion

    Directory of Open Access Journals (Sweden)

    Zhao SY

    2015-05-01

    Full Text Available Shuya Zhao,1,* Xuxia Wang,2,* Na Li,3 Yun Chen,1 Yuran Su,1 Jun Zhang1 1Department of Orthodontics, 2Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Shandong University; 3Department of Orthodontics, Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The aim of this experimental study was to investigate the effects of strontium ranelate on bone regeneration in the mid-palatal suture in response to rapid maxillary expansion (RME.Methods: Thirty-six male 6-week-old Wistar rats were randomly divided into three groups, ie, an expansion only (EO group, an expansion plus strontium ranelate (SE group, and a control group. An orthodontic appliance was set between the right and left upper molars of rats with an initial expansive force of 0.98 N. Rats in the SE group were administered strontium ranelate (600 mg/kg body weight and then euthanized in batches on days 4, 7, and 10. Morphological changes in the mid-palatal suture were investigated using micro-computed tomography and hematoxylin and eosin staining after RME. Bone morphogenetic protein-2 expression in the suture was also examined to evaluate bone formation in the mid-palatal suture. Image-Pro Plus software was then used to determine the mean optical density of the immunohistochemical images. Analysis of variance was used for statistical evaluation at the P<0.05 level.Results: With expansive force, the mid-palatal suture was expanded, but there was no statistically significant difference (P>0.05 between the SE and EO groups. The bone volume of the suture decreased after RME, but was higher in the SE group than in the EO group on days 7 and 10. Further, expression of bone morphogenetic protein-2 in the SE group was higher than in the other two groups (P<0.05.Conclusion: Strontium ranelate may hasten new bone formation in the expanded mid-palatal suture, which may be therapeutically

  5. Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform

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    Ugo Ripamonti

    2016-09-01

    Full Text Available The soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-β3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-β3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus. In marked contrast, the three mammalian TGF-βs do not initiate the induction of bone formation in rodents and lagomorphs. The induction of bone by hTGF-β3/preloaded bioreactors is orchestrated by inducing fibrin-fibronectin rings that structurally organize tissue patterning and morphogenesis within the macroporous spaces. Induced advancing extracellular matrix rings provide the structural anchorage for hyper chromatic cells, interpreted as differentiating osteoblasts re-programmed by hTGF-β3 from invading myoblastic and/or pericytic differentiated cells. Runx2 and Osteocalcin expression are significantly up-regulated correlating to multiple invading cells differentiating into the osteoblastic phenotype. Bioreactors pre-loaded with recombinant human Noggin (hNoggin, a BMPs antagonist, show down-regulation of BMP-2 and other profiled osteogenic proteins’ genes resulting in minimal bone formation. Coral-derived macroporous constructs preloaded with binary applications of hTGF-β3 and hNoggin also show down-regulation of BMP-2 with the induction of limited bone formation. The induction of bone formation by hTGF-β3 is via the BMPs pathway and it is thus blocked by hNoggin. Our systematic studies in Papio ursinus with translational hTGF-β3 in large cranio-mandibulo-facial defects in humans are now requesting the re-evaluation of Bone

  6. Simultaneous gene transfer of bone morphogenetic protein (BMP -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    Directory of Open Access Journals (Sweden)

    Miyazaki Jun-ichi

    2006-08-01

    Full Text Available Abstract Background Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. Methods First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. Results In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. Conclusion The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.

  7. Effects of low-level laser therapy on osteoblastic bone formation and relapse in an experimental rapid maxillary expansion model.

    Science.gov (United States)

    Aras, M H; Erkilic, S; Demir, T; Demirkol, M; Kaplan, D S; Yolcu, U

    2015-01-01

    The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on osteoblastic bone formation and relapse during expansion of rat palatal sutures. Thirty-two Wistar rats were randomly allocated into two groups of 16 rats each. In the first group, LLLT was applied 4 days after expansion commenced. Seven days after expansion, retainers were applied for 10 days. The second group was similarly treated, with the exception of laser therapy. All rats were sacrificed on day 7 (n = 1) (the end of the expansion period; laser group (LG) 1 [LLLT 1] and control group (CG) 1 [control 1]) and day 17 (n = 8) (the end of the retention period; LG 2 [LLLT 2] and CG 2 [control 2]) for histological assessment. The LLLT 1 group had significantly higher numbers of osteoclasts than did the control 1 group (P = 0.036). No significant between-group difference in osteoblast cell or capillary numbers was evident when day 7 and 17 data were compared. Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing.

  8. Ectopic bone formation in rapidly fabricated acellular injectable dense collagen-Bioglass hybrid scaffolds via gel aspiration-ejection.

    Science.gov (United States)

    Miri, Amir K; Muja, Naser; Kamranpour, Neysan O; Lepry, William C; Boccaccini, Aldo R; Clarke, Susan A; Nazhat, Showan N

    2016-04-01

    Gel aspiration-ejection (GAE) has recently been introduced as an effective technique for the rapid production of injectable dense collagen (IDC) gel scaffolds with tunable collagen fibrillar densities (CFDs) and microstructures. Herein, a GAE system was applied for the advanced production and delivery of IDC and IDC-Bioglass(®) (IDC-BG) hybrid gel scaffolds for potential bone tissue engineering applications. The efficacy of GAE in generating mineralizable IDC-BG gels (from an initial 75-25 collagen-BG ratio) produced through needle gauge numbers 8G (3.4 mm diameter and 6 wt% CFD) and 14G (1.6 mm diameter and 14 wt% CFD) was investigated. Second harmonic generation (SHG) imaging of as-made gels revealed an increase in collagen fibril alignment with needle gauge number. In vitro mineralization of IDC-BG gels was confirmed where carbonated hydroxyapatite was detected as early as day 1 in simulated body fluid, which progressively increased up to day 14. In vivo mineralization of, and host response to, acellular IDC and IDC-BG gel scaffolds were further investigated following subcutaneous injection in adult rats. Mineralization, neovascularization and cell infiltration into the scaffolds was enhanced by the addition of BG and at day 21 post injection, there was evidence of remodelling of granulation tissue into woven bone-like tissue in IDC-BG. SHG imaging of explanted scaffolds indicated collagen fibril remodelling through cell infiltration and mineralization over time. In sum, the results suggest that IDC-BG hybrid gels have osteoinductive properties and potentially offer a novel therapeutic approach for procedures requiring the injectable delivery of a malleable and dynamic bone graft that mineralizes under physiological conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Bone formation: roles of genistein and daidzein

    Science.gov (United States)

    Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

  10. Effect of the laser and light-emitting diode (LED) phototherapy on midpalatal suture bone formation after rapid maxilla expansion: a Raman spectroscopy analysis.

    Science.gov (United States)

    Rosa, Cristiane Becher; Habib, Fernando Antonio Lima; de Araújo, Telma Martins; Aragão, Juliana Silveira; Gomes, Rafael Soares; Barbosa, Artur Felipe Santos; Silveira, Landulfo; Pinheiro, Antonio L B

    2014-05-01

    The aim of this study was to analyze the effect of laser or light-emitting diode (LED) phototherapy on the bone formation at the midpalatal suture after rapid maxilla expansion. Twenty young adult male rats were divided into four groups with 8 days of experimental time: group 1, no treatment; group 2, expansion; group 3, expansion and laser irradiation; and group 4, expansion and LED irradiation. In groups 3 and 4, light irradiation was in the first, third, and fifth experimental days. In all groups, the expansion was accomplished with a helicoid 0.020" stainless steel orthodontic spring. A diode laser (λ780 nm, 70 mW, spot of 0.04 cm(2), t = 257 s, spatial average energy fluence (SAEF) of 18 J/cm(2)) or a LED (λ850 nm, 150 mW ± 10 mW, spot of 0.5 cm(2), t = 120 s, SAEF of 18 J/cm(2)) were used. The samples were analyzed by Raman spectroscopy carried out at midpalatal suture and at the cortical area close to the suture. Two Raman shifts were analyzed: ∼ 960 (phosphate hydroxyapatite) and ∼ 1,450 cm(-1) (lipids and protein). Data was submitted to statistical analysis. Significant statistical difference (p ≤ 0.05) was found in the hydroxyapatite (CHA) peaks among the expansion group and the expansion and laser or LED groups. The LED group presented higher mean peak values of CHA. No statistical differences were found between the treated groups as for collagen deposition, although LED also presented higher mean peak values. The results of this study using Raman spectral analysis indicate that laser and LED light irradiation improves deposition of CHA in the midpalatal suture after orthopedic expansion.

  11. New bone formation in the maxillary sinus without bone grafts.

    Science.gov (United States)

    Sohn, Dong-Seok; Lee, Ji-Soo; Ahn, Mi-Ra; Shin, Hong-In

    2008-09-01

    Various sinus augmentation procedures, using bone substitutes, have been used to place dental implants in the atrophic posterior maxilla. The aim of this article is to evaluate the possibility of new bone formation in the maxillary sinus without a bone graft. Ten patients without significant sinus pathosis were selected for this study. The bony window was prepared in the lateral wall using the ultrasonic piezoelectric bone surgery device (Surgybone, Silfradent srl, Sofia, Italy). The sinus membrane was elevated superiorly and implants were placed simultaneously to maintain the space under the sinus membrane for new bone formation. As the methods of sealing the lateral access window of the sinus, patients were divided into 2 groups. Nonresorbable membrane was used to seal the lateral access window of the maxillary sinus after implant placement in 5 cases (group A). Replaceable bony window was used to seal the lateral wall of the sinus in another 5 cases (group B). Computed tomograms were taken immediately before and after surgery, at the uncovering of the implant, and after a 6 month healing period. A bone biopsy was taken on the previous bony window area to evaluate new bone formation. A total of 21 implants in lengths of 10 to 15 mm (mean, 13 mm) were placed, with an average residual bone height of 5 mm (range, 1-9 mm). All implants remained stable during the study period in clinical evaluations. New bone formation and new sinus floors were found in radiographic and histologic evaluations. The human study showed the capacity of new bone formation in the maxillary sinus with membrane elevation only and simultaneous implant placement beyond the original sinus floor. New bone formation without additional bone graft in the maxillary sinus is revealed from the clinical, radiographic, and histologic results, but furthermore long-term studies are needed to confirm this.

  12. Lutein Enhances Bone Mass by Stimulating Bone Formation and Suppressing Bone Resorption in Growing Mice.

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    Takeda, Hiroshi; Tominari, Tsukasa; Hirata, Michiko; Watanabe, Kenta; Matsumoto, Chiho; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

    2017-01-01

    Lutein is a member of the xanthophyll family of carotenoids, which are known to prevent hypoxia-induced cell damage in the eye by removing free radicals. However, its role in other tissues is controversial, and the effects of lutein on bone tissues are unknown. To identify a possible role of lutein in bone tissues, we examined the effects of lutein on bone formation and bone resorption and on femoral bone mass in mice. Lutein enhanced the formation of mineralized bone nodules in cultures of osteoblasts. On the other hand, lutein clearly suppressed 1α, 25-dihydroxyvitamin D 3 -induced bone resorption as measured by pit formation in organ culture of mouse calvaria. In co-cultures of bone marrow cells and osteoblasts, lutein suppressed 1α, 25-dihydroxyvitamin D 3 -induced osteoclast formation. In cultures of bone marrow macrophages, lutein suppressed soluble RANKL, the receptor activator of nuclear factor-kappaB (NF-κB) ligand, induced osteoclast formation. When five-week-old male mice were orally administered lutein for 4 weeks, the femoral bone mass was clearly enhanced in cortical bone, as measured by bone mineral density in dual X-ray absorptiometry and micro computed tomography (µCT) analyses. The present study indicates that lutein enhances bone mass in growing mice by suppressing bone resorption and stimulating bone formation. Lutein may be a natural agent that promotes bone turnover and may be beneficial for bone health in humans.

  13. Understanding coupling between bone resorption and formation

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Abdelgawad, Mohamed Essameldim; Kristensen, Helene Bjørg

    2013-01-01

    Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing...... these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined...... histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested...

  14. Local induction of inflammation affects bone formation

    NARCIS (Netherlands)

    Croes, M.|info:eu-repo/dai/nl/413641902; Kruyt, M. C.|info:eu-repo/dai/nl/258751606; Loozen, L.; Kragten, A. H M; Yuan, H.; Dhert, W. J.; Öner, F. C.|info:eu-repo/dai/nl/188615326; Alblas, Jacqueline|info:eu-repo/dai/nl/147759234

    2017-01-01

    To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of

  15. Alveolar bone changes after asymmetric rapid maxillary expansion.

    Science.gov (United States)

    Akin, Mehmet; Baka, Zeliha Muge; Ileri, Zehra; Basciftci, Faruk Ayhan

    2015-09-01

    To quantitatively evaluate the effects of asymmetric rapid maxillary expansion (ARME) on cortical bone thickness and buccal alveolar bone height (BABH), and to determine the formation of dehiscence and fenestration in the alveolar bone surrounding the posterior teeth, using cone-beam computed tomography (CBCT). The CBCT records of 23 patients with true unilateral posterior skeletal crossbite (10 boys, 14.06 ± 1.08 years old, and 13 girls, 13.64 ± 1.32 years old) who had undergone ARME were selected from our clinic archives. The bonded acrylic ARME appliance, including an occlusal stopper, was used on all patients. CBCT records had been taken before ARME (T1) and after the 3-month retention period (T2). Axial slices of the CBCT images at 3 vertical levels were used to evaluate the buccal and palatal aspects of the canines, first and second premolars, and first molars. Paired samples and independent sample t-tests were used for statistical comparison. The results suggest that buccal cortical bone thickness of the affected side was significantly more affected by the expansion than was the unaffected side (P ARME significantly reduced the BABH of the canines (P ARME also increased the incidence of dehiscence and fenestration on the affected side. ARME may quantitatively decrease buccal cortical bone thickness and height on the affected side.

  16. Rapid gas hydrate formation process

    Science.gov (United States)

    Brown, Thomas D.; Taylor, Charles E.; Unione, Alfred J.

    2013-01-15

    The disclosure provides a method and apparatus for forming gas hydrates from a two-phase mixture of water and a hydrate forming gas. The two-phase mixture is created in a mixing zone which may be wholly included within the body of a spray nozzle. The two-phase mixture is subsequently sprayed into a reaction zone, where the reaction zone is under pressure and temperature conditions suitable for formation of the gas hydrate. The reaction zone pressure is less than the mixing zone pressure so that expansion of the hydrate-forming gas in the mixture provides a degree of cooling by the Joule-Thompson effect and provides more intimate mixing between the water and the hydrate-forming gas. The result of the process is the formation of gas hydrates continuously and with a greatly reduced induction time. An apparatus for conduct of the method is further provided.

  17. Bioactivity And Bone Formation In Silicon-Substituted Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Ulvan Ozad

    2012-06-01

    Full Text Available Bioactivity and successful bone formation in silicon-substituted hydroxyapatite bone grafts were investigated by using scanning electron microscopy and electron dispersive x-ray spectroscopy. Areas of bone formation have been detected in scanning electron microscopy; and, arranged lamellar collagen has been observed. 20.8% average carbon content rise has been detected between bone graft and the produced bone; and, this has been confirmed to be a gradual increase throughout the interphase. Obvious bone formation and maturation were observed in the samples. Carbon content gradually increased from bone graft to the bone formed, confirming formation of new bone and dissociation of silicon-substituted bone graft.

  18. Heterotopic bone formation following total shoulder arthroplasty

    DEFF Research Database (Denmark)

    Kjaersgaard-Andersen, P.; Frich, Lars Henrik; Sjøbjerg, J.O.

    1989-01-01

    The incidence and location of heterotopic bone formation following total shoulder arthroplasty were evaluated in 58 Neer Mark-II total shoulder replacements. One year after surgery, 45% had developed some ectopic ossification. In six shoulders (10%) the ossifications roentgenographically bridged...... the glenohumeral and/or the glenoacromial space. There was no correlation between shoulder pain and the development of ossification. Shoulders with grade III heterotopic bone formation had a limited range of active elevation compared with shoulders without or with only a milder lesion. Men and patients...... with osteoarthritis of the shoulder joint were significantly disposed to the development of heterotopic bone. Heterotopic bone formation following total shoulder arthroplasty is frequent, but disabling heterotopic ossifications seem to be rare....

  19. Does simvastatin stimulate bone formation in vivo?

    Directory of Open Access Journals (Sweden)

    Chorev Michael

    2003-04-01

    Full Text Available Abstract Background Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS to the known anabolic effects of PTH in an established model of ovariectomized (OVX Swiss-Webster mice. Methods Mice were ovariectomized at 12 weeks of age (T0, remained untreated for 5 weeks to allow development of osteopenia (T5, followed by treatment for 8 weeks (T13. Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT. Liquid chromatography/mass spectrometry (LC/MS was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH in the mouse serum. Results Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day compared to the OVX-vehicle treated group (p in vivo study. Conclusions While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo.

  20. Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

    Science.gov (United States)

    Stein, Koen; Prondvai, Edina

    2014-02-01

    We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in

  1. Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Villasenor, Kelly S; Niu, Qing-Tian; Asuncion, Frank J; Xia, Xuechun; Grisanti, Mario; Wronski, Thomas J; Simonet, W Scott; Ke, Hua Zhu

    2018-01-01

    Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men. Copyright © 2018 Endocrine Society.

  2. A cellular automata model of bone formation.

    Science.gov (United States)

    Van Scoy, Gabrielle K; George, Estee L; Opoku Asantewaa, Flora; Kerns, Lucy; Saunders, Marnie M; Prieto-Langarica, Alicia

    2017-04-01

    Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus.

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    Donahue, Seth W; Vaughan, Michael R; Demers, Laurence M; Donahue, Henry J

    2003-12-01

    Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

  4. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    in the alterations of osteoblastogenesis and the resulting decline in bone formation with aging. Notably, the age-related osteoblast dysfunctions and defective bone formation are caused by a number of extrinsic clinical factors that inhibit anabolic signaling pathways in bone. Thus, targeting these pathways can......Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk...... of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify...

  5. Rapid prototyping technology and its application in bone tissue engineering.

    Science.gov (United States)

    Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

    Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

  6. Restoring the Architecture: A Rapid Clinical Perspective on Bone ...

    African Journals Online (AJOL)

    Restoring the Architecture: A Rapid Clinical Perspective on Bone-Mineral Density and Osteoporosis. 23. The page number in the footer is not for bibliographic referencing www.tandfonline.com/oemd. 23. • Vitamin D: Vital for calcium and phosphate absorption. Speculated to exert direct effects on bone, but the relevance of.

  7. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    Science.gov (United States)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  8. Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

    Science.gov (United States)

    Morgan, Jennifer L. L.; Skulan, Joseph L.; Gordon, Gwyneth W.; Romaniello, Stephen J.; Smith, Scott M.; Anbar, Ariel D.

    2012-06-01

    The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.

  9. Quantitative study of new bone formation in distraction osteogenesis of craniofacial bones by bone scintigraphy.

    Science.gov (United States)

    Rojvachiranonda, Nond; Tepmongkol, Supatporn; Mahatumarat, Charan

    2007-09-01

    Although distraction osteogenesis is widely accepted as a technique to augment the craniofacial skeleton, timing to start distraction after an osteotomy or to remove distractors is basically based on studies on long bones. Because bone scintigraphy is well known to be the gold standard for quantitative measurement of bone formation, we conducted this pilot study to evaluate its feasibility as a tool for assessing new bone formation by distraction osteogenesis. Five patients with midface hypoplasia and four with mandibular hypoplasia were studied. Each patient had five bone scans: before surgery, 3 and 30 days after stopping distraction, and 3 days before and 3 months after distractor removal. Radiotracer uptake values at distraction sites were measured at 1 and 3 hours. Each uptake value was compared with preoperative study as uptake ratio. A typical pattern of radiotracer uptake ratio was observed in all cases with successful distraction. Uptake rose to the maximum during the consolidation period and remained at or above the preoperative level until the study end point. In one patient who had mandibular distraction and nonunion of the right ramus, there was no uptake peak during early consolidation as seen in the successfully distracted body and in the other cases. Bone scintigraphy was found to be a useful investigation in craniofacial distraction. It showed the dynamic of new bone formation by demonstrating the osteoblastic activity, which is important objective information for determining distraction rate and consolidation duration in each case. It may also be a tool that can predict the outcome of distraction osteogenesis.

  10. Impact of bone graft harvesting techniques on bone formation and graft resorption

    DEFF Research Database (Denmark)

    Saulacic, Nikola; Bosshardt, Dieter D; Jensen, Simon S

    2015-01-01

    BACKGROUND: Harvesting techniques can affect cellular parameters of autogenous bone grafts in vitro. Whether these differences translate to in vivo bone formation, however, remains unknown. OBJECTIVE: The purpose of this study was to assess the impact of different harvesting techniques on bone fo......: Transplantation of autogenous bone particles harvested with four techniques in the present model resulted in moderate differences in terms of bone formation and graft resorption....

  11. Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair

    Science.gov (United States)

    Hinton, R.J.; Jing, Y.; Jing, J.; Feng, J.Q.

    2016-01-01

    The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID:27664203

  12. Impaired bone formation in Pdia3 deficient mice.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available 1α,25-Dihydroxyvitamin D3 [1α,25(OH2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3 mediates 1α,25(OH2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/- heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/- mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/- mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/- mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/- heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH2D3's actions in regulating skeletal development.

  13. Osteoclasts secrete non-bone derived signals that induce bone formation

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Neutzsky-Wulff, Anita V; Dziegiel, Morten Hanefeld

    2008-01-01

    Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, ...... secrete non-bone derived factors, which induce preosteoblasts to form bone-like nodules, potentially explaining the imbalanced coupling seen in osteopetrotic patients....

  14. Biomimetism, biomimetic matrices and the induction of bone formation.

    Science.gov (United States)

    Ripamonti, Ugo

    2009-09-01

    the induction of bone formation, the emergence of the skeleton, of the vertebrates and of Homo species * Different strategies for the induction of bone formation. Biological significance of redundancy and synergistic induction of bone formation. Biomimetism and biomimetic matrices self-assembling the induction of bone formation The concavity: the shape of life and the induction of bone formation. Influence of geometry on the expression of the osteogenic phenotype. Conclusion and therapeutic perspectives on porous biomimetic matrices with intrinsic osteoinductivity Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-beta (TGF-beta) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavities assembled within biomimetic constructs. The assembly of a series of repetitive concavities within the biomimetic constructs is endowed with the striking prerogative of differentiating osteoblast-like cells attached to the biomimetic matrices initiating the induction of bone formation as a secondary response. Importantly, the induction of bone formation is initiated without the exogenous application of the osteogenic soluble molecular signals of the TGF-beta superfamily. This manuscript reviews the available data on this fascinating phenomenon, i.e. biomimetic matrices that arouse and set into motion the mammalian natural ability to heal thus constructing biomimetic matrices that in their own right set into motion inductive regenerative phenomena initiating the cascade of bone differentiation by induction biomimetizing the remodelling cycle of the primate cortico-cancellous bone.

  15. A Rapid Clinical Perspective on Bone-Mineral Density and ...

    African Journals Online (AJOL)

    reduce intestinal calcium absorption, increase RANKL and. CSF-1 production,18 decrease IGF-1 production, and diminish the osteoblastic cell population.19. • Thyroid hormone: Important for cartilage formation, especially during childhood. Also bolsters bone resorption and collagenase production during adulthood.20.

  16. Investigating bone chip formation in craniotomy.

    Science.gov (United States)

    Huiyu, He; Chengyong, Wang; Yue, Zhang; Yanbin, Zheng; Linlin, Xu; Guoneng, Xie; Danna, Zhao; Bin, Chen; Haoan, Chen

    2017-10-01

    In a craniotomy, the milling cutter is one of the most important cutting tools. The operating performance, tool durability and cutting damage to patients are influenced by the tool's sharpness, intensity and structure, whereas the cutting characteristics rely on interactions between the tool and the skull. In this study, an orthogonal cutting experiment during a craniotomy of fresh pig skulls was performed to investigate chip formation on the side cutting and face cutting of the skull using a high-speed camera. The cutting forces with different combinations of cutting parameters, such as the rake angle, clearance angle, depth of cut and cutting speed, were measured. The skull bone microstructure and cutting damage were observed by scanning electron microscope. Cutting models for different cutting approaches and various depths of cut were constructed and analyzed. The study demonstrated that the effects of shearing, tension and extrusion occur during chip formation. Various chip types, such as unit chips, splintering chips and continuous chips, were generated. Continuous pieces of chips, which are advisable for easy removal from the field of operation, were formed at greater depths of cut and tool rake angles greater than 10°. Cutting damage could be relieved with a faster recovery with clearance angles greater than 20°.

  17. Biomimetism, biomimetic matrices and the induction of bone formation

    OpenAIRE

    Ripamonti, Ugo

    2008-01-01

    Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-? (TGF-?) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavit...

  18. Assessment of Mechanical Performance of Bone Architecture Using Rapid Prototyping Models

    Science.gov (United States)

    Saparin, Peter; Woesz, Alexander; Thomsen, Jasper S.; Fratzl, Peter

    2008-06-01

    The aim of this on-going research project is to assess the influence of bone microarchitecture on the mechanical performance of trabecular bone. A testing chain consist-ing of three steps was established: 1) micro computed tomography (μCT) imaging of human trabecular bone; 2) building of models of the bone from a light-sensitive polymer using Rapid Prototyping (RP); 3) mechanical testing of the models in a material testing machine. A direct resampling procedure was developed to convert μCT data into the format of the RP machine. Standardized parameters for production and testing of the plastic models were established by use of regular cellular structures. Next, normal, osteoporotic, and extreme osteoporotic vertebral trabecular bone architectures were re-produced by RP and compression tested. We found that normal architecture of vertebral trabecular bone exhibit behaviour characteristic of a cellular structure. In normal bone the fracture occurs at much higher strain values that in osteoporotic bone. After the fracture a normal trabecular architecture is able to carry much higher loads than an osteoporotic architecture. However, no statistically significant differences were found in maximal stress during uniaxial compression of the central part of normal, osteoporotic, and extreme osteoporotic vertebral trabecular bone. This supports the hypothesis that osteoporotic trabecular bone can compensate for a loss of trabeculae by thickening the remaining trabeculae in the loading direction (compensatory hypertrophy). The developed approach could be used for mechanical evaluation of structural data acquired non-invasively and assessment of changes in performance of bone architecture.

  19. Lutein, a carotenoid, suppresses osteoclastic bone resorption and stimulates bone formation in cultures.

    Science.gov (United States)

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

    2017-02-01

    Lutein, a member of the xanthophyll family of carotenoids, suppressed IL-1-induced osteoclast differentiation and bone resorption. The survival of mature osteoclasts was also suppressed by lutein in cultures. When lutein was added to the cultures of osteoblasts, lutein enhanced the formation of mineralized bone nodules by elevating BMP2 expression and inhibiting sclerostin expression. Lutein may be beneficial for bone health.

  20. No increased bone formation around alendronate or omeprazole loaded bioactive bone cements in a femoral defect.

    NARCIS (Netherlands)

    Bodde, E.W.H.; Kowalski, R.S.; Spauwen, P.H.M.; Jansen, Jarno

    2008-01-01

    Alendronate and omeprazole have been found to influence bone healing by interfering with osteoclastic activity, resulting in increased bone formation. The biological effect of these conventional drugs, incorporated into bioactive bone cement (G2B1), was investigated in a rabbit model. The 2

  1. Load regulates bone formation and Sclerostin expression through a TGFβ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Jacqueline Nguyen

    Full Text Available Bone continually adapts to meet changing physical and biological demands. Osteoblasts, osteoclasts, and osteocytes cooperate to integrate these physical and biochemical cues to maintain bone homeostasis. Although TGFβ acts on all three of these cell types to maintain bone homeostasis, the extent to which it participates in the adaptation of bone to mechanical load is unknown. Here, we investigated the role of the TGFβ pathway in load-induced bone formation and the regulation of Sclerostin, a mechanosensitive antagonist of bone anabolism. We found that mechanical load rapidly represses the net activity of the TGFβ pathway in osteocytes, resulting in reduced phosphorylation and activity of key downstream effectors, Smad2 and Smad3. Loss of TGFβ sensitivity compromises the anabolic response of bone to mechanical load, demonstrating that the mechanosensitive regulation of TGFβ signaling is essential for load-induced bone formation. Furthermore, sensitivity to TGFβ is required for the mechanosensitive regulation of Sclerostin, which is induced by TGFβ in a Smad3-dependent manner. Together, our results show that physical cues maintain bone homeostasis through the TGFβ pathway to regulate Sclerostin expression and the deposition of new bone.

  2. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed...

  3. Course and rate of post-fracture bone healing in correlation with bone-specific alkaline phosphatase and bone callus formation.

    Science.gov (United States)

    Muljacić, Ante; Poljak-Guberina, Renata; Zivković, Ognjen; Bilić, Vide; Guberina, Marko; Crvenković, Dalibor

    2013-12-01

    indicates successful fracture fixation, rapid bone healing and the formation of a minimal or insignificant callus. A major increase in the activity of the biochemical parameters ALP and S-bone ALP in the period of the first two weeks indicates inadequate fracture fixation, delayed bone healing and the formation of a visible and significant callus.

  4. Formation of blood clot on biomaterial implants influences bone healing.

    Science.gov (United States)

    Shiu, Hoi Ting; Goss, Ben; Lutton, Cameron; Crawford, Ross; Xiao, Yin

    2014-12-01

    The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

  5. Controlled delivery of zoledronate improved bone formation locally in vivo.

    Directory of Open Access Journals (Sweden)

    Wenlong Gou

    Full Text Available Bisphosphonates (BPs have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively than control and low-dose Zol (3 µg PLGA-Zol; p<0.05. Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation.

  6. Disassociation of bone resorption and formation by GLP-2

    DEFF Research Database (Denmark)

    Henriksen, Dennis B; Alexandersen, Peter; Hartmann, Bolette

    2007-01-01

    of collagen type I (s-CTX and u-CTX) and u-DPD, markers of bone resorption. In contrast, bone formation, as assessed by serum osteocalcin and procollagen type I N-terminal propeptide (PINP), appeared to be unaffected by treatment with exogenous GLP-2. These effects were further investigated in a 14-day study...

  7. Mushroom Extracts Decrease Bone Resorption and Improve Bone Formation.

    Science.gov (United States)

    Erjavec, Igor; Brkljacic, Jelena; Vukicevic, Slobodan; Jakopovic, Boris; Jakopovich, Ivan

    2016-01-01

    Mushroom extracts have shown promising effects in the treatment of cancer and various chronic diseases. Osteoporosis is considered one of the most widespread chronic diseases, for which currently available therapies show mixed results. In this research we investigated the in vitro effects of water extracts of the culinary-medicinal mushrooms Trametes versicolor, Grifola frondosa, Lentinus edodes, and Pleurotus ostreatus on a MC3T3-E1 mouse osteoblast-like cell line, primary rat osteoblasts, and primary rat osteoclasts. In an animal osteoporosis model, rats were ovariectomized and then fed 2 mushroom blends of G. frondosa and L. edodes for 42 days. Bone loss was monitored using densitometry (dual-energy X-ray absorptiometry) and micro computed tomography. In the concentration test, mushroom extracts showed no toxic effect on MC3T3-E1 cells; a dose of 24 µg/mL showed the most proliferative effect. Mushroom extracts of T. versicolor, G. frondosa, and L. edodes inhibited osteoclast activity, whereas the extract of L. edodes increased osteoblast mineralization and the production of osteocalcin, a specific osteoblastic marker. In animals, mushroom extracts did not prevent trabecular bone loss in the long bones. However, we show for the first time that the treatment with a combination of extracts from L. edodes and G. frondosa significantly reduced trabecular bone loss at the lumbar spine. Inhibitory properties of extracts from L. edodes on osteoclasts and the promotion of osteoblasts in vitro, together with the potential to decrease lumbar spine bone loss in an animal osteoporosis model, indicate that medicinal mushroom extracts can be considered as a preventive treatment and/or a supplement to pharmacotherapy to enhance its effectiveness and ameliorate its harmful side effects.

  8. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Warmington, Kelly S; Morony, Sean; Gong, Jianhua; Cao, Jin; Gao, Yongming; Shalhoub, Victoria; Tipton, Barbara; Haldankar, Raj; Chen, Qing; Winters, Aaron; Boone, Tom; Geng, Zhaopo; Niu, Qing-Tian; Ke, Hua Zhu; Kostenuik, Paul J; Simonet, W Scott; Lacey, David L; Paszty, Chris

    2009-04-01

    The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

  9. Biomimetic matrices self-initiating the induction of bone formation.

    Science.gov (United States)

    Ripamonti, Ugo; Roden, Laura C; Ferretti, Carlo; Klar, Roland M

    2011-09-01

    The new strategy of tissue engineering, and regenerative medicine at large, is to construct biomimetic matrices to mimic nature's hierarchical structural assemblages and mechanisms of simplicity and elegance that are conserved throughout genera and species. There is a direct spatial and temporal relationship of morphologic and molecular events that emphasize the biomimetism of the remodeling cycles of the osteonic corticocancellous bone versus the "geometric induction of bone formation," that is, the induction of bone by "smart" concavities assembled in biomimetic matrices of macroporous calcium phosphate-based constructs. The basic multicellular unit of the corticocancellous bone excavates a trench across the bone surface, leaving in its wake a hemiosteon rather than an osteon, that is, a trench with cross-sectional geometric cues of concavities after cyclic episodes of osteoclastogenesis, eventually leading to osteogenesis. The concavities per se are geometric regulators of growth-inducing angiogenesis and osteogenesis as in the remodeling processes of the corticocancellous bone. The concavities act as a powerful geometric attractant for myoblastic/myoendothelial and/or endothelial/pericytic stem cells, which differentiate into bone-forming cells. The lacunae, pits, and concavities cut by osteoclastogenesis within the biomimetic matrices are the driving morphogenetic cues that induce bone formation in a continuum of sequential phases of resorption/dissolution and formation. To induce the cascade of bone differentiation, the soluble osteogenic molecular signals of the transforming growth factor β supergene family must be reconstituted with an insoluble signal or substratum that triggers the bone differentiation cascade. By carving a series of repetitive concavities into solid and/or macroporous biomimetic matrices of highly crystalline hydroxyapatite or biphasic hydroxyapatite/β-tricalcium phosphate, we were able to embed smart biologic functions within

  10. Evaluation of heterotopic bone formation induced by squalane and bone morphogenetic protein composite.

    Science.gov (United States)

    Kawakami, T; Kawai, T; Takei, N; Kise, T; Eda, S; Urist, M R

    1997-04-01

    Bone morphogenetic protein is an important molecule whose bioactivity depends on the carrier. Squalane is used in the formulation of various kinds of cosmetics because it is easily emulsified and has the property of spreading well. Thus, squalane might be effective as a bone morphogenetic protein delivery system. As a test for this possibility, gelatin capsules containing squalane and bone morphogenetic protein (bovine derived partially purified) composite were implanted under the hind-quarter perimuscular membrane of ddY mice. Control capsules containing only bone morphogenetic protein were used for controls. The implants were radiographically and histologically examined at 1 to 4 weeks after the operation. According to the radiographic analysis, squalane and bone morphogenetic protein composite and bone morphogenetic protein only control specimens formed widespread heterotopic bone tissues. The amount of heterotopic bone formation in the composite experimental specimens was approximately 40% greater than that in the controls. Histologic examination of experimental and control specimens revealed varying amounts of perichondral ossification by 2 weeks. By 3 and 4 weeks, the bone deposits were colonized by hematopoietic bone marrow. Squalane was effective for the slow local release of bone morphogenetic protein. Furthermore, the squalane and bone morphogenetic protein composite was a reliable osteoinductive biomaterial.

  11. Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

    Science.gov (United States)

    2013-04-29

    Pediatrics, Pediatrics- Nutrition , Baylor College of Medicine, Houston, TX, USA 5Department of Pediatrics, Hematology-Oncology, Baylor College of...undergoing differentiation (Fig. 7A–F). DISCUSSION Heterotopic ossification is a disorder involving rapid bone formation within muscle, tendon , and

  12. Clay-Enriched Silk Biomaterials for Bone Formation

    Science.gov (United States)

    Mieszawska, Aneta J.; Llamas, Jabier Gallego; Vaiana, Christopher A.; Kadakia, Madhavi P.; Naik, Rajesh R.; Kaplan, David L.

    2011-01-01

    The formation of silk protein/clay composite biomaterials for bone tissue formation is described. Silk fibroin serves as an organic scaffolding material offering mechanical stability suitable for bone specific uses. Clay montmorillonite (Cloisite ® Na+) and sodium silicate are sources of osteoinductive silica-rich inorganic species, analogous to bioactive bioglass-like bone repair biomaterial systems. Different clay particle-silk composite biomaterial films were compared to silk films doped with sodium silicate as controls for support of human bone marrow derived mesenchymal stem cells (hMSCs) in osteogenic culture. The cells adhered and proliferated on the silk/clay composites over two weeks. Quantitative real-time RT-PCR analysis revealed increased transcript levels for alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col I) osteogenic markers in the cells cultured on the silk/clay films in comparison to the controls. Early evidence for bone formation based on collagen deposition at the cell-biomaterial interface was also found, with more collagen observed for the silk films with higher contents of clay particles. The data suggest that the silk/clay composite systems may be useful for further study toward bone regenerative needs. PMID:21549864

  13. Roles of Wnt signaling in bone formation and resorption

    Directory of Open Access Journals (Sweden)

    Yasuhiro Kobayashi

    2008-07-01

    Full Text Available Wnt proteins (Wnts are palmitoylated and glycosylated ligands that play a central role in the early development of organs and tissues. The discovery that loss-of-function mutations in low density lipoprotein receptor-related protein 5 (LRP5, a Wnt co-receptor, led to low bone mass in humans revealed the possible role of Wnt signaling in the regulation of bone remodeling. Many findings obtained from detailed analyses of mice having mutations of Wnt signaling molecules have confirmed that Wnt signaling has potential roles in bone remodeling in both physiological and pathological conditions. There are two pathways of Wnt signaling: β-catenin-dependent canonical and -independent non-canonical pathways. Wnts act on osteoblast precursor cells and promote their differentiation into mature osteoblasts through the β-catenin-dependent canonical pathway. In addition, Wnts suppress bone resorption by regulating the receptor activator of NF-κB ligand (RANKL/osteoprotegerin (OPG ratio through the same pathway in mature osteoblasts. In contrast, recent studies have shown that the activation of the β-catenin-independent non-canonical pathway enhances the RANKL-induced osteoclast formation in mouse macrophage cultures. These results indicate that Wnt-mediated signals are involved in several aspects of bone formation and bone resorption. This review will summarize the current knowledge of the roles of Wnt signaling in bone formation and resorption.

  14. Regulation of BMP-induced ectopic bone formation by Ahsg.

    Science.gov (United States)

    Rittenberg, B; Partridge, E; Baker, G; Clokie, C; Zohar, R; Dennis, J W; Tenenbaum, H C

    2005-05-01

    alpha2-HS-glycoprotein (Ahsg), also known as fetuin is a serum and bone resident glycoprotein, which binds to TGF-beta superfamily members including bone morphogenetic proteins (BMP) and inhibits dexamethasone-induced osteogenesis in bone marrow cultures in vitro. Here we demonstrate that Ahsg reduces cytokine binding to its cognate receptor in HOS osteocyte cells and suppresses intracellular signaling, while in vivo, we test the hypothesis that Ahsg-deficient mice are hyper-responsive to BMP-induced osteogenesis. Human native BMP was implanted into the hindquarter muscles of Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) mice and 4 weeks later, ossicle formation was analyzed by radiography, bone density scanning (DEXA) and histomorphometry. Alkaline phosphatase (AP) activity was measured in ossicles as a marker for bone cell differentiation, and was significantly higher in Ahsg(-/-) versus Ahsg(+/-) and/or Ahsg(+/+) mice. Ectopic ossicle size in the Ahsg(+/-) mouse was 4-fold greater than that in the wild type (Ahsg(+/+)), and intermediate to that shown in Ahsg(-/-) mouse. Bone mineral density (BMD) was lower in the Ahsg(-/+) and Ahsg(-/-) mice compared to Ahsg(+/+) littermates. The ratio of cortical to cancellous bone was found to be >2-fold higher in Ahsg(-/-) mouse in comparison to the Ahsg(+/+) mice with no significant change in the Ahsg(-/+) mouse. Finally, a significantly higher incidence of satellite ossification; small islands of immature bone, was shown in Ahsg(-/-) mice as compared to Ahsg(+/+) mice. Although Ahsg binds to TGF-beta/BMP and blocks receptor signalling, it may also sequester cytokines in matrix, thereby acting as a reservoir of osteoinductive activity when released. This may explain the non-linear relationship between ectopic bone formation characteristics and Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) genotypes, although the increase in satellite bone formation might also explain this phenomenon. Our results suggest that Ahsg may be useful for prevention of

  15. Addition of a Synthetically Fabricated Osteoinductive Biphasic Calcium Phosphate Bone Graft to BMP2 Improves New Bone Formation.

    Science.gov (United States)

    Zhang, Yufeng; Yang, Shuang; Zhou, Wei; Fu, Hang; Qian, Li; Miron, Richard J

    2016-12-01

    Bone morphogenetic protein-2 (BMP2) has been successfully utilized in dentistry to promote new bone formation because of its osteoinductive ability to recruit mesenchymal progenitor cells and induce their differentiation to bone-forming osteoblasts. Recently, novel biphasic calcium phosphate scaffolds have been developed with similar osteoinductive properties capable of forming ectopic bone formation. The aim of the present study was to assess whether the combination of BMP2 with this novel Biphasic Calcium Phosphate (BCP) scaffold may additionally promote new bone regeneration. Cylindrical bone defects measuring 2.5 mm were created bilaterally in the femurs of 18 Wistar rats. After 4 weeks, the following six groups were assessed for new bone formation by micro-computed tomography (CT) as well as histological assessment: 1) collagen scaffolds + 20 μg of BMP2; 2) collagen scaffolds + 50 μg of BMP2; 3) collagen scaffolds + 100 μg of BMP2; 4) BCP scaffolds + 20 μg of BMP2; 5) BCP scaffolds + 50 μg of BMP2; and 6) BCP scaffolds + 100 μg of BMP2. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining was utilized to assess osteoclast activity and osteoclast number. The release kinetics of BMP2 from both BCP and collagen scaffolds was investigated over a 14-day period. The results from present study demonstrate that BMP2 is able to promote new bone formation in a concentration dependant manner when loaded with either a collagen scaffolds or BCP scaffolds. Micro-CT analysis demonstrated significantly higher levels of new bone formation in groups containing BCP + BMP2 when compared with collagen scaffolds + BMP2. BMP2 had little effect on osteoclast activity; however, less TRAP staining and osteoclast number was observed in the defects receiving collagen scaffolds when compared with BCP scaffolds. The release of BMP2 over time was rapidly released after 1 day on BCP scaffolds whereas a gradually release over

  16. Coupling of Bone Resorption and Formation in Real Time

    DEFF Research Database (Denmark)

    Lassen, Nicolai Ernlund; Andersen, Thomas Levin; Pløen, Gro Grunnet

    2017-01-01

    measurements show that the latter contribute the most to overall resorption. Of note, the density of osteoprogenitors continuously grew along the "reversal/resorption" surface, reaching at least 39 cells/mm on initiation of bone formation. This value was independent of the length of the reversal......It is well known that bone remodeling starts with a resorption event and ends with bone formation. However, what happens in between and how resorption and formation are coupled remains mostly unknown. Remodeling is achieved by so-called basic multicellular units (BMUs), which are local teams...... of osteoclasts, osteoblasts, and reversal cells recently proven identical with osteoprogenitors. Their organization within a BMU cannot be appropriately analyzed in common histology. The originality of the present study is to capture the events ranging from initiation of resorption to onset of formation...

  17. Decrease of bone formation in adult women with fragility fractures.

    Science.gov (United States)

    Luisetto, G; Bottega, F; Nardi, A; Ziliotto, D

    1997-09-01

    To compare bone mineral density (BMD) and some markers of bone metabolism in women with fragility fractures and in normal age-matched subjects. A 100 women with at least one vertebral deformity > 25%, and 219 age-, BMI- and parity-matched healthy women, were recruited for the study. In all the patients fractures were symptomatic and occurred at least 1 year before densitometric measurement. Forearm bone mineral density (BMD) as well as biochemical assessment of some markers of bone turnover were measured in all the subjects. BMD was significantly lower in the fracture than in the control group (0.326 +/- 0.073 vs. 0.379 +/- 0.079; P < 0.001). Fractured women showed alkaline phosphatase (ALP) and osteocalcin (OC) serum levels significantly lower than controls, while no differences were found in fasting urinary calcium and hydroxyproline excretion. Women without fractures showed a significant correlation between ALP and both age and years since menopause (YSM). Such a correlation is lacking in the fracture group. Women with vertebral deformities likely due to a fracture had a forearm BMD and markers of bone formation lower than normal. Whether low bone density is due to a low peak of bone mass or to an increased postmenopausal bone loss sustained by an uncoupling between the two bone remodelling processes is still unclear.

  18. The Effect of Aloe, Gelfoam, Plaster on Bone Formation in applying to the bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eui Hwan [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Chosun University and Oral Biology Research Center, Kwangju (Korea, Republic of); Kim, Su Gwan [Dept. of Oral and Maxillofacial Surgery, College of Dentistry, Chosun University and Oral Biology Research Center, Kwangju (Korea, Republic of)

    1999-08-15

    This study was to evaluate the effects of Aloe, Gelfoam, and Plaster of Paris on bone healing. Four experimental defects were created for placement of the three materials in the right femur of dogs. One defect served as an empty control site. The evaluation was performed at 1-, 6-, and 12-weeks by light microscopy and NIH image program. Radiographic and Histologic examinations showed new bone formation in the presence of Aloe, Gelfoam, and Plaster of Paris and similar bone healing reactions. On the basis of these findings, it was concluded that Aloe, Gelfoam, and Plaster of Paris may be adequate agents for use in bone procurement.

  19. Biomimetic Functionalized Surfaces and the Induction of Bone Formation.

    Science.gov (United States)

    Ripamonti, Ugo

    2017-11-01

    Tissue engineering still needs to assign the molecular basis of pattern formation, tissue induction, and morphogenesis: What next to morphogens and stem cells? Macroporous biomimetic matrices per se, without the addition of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family, remarkably initiate the induction of bone formation. Carving geometries within different calcium phosphate-based macroporous bioreactors we show that geometric cues imprinted within the macroporous spaces initiate the spontaneous induction of bone. Concavities biomimetize the remodeling cycle of the primate osteonic bone and are endowed with functionalized smart geometric cues that per se initiate osteoblasts' differentiation with the expression and secretion of osteogenic molecular signals that induce bone as a secondary response. To study the role of calcium ions (Ca ++ ) and osteoclastogenesis, coral-derived calcium carbonate (CC)/hydroxyapatite (HA) bioreactors with limited conversion to HA (7% HA/CC) were preloaded with 500 μg of the L-type voltage gated calcium channel blocker verapamil hydrochloride. Bioreactors were also loaded with 240 μg of the bisphosphonate zoledronate, an osteoclast inhibitor, and implanted in heterotopic sites of the rectus abdominis muscle of Papio ursinus. Bisphosphonate-treated specimens were characterized by a delayed profoundly inhibited induction of tissue patterning with limited induction of bone. Macroporous constructs pretreated with verapamil hydrochloride yielded limited bone formation. Similarly, 125 or 150 μg human Noggin previously adsorbed onto the macroporous bioreactors resulted in minimal bone formation by induction, indirectly showing that the initiation of bone formation is through the bone morphogenetic protein (BMP) pathway. Downregulation of BMP-2 and osteogenic protein-1 (OP-1) with upregulation of Noggin correlated with limited bone induction. Angiogenesis, capillary sprouting

  20. [Application status of rapid prototyping technology in artificial bone based on reverse engineering].

    Science.gov (United States)

    Fang, Ao; Zheng, Min; Fan, Ding

    2015-02-01

    Artificial bone replacement has made an important contribution to safeguard human health and improve the quality of life. The application requirements of rapid prototyping technology based on reverse engineering in individualized artificial bone with individual differences are particularly urgent. This paper reviewed the current research and applications of rapid prototyping and reverse engineering in artificial bone. The research developments and the outlook of bone kinematics and dynamics simulation are also introduced.

  1. Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption.

    Science.gov (United States)

    Xiong, Lei; Jung, Ji-Ung; Wu, Haitao; Xia, Wen-Fang; Pan, Jin-Xiu; Shen, Chengyong; Mei, Lin; Xiong, Wen-Cheng

    2015-03-17

    Bone mass is maintained by balanced activity of osteoblasts and osteoclasts. Lrp4 (low-density lipoprotein receptor related protein 4) is a member of the LDL receptor family, whose mutations have been identified in patients with high-bone-mass disorders, such as sclerosteosis and van Buchem diseases. However, it remains unknown whether and how Lrp4 regulates bone-mass homeostasis in vivo. Here we provide evidence that Lrp4-null mutation or specific mutation in osteoblast-lineage cells increased cortical and trabecular bone mass, which was associated with elevated bone formation and impaired bone resorption. This phenotype was not observed in osteoclast-selective Lrp4 knockout mice. Mechanistic studies indicate that loss of Lrp4 function in osteoblast-lineage cells increased serum levels of sclerostin, a key factor for bone-mass homeostasis that interacts with Lrp4, but abolished the inhibition of Wnt/β-catenin signaling and osteoblastic differentiation by sclerostin. Concomitantly, sclerostin induction of RANKL (receptor activator of nuclear kappa B ligand) was impaired, leading to a lower ratio of RANKL over OPG (osteoprotegerin) (a key factor for osteoclastogenesis). Taken together, these results support the view for Lrp4 as a receptor of sclerostin to inhibit Wnt/β-catenin signaling and bone formation and identify Lrp4 as a critical player in bone-mass homeostasis.

  2. Rapid turnover of glycogen in memory formation.

    Science.gov (United States)

    Gibbs, Marie E; Hutchinson, Dana S

    2012-11-01

    The influence of noradrenaline acting at α(2)-AR and β(2)-ARs on the turnover of glycogen after learning has been investigated. The role of glycogen turnover in memory formation was examined using weakly-reinforced, single trial bead discrimination training in day-old domestic chickens. This study follows our previous work that focused on the need for glycogen breakdown (glycogenolysis) during learning. Inhibition of glycogenolysis by 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prevented the consolidation of strongly-reinforced learning and inhibited memory. The action of DAB could be prevented by stimulating glycogenolysis with the selective β(2)-AR agonist, zinterol. Stimulation of α(2)-ARs has been shown to lead to an increase in the turnover and synthesis of glycogen. In the present study, we examined the effect of inhibition of α(2)-AR stimulated glycogen turnover (measured as(14)C-glucose incorporation into glycogen) on the ability of zinterol to promote the consolidation of weakly reinforced memory. In astrocytes, the selective α(2)-AR agonist clonidine stimulated (14)C-glucose incorporation into glycogen in chick astrocytes and this was inhibited by the selective α(2)-AR antagonist, ARC239. The critical importance of the timing of ARC239 injection relative to training and intracerebral administration of zinterol was examined. It is concluded that our data provides evidence for a readily accessible labile pool of glycogen in brain astrocytes. If glycogen synthesis is inhibited, the can be depleted within 10 min, thus preventing zinterol from promoting consolidation.

  3. Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Zihui Li

    Full Text Available Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (remodeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (remodeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

  4. Subchondral Bone Plate Changes More Rapidly than Trabecular Bone in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zaitunnatakhin Zamli

    2016-09-01

    Full Text Available Osteoarthritis (OA is the most common joint disorder, characterised by focal loss of cartilage and increased subchondral bone remodelling at early OA stages of the disease. We have investigated the temporal and the spatial relationship between bone remodelling in subchondral bone plate (Sbp and trabecular bone (Tb in Dunkin Hartley (DH, develop OA early and the Bristol Strain 2 (BS2, control which develop OA late guinea pigs. Right tibias were dissected from six male animals of each strain, at 10, 16, 24 and 30 weeks of age. Micro-computed tomography was used to quantify the growth plate thickness (GpTh, subchondral bone plate thickness (SbpTh and trabecular bone thickness (TbTh, and bone mineral density (BMD in both Sbp and Tb. The rate of change was calculated for 10–16 weeks, 16–24 weeks and 24–30 weeks. The rate of changes in Sbp and Tb thickness at the earliest time interval (10–16 weeks were significantly greater in DH guinea pigs than in the growth-matched control strain (BS2. The magnitude of these differences was greater in the medial side than the lateral side (DH: 22.7 and 14.75 µm/week, BS2: 5.63 and 6.67 µm/week, respectively. Similarly, changes in the BMD at the earliest time interval was greater in the DH strain than the BS2, again more pronounced in the disease prone medial compartment (DH: 0.0698 and 0.0372 g/cm3/week, BS2: 0.00457 and 0.00772 g/cm3/week, respectively. These changes observed preceded microscopic and cellular signs of disease as previously reported. The rapid early changes in SbpTh, TbTh, Sbp BMD and Tb BMD in the disease prone DH guinea pigs compared with the BS2 control strain suggest a link to early OA pathology. This is corroborated by the greater relative changes in subchondral bone in the medial compared with the lateral compartment.

  5. Regulation of bone formation and resorption by Beta Adrenergic system

    Directory of Open Access Journals (Sweden)

    Fateme Mohammadali

    2016-04-01

    Full Text Available Background Following initial studies reporting the presence of βeta adrenergic receptors on bone cells, several studies have investigated the role of the Beta adrenergic system in the formation and resorption of bone. The goal of this report was to review the data supporting the role of the  beta adrenergic system and osteo-neuromediators in the regulation of bone homeostasis. Materials and Methods: In this review, more than 100 published articles were reviewed for the evidence of the adrenergic effect on bone remodeling and focused on the latest advances in this area. Results: Based on a variety of pharmacologic, genetic and clinical studies focused on b-adrenergic receptor (bAR signaling in bone cells, The adrenergic activity of the sympathetic nervous system has been shown to be a negative regulator of bone mass; adrenergic signaling inhibits osteoblast proliferation and promotes osteoclastogenesis . Conclusion: Altogether, these observations and linked findings are of great significance since they improve our understanding of bone physiology., and uncovered new potential therapeutic strategies for the design of bone anabolic drugs. Certainly, knowledge about downstream factors of beta-adrenergic system can be helpful in making decisions about appropriate therapeutic interventions.

  6. Effects of phenylbutazone on bone activity and formation in horses.

    Science.gov (United States)

    Rohde, C; Anderson, D E; Bertone, A L; Weisbrode, S E

    2000-05-01

    To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses. 12 healthy 1- to 2-year-old horses. Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ. MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ. PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses.

  7. [Primary cancellous bone formation around micro-chambered beads].

    Science.gov (United States)

    Draenert, M E; Draenert, Y; Draenert, K; Pohlemann, T; Erler, M

    2014-01-01

    The question has been raised whether benign bone defects in patients can be treated with bone forming osteoconductive ceramics achieving primarily a cancellous bone scaffold, which is under load from the beginning. Ten reconstructions were performed in 9patients (6women and 3male), with a mean age of 49 (25-65)years, suffering a high variety of epi- and metaphyseal defects, four tibial fractures, two calcaneal fractures, one pathological phalangeal fracture, one chondroma of the distal femur and two open-wedge osteotomies were filled with micro-chambered ceramic beads of 4 and 6mm in diameter. The mean follow up was 22 (7- 8)months. X-rays and CT-scans formed the basis for the evaluation of the reconstruction of the cancellous bone scaffolds. All cancellous structures were rebuilt, if completely filled with bone-forming elements. If the filling was incomplete, no physiological cancellous bone scaffold resulted. The β-TCP micro-chambered beads were completely reabsorbed or sandwich-like incorporated at the time of evaluation. The HA micro-chambered beads revealed a contrast enhancement and were integrated in the osseous construction of the bone scaffold. Primary cancellous bone formation can be achieved with osteoconductive ceramic micro-chambered beads and can be combined with any osteosynthesis for stable fixation. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  8. Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion

    Directory of Open Access Journals (Sweden)

    Xiaoxia Che

    2016-01-01

    Full Text Available Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components.

  9. Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion

    Science.gov (United States)

    Guo, Jie; Wang, Lue; Miao, Cong; Ge, Lihua; Tian, Zhenchuan; Wang, Jianhong

    2016-01-01

    Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components. PMID:27478838

  10. Non-linear pattern formation in bone growth and architecture.

    Science.gov (United States)

    Salmon, Phil

    2014-01-01

    The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here - chaotic non-linear pattern formation (NPF) - which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of "group intelligence" exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called "particle swarm optimization" (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating "socially" in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or "feedback" between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent

  11. Vibration acceleration promotes bone formation in rodent models.

    Science.gov (United States)

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  12. Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture

    Directory of Open Access Journals (Sweden)

    Kazancioglu HO

    2015-12-01

    Full Text Available Hakki Oguz Kazancioglu,1 Sertac Aksakalli,2 Seref Ezirganli,1 Muhammet Birlik,2 Mukaddes Esrefoglu,3 Ahmet Hüseyin Acar1 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, Faculty of Dentistry, 3Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new application has been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE on new bone formation in rat midpalatal suture after RME.Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess of new bone formation.Results: New bone formation was significantly greater in CAPE group than the control group (P<0.05. CAPE enhances new bone formation in midpalatal suture after RME.Conclusion: These results show that CAPE may decrease the time needed for retention. Keywords: rapid maxillary expansion, bone formation, caffeic acid phenethyl ester, midpalatal suture, histopathology

  13. Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model

    Science.gov (United States)

    2014-01-01

    Background Porphyromonas gingivalis has been shown to invade osteoblasts and inhibit their differentiation and mineralization in vitro. However, it is unclear if P. gingivalis can invade osteoblasts in vivo and how this would affect alveolar osteoblast/osteoclast dynamics. This study aims to answer these questions using a periodontitis mouse model under repetitive P. gingivalis inoculations. Methods For 3-month-old BALB/cByJ female mice, 109 CFU of P. gingivalis were inoculated onto the gingival margin of maxillary molars 4 times at 2-day intervals. After 2 weeks, another 4 inoculations at 2-day intervals were applied. Calcein was injected 7 and 2 days before sacrificing animals to label the newly formed bone. Four weeks after final inoculation, mice were sacrificed and maxilla collected. Immunohistochemistry, micro-CT, and bone histomorphometry were performed on the specimens. Sham infection with only vehicle was the control. Results P. gingivalis was found to invade gingival epithelia, periodontal ligament fibroblasts, and alveolar osteoblasts. Micro-CT showed alveolar bone resorption and significant reduction of bone mineral density and content in the infected mice compared to the controls. Bone histomorphometry showed a decrease in osteoblasts, an increase in osteoclasts and bone resorption, and a surprisingly increased osteoblastic bone formation in the infected mice compared to the controls. Conclusions P. gingivalis invades alveolar osteoblasts in the periodontitis mouse model and cause alveolar bone loss. Although P. gingivalis appears to suppress osteoblast pool and enhance osteoclastic bone resorption, the bone formation capacity is temporarily elevated in the infected mice, possibly via some anti-microbial compensational mechanisms. PMID:25027664

  14. Bone formation by autogenous grafting of cultured bone/porous ceramic constructs in a dog

    Energy Technology Data Exchange (ETDEWEB)

    Iida, J.; Ueda, Y.; Ohgushi, H.; Takakura, Y. [Nara Medical Univ., Kashihara (Japan). Dept. of Orthopedic Surgery; Yoshikawa, T. [Nara Medical Univ., Kashihara (Japan). Dept. of Orthopedic Surgery; Nara Medical Univ., Kashihara (Japan). Dept. of Phathology; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara (Japan). Dept. of Phathology

    2001-07-01

    Five ml of bone marrow was collected from the humerus of a 6 month old female dog by needle aspiration. The marrow was cultured in T-75 flask and expand the marrow mesenchymal cells. After 1 week in primary culture, cells were released by trypsin treatment, concentrated and loaded onto porous hydroxyapatite (HA) blocks. The marrow/HA constructs were subcultured in the presence of dexamethasone and beta-glycerophosphate (osteogenic medium). After 2 weeks of subculture, the autogenous cultured bone/HA constructs were subcutaneously implanted into the back of the dog. Histological findings of the constructs at 3 weeks after implantation revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the HA. High alkaline phosphatase activity could be detected in the construct. These results indicate that autogenous cultured bone/HA constructs can produce extensive bone formation after implantation in a large animal(dog). Therefore, based upon the fact that human marrow-derived culture bone/HA construct possesses osteogenic potential when it is grafted into nude mice, it can be expected that autogenous human cultured bone/ceramic grafts may be useful to reconstruct bone in the clinical setting. (orig.)

  15. Normal tempo of bone formation in Turner syndrome despite signs of accelerated bone resorption

    DEFF Research Database (Denmark)

    Cleemann, Line Hartvig; Holm, Kirsten Bagge; Kobbernagel, Hanne

    2011-01-01

    Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n......' TS, compared to controls. vBMD(hip) was lower in 'ongoing GH' TS, but similar in 'previous GH'. z scores for aBMD were uniformly reduced in 'ongoing TS', but near-normalized in 'previous GH' TS. Bone formation and resorption markers were increased in 'ongoing GH' TS, while 'previous GH' TS had...... elevated bone resorption markers. Conclusion: BMD increased in parallel with age in TS patients receiving optimal estradiol replacement therapy and GH according to consensus guidelines, and in controls. Young TS undergoing pubertal induction and still receiving GH have lower z score BMD than older TS...

  16. Osteoclast formation from peripheral blood of patients with bone-lytic diseases

    NARCIS (Netherlands)

    de Vries, T.J.; Everts, V.

    2009-01-01

    Recent literature indicates that osteoclast formation in vitro from peripheral blood of patients with diseases associated with bone loss such as rheumatoid arthritis, osteoporosis, periodontitis and bone metastatic cancer may occur spontaneously being independent of addition of osteoclast formation

  17. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L

    2014-01-01

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the ost......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...... osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is the physical site where coupling of bone resorption to bone formation occurs....

  18. Early effects of prostaglandin E2 on bone formation and resorption in different bone sites of rats.

    Science.gov (United States)

    Lin, C H; Jee, W S; Ma, Y F; Setterberg, R B

    1995-10-01

    The aim of this study was to determine early effects of prostaglandin E2 (PGE2) on bone mass, formation and resorption in a growing cancellous bone site (the proximal tibial metaphysis, PTM), non-growing cancellous bone site (the distal tibial metaphysis, DTM), and cortical bone site (the tibial shaft, TX) with histomorphometric analysis. Six mg PGE2/kg/d was given s.c. to 6-month-old Sprague-Dawley female rats for 5, 10 or 16 days. Double fluorescent labels were given to 0, 10- and 16-day PGE2 treatment and 16-day control groups. Significant increase in bone mass was found after 16 days treatment in cancellous bone sites but not in the cortical bone site. Stimulated bone formation, indicated by the increase in osteoid perimeter, was observed as early as 5 days post-treatment in all 3 bone sites. Bone formation indices were increased after 10 days of treatment, however, there was no difference in selected bone formation indices between 10 and 16 days PGE2 treatments at all 3 bone sites. Significant increase in eroded surface and eroded surface covered with osteoid was observed in cancellous bone sites after 5 days, but decreased after 10 days of treatment. Although the eroded surface was not elevated in TX at the 5th day, the eroded surface covered with osteoid was increased on endocortical surface which indicated that PGE2 stimulated bone resorption on this surface prior to day 5. We concluded that PGE2 stimulated the bone formation and resorption as early as 5 days post-treatment. The levels of stimulated bone formation was TX > DTM > PTM.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Seasonal variations in indices of bone formation precede appropriate bone mineral changes in normal men

    Energy Technology Data Exchange (ETDEWEB)

    Hyldstrup, L.; McNair, P.; Jensen, G.F.; Transbol, I.

    1986-01-01

    In 10 normal males aged 23-50 years measurements of serum alkaline phosphatase (s-AP) and the 24-h whole body retention of 99mTc-diphosphonate (WBR), as indices of bone formation, and the fasting urinary hydroxyproline:creatinine ratio (OHPr:Cr), as an index of bone resorption, were performed monthly from January 1983 to May 1984. Bone mineral content of the distal forearm (BMC) was measured in the middle of each quarter. From January to May BMC exhibited a reproducible, significant average increase of 2.5%, returning to baseline level between May and August. During the first quarter of both 1983 and 1984 a significant increase in s-AP and WBR was seen. Subsequently, during the second quarter of 1983, these variables fell below the mean of the year. Confirming their interrelationship, the deviations of s-AP and WBR were positively correlated throughout the study period (r = 0.51, P less than 0.05). Since the urinary OHPr:Cr ratio remained constant, the reported seasonal changes in bone mass of normal, adult males appear to result from primary changes in bone formation.

  20. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

    Science.gov (United States)

    Tenzer, Stefan; Docter, Dominic; Kuharev, Jörg; Musyanovych, Anna; Fetz, Verena; Hecht, Rouven; Schlenk, Florian; Fischer, Dagmar; Kiouptsi, Klytaimnistra; Reinhardt, Christoph; Landfester, Katharina; Schild, Hansjörg; Maskos, Michael; Knauer, Shirley K.; Stauber, Roland H.

    2013-10-01

    In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.

  1. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

    NARCIS (Netherlands)

    Song, G.; Habibovic, Pamela; Bao, Chongyun; Hu, J.; van Blitterswijk, Clemens; Yuan, Huipin; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched

  2. Metaphyseal bone formation induced by a new injectable β-TCP-based bone substitute: a controlled study in rabbits.

    Science.gov (United States)

    Krause, Matthias; Oheim, Ralf; Catala-Lehnen, Philip; Pestka, Jan M; Hoffmann, Christiane; Huebner, Wolf; Peters, Fabian; Barvencik, Florian; Amling, Michael

    2014-02-01

    Adequate filling of bone defects still poses a challenge in every day clinical work. As many bone defects are irregularly shaped the need for appropriate scaffolds reaching the complete defect surface are great. The purpose of this pre-clinical pilot study was to investigate the handling, biocompatibility, biodegradation and osteoconductivity of a new pasty bone substitute (pure phase β-TCP, hyaluronic acid, methylcellulose) in bone tissue. In an unilateral tibial defect model the peri-implant and bone tissue response to the new pasty bone substitute was tested in New Zealand white rabbits for up to 24 weeks compared to empty controls. Analysis included HR-pQCT scans, histomorphometric evaluation and quantification of vascularization of un-decalcified histological slices. After 1 week the experimental group presented significantly higher new bone volume fraction (p = 0.021) primarily consisting of immature bone matrix and higher vessel density compared to controls (p = 0.013). After 4 weeks bone formation was not significantly different to controls but was distributed more evenly throughout the defect. Bone matrix was now mineralized and trabeculae were thicker than in controls (p = 0.002) indicating faster intramedullary bone maturation. Controls presented extensive periosteal bone formation, major fibrous tissue influx and high vascularization. After 12 and 24 weeks there was no new bone detectable. There were no severe signs of inflammation at all time points. The substitute showed an early induction of bone formation. It promoted accelerated intramedullary bone repair and maturation and prevented periosteal bone formation indicating its potential use for reconstructive surgery of bone defects.

  3. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

    2004-01-01

    formation. This study indicates that chloride channel inhibitors are highly promising for treatment of osteoporosis. INTRODUCTION: The chloride channel inhibitor, NS3736, blocked osteoclastic acidification and resorption in vitro with an IC50 value of 30 microM. When tested in the rat ovariectomy model...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride......: In conclusion, we show for the first time that chloride channel inhibitors can be used for prevention of ovariectomy-induced bone loss without impeding bone formation. We speculate that the coupling of bone resorption to bone formation is linked to the acidification of the resorption lacunae, thereby enabling...

  4. Rapid prototyped porous nickel–titanium scaffolds as bone substitutes

    Directory of Open Access Journals (Sweden)

    Waldemar Hoffmann

    2014-06-01

    Full Text Available While calcium phosphate–based ceramics are currently the most widely used materials in bone repair, they generally lack tensile strength for initial load bearing. Bulk titanium is the gold standard of metallic implant materials, but does not match the mechanical properties of the surrounding bone, potentially leading to problems of fixation and bone resorption. As an alternative, nickel–titanium alloys possess a unique combination of mechanical properties including a relatively low elastic modulus, pseudoelasticity, and high damping capacity, matching the properties of bone better than any other metallic material. With the ultimate goal of fabricating porous implants for spinal, orthopedic and dental applications, nickel–titanium substrates were fabricated by means of selective laser melting. The response of human mesenchymal stromal cells to the nickel–titanium substrates was compared to mesenchymal stromal cells cultured on clinically used titanium. Selective laser melted titanium as well as surface-treated nickel–titanium and titanium served as controls. Mesenchymal stromal cells had similar proliferation rates when cultured on selective laser melted nickel–titanium, clinically used titanium, or controls. Osteogenic differentiation was similar for mesenchymal stromal cells cultured on the selected materials, as indicated by similar gene expression levels of bone sialoprotein and osteocalcin. Mesenchymal stromal cells seeded and cultured on porous three-dimensional selective laser melted nickel–titanium scaffolds homogeneously colonized the scaffold, and following osteogenic induction, filled the scaffold’s pore volume with extracellular matrix. The combination of bone-related mechanical properties of selective laser melted nickel–titanium with its cytocompatibility and support of osteogenic differentiation of mesenchymal stromal cells highlights its potential as a superior bone substitute as compared to clinically used

  5. Rapid cortical bone loss in patients with chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Stein, Emily M; Dworakowski, Elzbieta; Nishiyama, Kyle K; Komandah-Kosseh, Mafo; Zhang, Chiyuan A; McMahon, Donald J; Liu, Xiaowei S; Boutroy, Stephanie; Cremers, Serge; Shane, Elizabeth

    2013-08-01

    Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. Copyright © 2013 American Society for Bone and Mineral Research.

  6. Biologic properties of nano-hydroxyapatite: An in vivo study of calvarial defects, ectopic bone formation and bone implantation.

    Science.gov (United States)

    Pang, Kang-Mi; Lee, Jeong-Keun; Seo, Young-Kwon; Kim, Soung-Min; Kim, Myung-Jin; Lee, Jong-Ho

    2015-01-01

    This study investigated the biologic properties of nano-hydroxyapatite (nHAp) using the rat calvarial defect, ectopic bone formation, and rabbit tibia implant installation models. Animals were divided into two groups: those implanted with nHAp, and negative controls (Collagen). Eight weeks after creating an 8 mm calvarial defect, bone regeneration was evaluated radiographically and histologically. To investigate ectopic bone formation, materials were injected into the right thigh muscle and were evaluated after 8 weeks. nHAp coated implant and conventional titanium implant were placed bilaterally in rabbit tibias. After 4 weeks, bone-implant contact (BIC), new bone area inside the thread, and removal torque were measured. In the calvarial defect model, radiographic and histologic analysis showed more bone formation in the nHAp Group; particularly, histologically assessed bone area (p=0.034) and microcomputed tomography assessed bone mineral density (p=0.034). In the ectopic bone formation model, calcification and expression of osteogenic biomarkers were seen in the nHAp-injected samples but in none of the controls. nHAp coated implant resulted in increased BIC, new bone area, and increased removal torque, with statistical significance for BIC (p=0.034). This study suggests that nHAp has potential as a coating material for dental implant surfaces and as a bone graft material.

  7. Rapid formation of a sea ice barrier east of Svalbard

    Science.gov (United States)

    Nghiem, S. V.; van Woert, M. L.; Neumann, G.

    2005-11-01

    Daily SeaWinds scatterometer images acquired by the QuikSCAT satellite show an elongated sea ice feature that formed very rapidly (˜1-2 days) in November 2001 east of Svalbard over the Barents Sea. This sea ice structure, called "the Svalbard sea ice barrier," spanning approximately 10° in longitude and 2° in latitude, restricts the sea route and poses a significant navigation hazard. The secret of its formation appears to lie in the bottom of the sea: A comparison between bathymetry from the International Bathymetric Chart of the Arctic Ocean data and the pattern of sea ice formation from scatterometer data reveals that the sea ice barrier conforms well with and stretches above a deep elongated channel connecting the Franz Josef-Victoria Trough to the Hinlopen Basin between Svalbard and Franz Josef Land. Historic hydrographic data from this area indicate that this sea channel contains cold Arctic water less than 50 m below the surface. Strong and persistent cold northerly winds force strong heat loss from this shallow surface layer, leading to the rapid formation of the sea ice barrier. Heat transfer rates estimated from European Centre for Medium-Range Weather Forecasts temperature and wind data over this region suggest that the surface water along the deep channel can be rapidly cooled to the freezing point. Scatterometer results in 1999-2003 show that sea ice forms in this area between October and December. Understanding the ice formation mechanisms helps to select appropriate locations for deployment of buoys measuring wind and air-sea temperature profile and to facilitate ice monitoring, modeling, and forecasting.

  8. Direct bone formation during distraction osteogenesis does not require TNF alpha receptors and elevated serum TNF alpha fails to inhibit bone formation in TNFR1 deficient mice

    Science.gov (United States)

    Distraction osteogenesis (DO) is a process which induces direct new bone formation as a result of mechanical distraction. Tumor necrosis factor-alpha (TNF) is a cytokine that can modulate osteoblastogenesis. The direct effects of TNF on direct bone formation in rodents are hypothetically mediated th...

  9. Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles

    NARCIS (Netherlands)

    Visser, Jetze; Gawlitta, Debby; Benders, Kim E. M.; Toma, Selynda M. H.; Pouran, Behdad; van Weeren, P. Rene; Dhert, Wouter J. A.; Malda, J

    The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation,

  10. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study.

    Science.gov (United States)

    Cohen, Adi; Dempster, David W; Recker, Robert R; Lappe, Joan M; Zhou, Hua; Zwahlen, Alexander; Müller, Ralph; Zhao, Binsheng; Guo, Xiaotao; Lang, Thomas; Saeed, Isra; Liu, X Sherry; Guo, X Edward; Cremers, Serge; Rosen, Clifford J; Stein, Emily M; Nickolas, Thomas L; McMahon, Donald J; Young, Polly; Shane, Elizabeth

    2013-06-01

    The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P fat by computed tomography (r = 0.79, P fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm(2)/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = -0.50; P bone formation rate (r = -0.50; P relationship between trunk fat and bone volume remained significant after controlling for age and BMI. At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.

  11. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2010-02-01

    2001 Mar;22(5):439-444. 20. Sawhney AS, Pathak CP, Hubbell JA. Modification of islet of langerhans surfaces with immunoprotective poly(ethylene...vertebrae. Biomechanical Testing Prior to sectioning, formaldehyde fixed spines were encased in alginate in order to obtain flexion and extension...radiographs. Spines were suspended in an in-house mold. Alginate powder was combined in an equal volume to water (30 ml of each) and mixed until smooth

  12. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2009-02-01

    delivery of either the Ad5BMP2 transduced MRC5 cells or those encapsulated in hydrogel. As can be seen in figure 6, we still observe some signal...arrow: cell inoculation site White arrow: scar region Figure 4: Live animal optical imaging of nude mice which received 5 x 106 MRC5 cells transduced...Animal #1 Animal #2 Animal #1 Animal #2 031707 Figure 5: Live animal optical imaging of nude mice which received 5 x 106 MRC5 cells transduced with

  13. Bony defect repair in rabbit using hybrid rapid prototyping polylactic co glycolic acid/β tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Long Pang

    2013-01-01

    Full Text Available Background: In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP scaffolds comprising polylactic-co-glycolic acid (PLGA, β-tricalciumphosphate (β-TCP, collagen I and apatite (PLGA/β-TCP-collagen I/apatite on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs. Materials and Methods: BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation. Results: Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/β-TCP during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time. Conclusion: Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/β-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering.

  14. Bony defect repair in rabbit using hybrid rapid prototyping polylactic-co-glycolic acid/β-tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells

    Science.gov (United States)

    Pang, Long; Hao, Wei; Jiang, Ming; Huang, Jianguo; Yan, Yongnian; Hu, Yunyu

    2013-01-01

    Background: In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP) scaffolds comprising polylactic-co-glycolic acid (PLGA), β-tricalciumphosphate (β-TCP), collagen I and apatite (PLGA/β-TCP-collagen I/apatite) on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs). Materials and Methods: BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation. Results: Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/β-TCP) during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time. Conclusion: Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/β-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering. PMID:23960284

  15. Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

    Science.gov (United States)

    Li, Feng; Wang, Xujun; Niyibizi, Christopher

    2010-01-01

    Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

  16. The role of adaptive bone formation in the etiology of stress fracture.

    Science.gov (United States)

    Hughes, Julie M; Popp, Kristin L; Yanovich, Ran; Bouxsein, Mary L; Matheny, Ronald W

    2017-05-01

    Stress fractures are common injuries with load-bearing activities. Stress fractures have been reported in the scientific literature for over a century; however, the etiology continues to be investigated with important distinctions made between the contributions of the tissue-level processes of bone remodeling and modeling. In response to novel repetitive loading, increased bone remodeling may serve to replace fatigue-damaged bone while at the same time creating temporary porosity. Much attention has been given to the role of remodeling in the etiology of stress fracture; however, the role of bone modeling has received less attention. Modest increases in modeling, via bone formation on the periosteal surface of long bones in response to mechanical loading, greatly increases the fatigue resistance of bone. Thus, enhancing this adaptive bone formation is a promising target for stress fracture prevention, and a focus on adaptive bone formation may reveal novel risk factors for stress fracture.

  17. Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping.

    Science.gov (United States)

    Fradique, R; Correia, T R; Miguel, S P; de Sá, K D; Figueira, D R; Mendonça, A G; Correia, I J

    2016-04-01

    The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.

  18. 18F-fluoride Positron Emission Tomography Measurements of Regional Bone Formation in Hemodialysis Patients with Suspected Adynamic Bone Disease

    OpenAIRE

    Frost, Michelle L.; Compston, Juliet E.; Goldsmith, David; Moore, Amelia; Blake, Glen M; Siddique, Musib; Skingle, Linda; Fogelman, Ignac

    2013-01-01

    18F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan,...

  19. Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

    Science.gov (United States)

    Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

    2014-01-01

    Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

  20. Rapid and independent memory formation in the parietal cortex.

    Science.gov (United States)

    Brodt, Svenja; Pöhlchen, Dorothee; Flanagin, Virginia L; Glasauer, Stefan; Gais, Steffen; Schönauer, Monika

    2016-11-15

    Previous evidence indicates that the brain stores memory in two complementary systems, allowing both rapid plasticity and stable representations at different sites. For memory to be established in a long-lasting neocortical store, many learning repetitions are considered necessary after initial encoding into hippocampal circuits. To elucidate the dynamics of hippocampal and neocortical contributions to the early phases of memory formation, we closely followed changes in human functional brain activity while volunteers navigated through two different, initially unknown virtual environments. In one condition, they were able to encode new information continuously about the spatial layout of the maze. In the control condition, no information could be learned because the layout changed constantly. Our results show that the posterior parietal cortex (PPC) encodes memories for spatial locations rapidly, beginning already with the first visit to a location and steadily increasing activity with each additional encounter. Hippocampal activity and connectivity between the PPC and hippocampus, on the other hand, are strongest during initial encoding, and both decline with additional encounters. Importantly, stronger PPC activity related to higher memory-based performance. Compared with the nonlearnable control condition, PPC activity in the learned environment remained elevated after a 24-h interval, indicating a stable change. Our findings reflect the rapid creation of a memory representation in the PPC, which belongs to a recently proposed parietal memory network. The emerging parietal representation is specific for individual episodes of experience, predicts behavior, and remains stable over offline periods, and must therefore hold a mnemonic function.

  1. Greater Bone Formation Induction Occurred in Aged than Young Cancellous Bone Sites

    Science.gov (United States)

    Ke, H. Z.; Jee, W. S. S.; Ito, H.; Setterberg, R. B.; Li, M.; Lin, B. Y.; Liang, X. G.; Ma, Y. F.

    1993-01-01

    We have determined the differences in the effects of continual prostaglandin E(sub 2) (PGE(sub 2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE(sub 2)/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE(sub 2)/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE(sub 2) treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE(sub 2) treatment than young growing metaphysis.

  2. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice.

    Science.gov (United States)

    Hamrick, Mark W; Della-Fera, Mary Anne; Choi, Yang-Ho; Pennington, Catherine; Hartzell, Diane; Baile, Clifton A

    2005-06-01

    Normal mice and leptin-deficient ob/ob mice were treated with leptin to study effects on osteogenesis and adipogenesis in bone marrow. Leptin treatment significantly decreased bone marrow adipocyte size and number in ob/ob mice while increasing bone formation, BMC, and BMD. The results suggest that, in leptin-sensitive animals, the reduction in marrow adipocytes has positive effects on bone formation. Adipocytes, osteoblasts, and osteoclasts have leptin receptors, and leptin can also affect bone metabolism indirectly through its receptors in the hypothalamus. We examined the effects of leptin treatment on bone formation, BMD, and marrow adipocyte population in normal mice and leptin-deficient ob/ob mice. At the age of 15 weeks, mice were implanted with Alzet osmotic pumps for subcutaneous delivery of treatment solutions (saline, 2.5 microg leptin/day, or 10 microg leptin/day) for 14 days at a delivery rate of 0.25 microl/h. Bone formation was assessed using fluorochrome labels, cell populations were quantified using histomorphometry, and bone densitometry was measured using DXA. We also used a Luminex Beadlyte assay system to quantify cell survival markers in bone marrow samples. Results indicate that both doses of leptin decreased the number of marrow adipocytes in ob/ob mice by >20% (p adipocyte number with leptin treatment is accompanied by an increase in concentration of the apoptosis marker caspase-3 in bone marrow adipocytes and hematopoietic cells. Both leptin doses also significantly (p 30% compared with PBS-treated ob/ob mice. Leptin treatment increased whole body BMC by >30% in the ob/ob mice receiving the highest leptin dose. Leptin treatment provided no increase in bone formation, BMC, or BMD in normal, leptin-replete mice.

  3. Restoring the Architecture: A Rapid Clinical Perspective on Bone ...

    African Journals Online (AJOL)

    Osteoporosis is a highly prevalent and debilitating condition that contributes to the risk of fracture in both women and men. The current paper will provide a rapid clinical overview of the condition and the current pharmacotherapeutic approaches applied in its treatment. We close with a summary of novel treatment strategies ...

  4. Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis.

    Science.gov (United States)

    Osawa, Yusuke; Matsushita, Masaki; Hasegawa, Sachi; Esaki, Ryusaku; Fujio, Masahito; Ohkawara, Bisei; Ishiguro, Naoki; Ohno, Kinji; Kitoh, Hiroshi

    2017-12-01

    Achondroplasia (ACH) is one of the most common short-limbed skeletal dysplasias caused by gain-of-function mutations in the fibroblast growth factor receptors 3 (FGFR3) gene. Distraction osteogenesis (DO) is a treatment option for short stature in ACH in some countries. Although the patients with ACH usually show faster healing in DO, details of the newly formed bone have not been examined. We have developed a mouse model of DO and analyzed new bone regenerates of the transgenic mice with ACH (Fgfr3 ach mice) histologically and morphologically. We established two kinds of DO protocols, the short-DO consisted of 5days of latency period followed by 5days of distraction with a rate of 0.4mm per 24h, and the long-DO consisted of the same latency period followed by 7days of distraction with a rate of 0.3mm per 12h. The callus formation was evaluated radiologically by bone fill score and quantified by micro-CT scan in both protocols. The histomorphometric analysis was performed in the short-DO protocol by various stainings, including Villanueva Goldner, Safranin-O/Fast green, tartrate-resistant acid phosphatase, and type X collagen. Bone fill scores were significantly higher in Fgfr3 ach mice than in wild-type mice in both protocols. The individual bone parameters, including bone volume and bone volume/tissue volume, were also significantly higher in Fgfr3 ach mice than in wild-type mice in both protocols. The numbers of osteoblasts, as well as osteoclasts, around the trabecular bone were increased in Fgfr3 ach mice. Cartilaginous tissues of the distraction region rapidly disappeared in Fgfr3 ach mice compared to wild-type mice during the consolidation phase. Similarly, type X collagen-positive cells were markedly decreased in Fgfr3 ach mice during the same period. Fgfr3 ach mice exhibited accelerated bone regeneration after DO. Accelerated endochondral ossification could contribute to faster healing in Fgfr3 ach mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Fetal Bone Marrow-Derived Mesenchymal Stem/Stromal Cells Enhance Humanization and Bone Formation of BMP7 Loaded Scaffolds.

    Science.gov (United States)

    Shafiee, Abbas; Baldwin, Jeremy G; Patel, Jatin; Holzapfel, Boris M; Fisk, Nicholas M; Khosrotehrani, Kiarash; Hutmacher, Dietmar W

    2017-09-01

    Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis. X-ray radiography and micro computed tomography analyses showed enhanced bone formation in all BMP7 groups; however there was no difference after 2 months in bone formation between scaffolds seeded with fPL-MSC alone or combination of ECFC and fPL-MSC. Of interest, fBM-MSC showed the highest level of bone formation. Additionally, endochondral ossification contributed in generation of bone in fBM-MSC. Histological analysis showed the primary role of BMP in generation of cortical and trabecular bone, and the recruitment of hematopoietic cells to the scaffolds. Current in vivo engineered bone organs can potentially be used for drug screening or as models to study bone tissue development in combination with haematopoiesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite.

    Science.gov (United States)

    Kos, Marcin; Junka, Adam; Smutnicka, Danuta; Szymczyk, Patrycja; Gluza, Karolina; Bartoszewicz, Marzenna

    2015-07-01

    Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate. Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method. Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs. Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction. Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  7. Bacterial floc mediated rapid streamer formation in creeping flows

    CERN Document Server

    Hassanpourfard, Mahtab; Ghosh, Ranajay; Das, Siddhartha; Thundat, Thomas; Liu, Yang; Kumar, Aloke

    2015-01-01

    One of the central puzzles concerning the interaction of low Reynolds number (Re<<1) fluid transport with bacterial biomass is the formation of filamentous structures called streamers. In this manuscript, we report our discovery of a new kind of low Re bacterial streamers, which appear from pre-formed bacterial flocs. In sharp contrast to the biofilm-mediated streamers, these streamers form over extremely small timescales (less than a second). Our experiments, carried out in a microchannel with micropillars rely on fluorescence microscopy techniques to illustrate that floc-mediated streamers form when a freely-moving floc adheres to the micropillar wall and gets rapidly sheared by the background flow. We also show that at their inception the deformation of the flocs is dominated by recoverable large strains indicating significant elasticity. These strains subsequently increase tremendously to produce filamentous streamers. Interestingly, we find that these fully formed streamers are not static structure...

  8. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

    OpenAIRE

    McGee, Meghan E.; Maki, Aaron J.; Johnson, Steven E.; Lynne Nelson, O.; Robbins, Charles T.; Donahue, Seth W.

    2007-01-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. ...

  9. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects passed down ...

  10. CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling

    DEFF Research Database (Denmark)

    Abdallah, Basem M.; Figeac, Florence; Larsen, Kenneth H.

    2017-01-01

    % increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4(-/-) mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4(-/-) osteoblasts (OBs). Furthermore, Crmp4(-/-) OBs...

  11. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

    DEFF Research Database (Denmark)

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

    2004-01-01

    and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... was similar in HSD1(-/-) and Wt mice. In conclusion, our results suggest that 11betaHSD1 amplification of intracellular GC actions in mice may be required for bone marrow adipocyte formation, but not for bone formation. The clinical relevance of this observation remains to be determined....

  12. Heterotopic bone formation derived from multipotent stromal cells is not inhibited in aged mice.

    Science.gov (United States)

    Carbonneau, Cynthia L; Despars, Geneviève; Beaudry, Gaël Moquin; Benabdallah, Basma; Bouhanik, Saadallah; Dépôt, Josée; Moreau, Alain; Beauséjour, Christian M

    2014-08-01

    Decreased bone formation with age is believed to arise, at least in part, because of the influence of the senescent microenvironment. In this context, it is unclear whether multipotent stromal cell (MSC)-based therapies would be effective for the treatment of bone diseases. With the use of a heterotopic bone formation model, we investigated whether MSC-derived osteogenesis is impaired in aged mice compared with young mice. We found that bone formation derived from MSCs is not reduced in aged mice. These results are supported by the unexpected finding that conditioned media collected from ionizing radiation-induced senescent MSCs can stimulate mineralization and delay osteoclastogenesis in vitro. Overall, our results suggest that impaired bone formation with age is mainly cell-autonomous and provide a rationale for the use of MSC-based therapies for the treatment of bone diseases in the elderly. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation.

    Science.gov (United States)

    de Zegher, Francis; García Beltrán, Cristina; López-Bermejo, Abel; Ibáñez, Lourdes

    2017-11-07

    Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition. Longitudinal hand X-rays (0-4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; n = 17 untreated, n = 17 metformin-treated; age at the start of treatment 8 years) along with body composition (0-4 years, by DXA), hepatic fat, and abdominally subcutaneous and visceral fat (posttreatment, by MRI). The tempo of bone aging was accelerated in untreated girls (≈16% faster vs. chronological aging) and normal in metformin-treated girls (≈20% slower vs. untreated girls). Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat. The tempo of bone maturation was associated (R = 0.55; p fat. Metformin treatment in rapidly maturing girls with central adiposity normalized bone maturation. This normalization was accompanied by less central fat and was related closely to hepatic fat. © 2017 S. Karger AG, Basel.

  14. Abdominal Fat Is Associated With Lower Bone Formation and Inferior Bone Quality in Healthy Premenopausal Women: A Transiliac Bone Biopsy Study

    Science.gov (United States)

    Dempster, David W.; Recker, Robert R.; Lappe, Joan M.; Zhou, Hua; Zwahlen, Alexander; Müller, Ralph; Zhao, Binsheng; Guo, Xiaotao; Lang, Thomas; Saeed, Isra; Liu, X. Sherry; Guo, X. Edward; Cremers, Serge; Rosen, Clifford J.; Stein, Emily M.; Nickolas, Thomas L.; McMahon, Donald J.; Young, Polly; Shane, Elizabeth

    2013-01-01

    Context: The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. Objective: The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. Design: We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. Results: Body mass index (BMI) ranged from 20.1 to 39.2 kg/m2. Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm2/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = −0.50; P < .01) and bone formation rate (r = −0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI. Conclusions: At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation. PMID:23515452

  15. The effect of enamel matrix proteins and deproteinized bovine bone mineral on heterotopic bone formation.

    Science.gov (United States)

    Donos, Nikolaos; Kostopoulos, Lambros; Tonetti, Maurizio; Karring, Thorkild; Lang, Niklaus P

    2006-08-01

    To evaluate the osteoinductive potential of deproteinized bovine bone mineral (DBBM) and an enamel matrix derivative (EMD) in the muscle of rats. Sixteen rats were used in this study. The animals were divided in three groups. Group A: a pouch was created in one of the pectoralis profundis muscles of the thorax of the rats and DBBM particles (Bio-Oss) were placed into the pouch. Healing: 60 days. Group B: a small pouch was created on both pectoralis profundis muscles at each side of the thorax midline. In one side, a mixture of EMD (Emdogain) mixed with DBBM was placed into one of the pouches, whereas in the contralateral side of the thorax the pouch was implanted with DBBM mixed with the propylene glycol alginate (PGA--carrier for enamel matrix proteins of EMD). Healing: 60 days. Group C: the same procedure as group B, but with a healing period of 120 days. Qualitative histological analysis of the results was performed. At 60 days, the histological appearance of the DBBM particles implanted alone was similar to that of the particles implanted together with EMD or PGA at both 60 and 120 days. The DBBM particles were encapsulated into a connective tissue stroma and an inflammatory infiltrate. At 120 days, the DBBM particles implanted together with EMD or PGA exhibited the presence of resorption lacunae in some cases. Intramuscular bone formation was not encountered in any group. The implantation of DBBM particles alone, combined with EMD or its carrier (PGA) failed to exhibit extraskeletal, bone-inductive properties.

  16. Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

    Directory of Open Access Journals (Sweden)

    Yi-Hsiung Lin

    2017-11-01

    Full Text Available The natural pure compound obtusilactone A (OA was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs. OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

  17. Bone morphology of the femur and tibia captured by statistical shape modelling predicts rapid bone loss in acute spinal cord injury patients.

    Science.gov (United States)

    Varzi, Delaram; Coupaud, Sylvie A F; Purcell, Mariel; Allan, David B; Gregory, Jennifer S; Barr, Rebecca J

    2015-12-01

    After spinal cord injury (SCI), bone loss in the paralysed limbs progresses at variable rates. Decreases in bone mineral density (BMD) in the first year range from 1% (slow) to 40% (rapid). In chronic SCI, fragility fractures commonly occur around the knee, with significant associated morbidity. Osteoporosis treatments await full evaluation in SCI, but should be initiated early and targeted towards patients exhibiting rapid bone loss. The potential to predict rapid bone loss from a single bone scan within weeks of a SCI was investigated using statistical shape modelling (SSM) of bone morphology, hypothesis: baseline bone shape predicts bone loss at 12-months post-injury at fracture-prone sites. In this retrospective cohort study 25 SCI patients (median age, 33 years) were scanned at the distal femur and proximal tibia using peripheral Quantitative Computed Tomography at tibia mode 3, +1 SD) was associated with 9.4% additional 12-month tibial trabecular BMD loss. Baseline bone shape determined from a single bone scan is a valid imaging biomarker for the prediction of 12-month bone loss in SCI patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

    Science.gov (United States)

    Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

    2015-01-01

    We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

  19. BMP9-Induced Osteogenetic Differentiation and Bone Formation of Muscle-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Li Xiang

    2012-01-01

    Full Text Available Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9 in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.

  20. Chinese red yeast rice (Monascus purpureus-fermented rice promotes bone formation

    Directory of Open Access Journals (Sweden)

    Rabie Bakr

    2008-03-01

    Full Text Available Abstract Background Statin can induce the gene expression of bone morphogenetic protein-2. Red yeast rice (RYR, Hongqu, i.e. rice fermented with Monascus purpureus, contains a natural form of statin. This study demonstrates the effects of RYR extract on bone formation. Methods Bone defects were created in the parietal bones of two New Zealand white rabbits. In the test animal, two defects were grafted with collagen matrix mixed with RYR extract. In the control animal, two defects were grafted with collagen matrix alone. UMR 106 cell line was used to test RYR extract in vitro. In the control group, cells were cultured for three durations (24 hours, 48 hours and 72 hours without any intervention. In the RYR group, cells were cultured for the same durations with various concentrations of RYR extract (0.001 g/ml, 0.005 g/ml and 0.01 g/ml. Bicinchoninic acid (BCA assay, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and alkaline phosphatase (ALP assay were performed to measure total protein, mitochondrial activity and bone cell formation respectively. Results The test animal showed more formation of new bone in the defects than the control animal. RYR significantly increased the optical density in the MTT assay and ALP activity in vitro. Conclusion RYR extract stimulated new bone formation in bone defects in vivo and increased bone cell formation in vitro.

  1. Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles.

    Science.gov (United States)

    Visser, Jetze; Gawlitta, Debby; Benders, Kim E M; Toma, Selynda M H; Pouran, Behdad; van Weeren, P René; Dhert, Wouter J A; Malda, Jos

    2015-01-01

    The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 ± 2.5% vs. 39.5 ± 8.3% (mean ± standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Science.gov (United States)

    Handra-Luca, Adriana; Dumuis-Gimenez, Marie-Laure; Bendib, Mouna; Anagnostis, Panagiotis

    2015-01-01

    Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated. PMID:26697239

  3. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Directory of Open Access Journals (Sweden)

    Adriana Handra-Luca

    2015-01-01

    Full Text Available Thyroid heterotopic bone formation (HBF in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years. The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.. Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.. The number and size of HBFs (total: 28 ranged between 1 and 23/thyroid gland (one bilateral and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular. The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp. without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm, and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

  4. The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management.

    Science.gov (United States)

    Magrey, Marina N; Khan, Muhammad A

    2017-04-01

    The purpose of the study is to briefly review the molecular mechanisms that leads to structural damage in ankylosing spondylitis (AS), defined as new bone formation resulting in complete or incomplete ankylosis of the spine, and the impact of treatment with biologics to retard this process. The understanding of molecular mechanisms leading to new bone formation in AS has significantly improved but is still incomplete. Availability of biologics has greatly enhanced the treatment of patients with AS, but its impact on slowing the structural damage is still a matter of debate, although a few observational studies have shown that long term use of TNF-α blockers may slow radiographic progression. The availability of newer biologics targeting IL-17/1L23 has shown some promising results in slowing radiographic progression in AS. Although the availability of TNF-inhibitors has greatly enhanced the treatment options for patients with AS, their impact on slowing the structural damage is still not clearly established. However, preliminary results using newer biologics targeting IL-17/1L23 axis are more encouraging but longer follow-up is needed.

  5. Effect of Alendronate on Bone Formation during Tooth Extraction Wound Healing.

    Science.gov (United States)

    Tanoue, R; Koi, K; Yamashita, J

    2015-09-01

    Alendronate (ALN) is an antiresorptive agent widely used for the treatment of osteoporosis. Its suppressive effect on osteoclasts has been extensively studied. However, the effect of ALN on bone formation is not as clear as its effect on resorption. The objective was to determine the effect of short-term ALN on bone formation and tooth extraction wound healing. Molar tooth extractions were performed in mice. ALN, parathyroid hormone (PTH), or saline (vehicle control) was administered. PTH was used as the bone anabolic control. Mice were euthanized at 3, 5, 7, 10, and 21 d after extractions. Hard tissue healing was determined histomorphometrically. Neutrophils and lymphatic and blood vessels were quantified to evaluate soft tissue healing. Gene expression in the wounds was assessed at the RNA level. Furthermore, the vossicle bone transplant system was used to verify findings from extraction wound analysis. Alkaline phosphatase (ALP) was visualized in the vossicles to assess osteoblast activity. ALN exhibited no negative effect on bone formation. In intact tibiae, ALN increased bone mass significantly more than PTH did. Consistently, significantly elevated osteoblast numbers were noted. In the extraction sockets, bone fill in the ALN-treated mice was equivalent to the control. Genes associated with bone morphogenetic protein signaling, such as bmp2, nog, and dlx5, were activated in the extraction wounds of the ALN-treated animals. Bone formation in vossicles was significantly enhanced in the ALN versus PTH group. In agreement with this, ALN upregulated ALP activity considerably in vossicles. Neutrophil aggregation and suppressed lymphangiogenesis were evident in the soft tissue at 21 d after extraction, although gross healing of extraction wounds was uneventful. Bone formation was not impeded by short-term ALN treatment. Rather, short-term ALN treatment enhanced bone formation. ALN did not alter bone fill in extraction sockets. © International & American

  6. Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.

    Science.gov (United States)

    Blouin, Stéphane; Fratzl-Zelman, Nadja; Glorieux, Francis H; Roschger, Paul; Klaushofer, Klaus; Marini, Joan C; Rauch, Frank

    2017-09-01

    In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p V Ct and Cn bone (+171%, p V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  7. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    Science.gov (United States)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  8. Bone density of the midpalatal suture 7 months after surgically assisted rapid palatal expansion in adults.

    Science.gov (United States)

    Petrick, Silvia; Hothan, Thorsten; Hietschold, Volker; Schneider, Matthias; Harzer, Winfried; Tausche, Eve

    2011-04-01

    The aims of this study were to analyze changes in bone density of the midpalatal suture after surgically assisted rapid palatal expansion (SARPE) with the bone-borne Dresden Distractor (DD; ITU, Dresden, Germany) via computed tomography (CT) and to compare of preoperative surgical findings with a control group. Sixteen adult patients (mean age 24.5 years) underwent axial CT scans before and 7 months after SARPE. CT image fusion was performed for the midpalatal suture bone. Sixty-six controls (mean age 25.7 years) served for comparing age-related bone density. Bone structure and density were assessed in the coronal plane at the anterior, median, and posterior levels. Highest density was found in the posterior part (1046 Hounsfield units [HU]) before expansion. Seven months after SARPE, bone density was 48% (anterior), 53% (median), and 75% (posterior) compared with preoperative values. The control group showed fairly equal Hounsfield units (889 HU to 900 HU) in all parts. Seven months after SARPE, the midpalatal suture's density achieves just one half to three quarters of the pretreatment values. To maintain the resistance against forces from the unsplit posterior part, the retention time should be lengthened. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. [Benign fibro-osseous lesions of the craniofacial complex with aneurysmal bone cyst formation].

    Science.gov (United States)

    Geraldo, Ana Filipa; Mendes Dos Santos, Carolina; Tavares, Joana; Fernandes Sousa, Rita; Campos, Alexandre; Farias, João Paulo; Pimentel, José; Guedes Campos, Jorge

    2012-01-01

    Aneurysmal bone cyst are controversial osteolytic benign expansive lesions which occur more frequently in the metaphysis of long bones and spine. They are classified as primary or secondary lesions depending on the presence or absence of an associated bone pathology. The engraftment of aneurysmal bone cyst onto benign fibro-osseous lesions is established. However, in the craniofacial complex this combined lesion is rare.The authors present two histologically proven uncommon cases of benign fibro-osseous lesions (fibrous dysplasia and juvenile psammomatoid ossifying fibroma) with aneurysmal bone cyst formation, emphasizing the imaging characteristics of this hybrid entities.

  10. Prevention of fibrous layer formation between bone and adhesive bone cement: in vivo evaluation of bone impregnation with 4-META/MMA-TBB cement.

    Science.gov (United States)

    Sakai, T; Morita, S; Shinomiya, K; Watanabe, A; Nakabayashi, N; Ishihara, K

    2000-10-01

    We have studied a new adhesive bone cement, that consists of 4-methacryloyloxyethyl trimellitate anhydride (4-META) and methylmethacrylate (MMA) as monomers, tri-n-butyl borane (TBB) as the initiator, and polymethylmethacrylate powder (4-META/MMA-TBB cement). This cement has shown remarkable adhesive properties to bone in vitro. In this study, we assessed the interface in vivo periodically. The femora of rabbits were fenestrated and filled with either the 4-META/MMA-TBB cement or a conventional polymethylmethacrylate cement. The animals were killed after 1, 4, 12, and 24 weeks to analyze the interface by optical microscopy and transmission electron microscopy. Optical microscopic examinations showed that the cured 4-META/MMA-TBB adhesive cement bonded to bone directly for 24 weeks, whereas a fibrous tissue layer was observed between the bone and cured conventional cement at 12 weeks after the operation. The transmission electron microscopy views of 4-META/MMA-TBB cement bonded to bone demonstrated a unique "hybridized bone" with the cement in the subsurface of the substrate in every case. The formation of the hybridized bone indicates the bonding mechanism of the adhesive cement to bone, which prevents the fibrosis intervention between bone and cement. These results suggest that the biomechanical and adhesive properties of 4-META/MMA-TBB cement make it a useful bone-bonding agent in orthopedic surgery. Copyright 2000 John Wiley & Sons, Inc.

  11. A rapid procedure for routine double staining of cartilage and bone in fetal and adult animals.

    Science.gov (United States)

    Kimmel, C A; Trammell, C

    1981-09-01

    A simple, rapid procedure for dual staining of cartilage and bone in rodents, particularly in late gestation, has been developed for routine use. The procedure involves rapid, complete skinning of fresh eviscerated specimens following a 30 sec immersion in a 70 C water bath. The unfixed specimen is stained in a mixture of 0.14% Alcian blue and 0.12% alizarin red S in ethanol and glacial acetic acid. Specimens are then macerated in 2% KOH, cleared and hardened in 1:1 glycerin and distilled water, and stored in pure glycerin. Rapid staining of cartilage only is done in a mixture of 0.08% Alcian blue, glacial acetic acid, and ethanol, with subsequent maceration, clearing, and hardening as in the double staining procedure. Rapid staining of bone only, concurrent with maceration of soft tissue, can be done by placing fresh, unskinned specimens in a diluted mixture of alizarin red S in 2% KOH, with subsequent clearing and hardening in 1:1 distilled water and glycerin. Good quality fetal specimens can be prepared for examination by any of these procedures in a minimum of 11/2-2 days as compared to a minimum of 4-5 days for other procedures. Double stained specimens can be examined for abnormalities of the cartilage as well as bone.

  12. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    Science.gov (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  13. Effects of vascular formation during alveolar bone process morphogenesis in mice.

    Science.gov (United States)

    An, Seo-Young; Lee, Ye-Ji; Neupane, Sanjiv; Jun, Jong-Hwa; Kim, Ji-Youn; Lee, Youngkyun; Choi, Karp-Shik; An, Chang-Hyeon; Suh, Jo-Young; Shin, Hong-In; Sohn, Wern-Joo; Kim, Jae-Young

    2017-10-01

    The alveolar bone process is the thickened ridge of bone that bears the teeth and is known to have dynamic functional interactions with surrounding tissues. However, the detailed morphological changes that occur during alveolar bone process development and the underlying molecular mechanisms behind this morphogenesis have not been elucidated. In this study, we examined the detailed morphological changes of the alveolar bone process during mouse development using HE and MTC staining. In addition, we evaluated the precise localization pattern of various signaling molecules involved in blood vessel formation including CD31, α-SMA, VEGF, periostin, and TGF-β. Innervation of the alveolar bone process was examined following injection of the nerve terminal dye AM1-43. The morphological and immunohistochemical data suggested that there is an intimate relationship between alveolar bone process development and blood vessel formation. To more closely examine the role of blood vessels in alveolar bone process formation, we microinjected mice with a clinically available anti-VEGF antibody, bevacizumab, at PN5 and analyzed the effects 5 days later. Compared to the control animals, anti-VEGF treated animals showed a disruption of the integration of bony tissues to form the alveolar bone process structures, which should contain the periodontal ligaments. Based on these data, we conclude that specific morphogenesis of the alveolar bone process is closely associated with blood vessel formation.

  14. Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.

    Directory of Open Access Journals (Sweden)

    Jochen Schulze

    Full Text Available Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2 is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2 results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders.

  15. Biofilm formation by staphylococci on fresh, fresh-frozen and processed human and bovine bone grafts.

    Science.gov (United States)

    Clauss, M; Tafin, U F; Bizzini, A; Trampuz, A; Ilchmann, T

    2013-01-30

    Biofilm formation is a multi-step process influenced by surface properties. We investigated early and mature biofilm of Staphylococcus aureus on 4 different biological calcium phosphate (CaP) bone grafts used for filling bone defects. We investigated standardised cylinders of fresh and fresh-frozen human bone grafts were harvested from femoral heads; processed humanand bovine bone grafts were obtained preformed. Biofilm formation was done in tryptic soy broth (TSB) using S. aureus (ATCC 29213) with static conditions. Biofilm density after 3 h (early biofilm) and 24 h (mature biofilm) was investigated by sonication and microcalorimetry. After 3 h, bacterial density was highest on fresh-frozenandfresh bone grafts. After 24 h, biofilm density was lowest on freshbone grafts (p  0.05). The lowest increase in bacterial density was detected on fresh bone grafts (p bone grafts showed minor structural differences in architecture but marked differences concerning serum coverage and the content of bone marrow, fibrous tissue and bone cells. These variations resulted in a decreased biofilm density on freshand fresh-frozenbone grafts after 24 h, despite an increased early biofilm formation and might also be responsible for the variations in colony morphology (small colonies). Detection of small colony variants by microcalorimetry might be a new approach to improve the understanding of biofilm formation.

  16. Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role in bone growth and remodeling.

    Science.gov (United States)

    McGregor, Narelle E; Poulton, Ingrid J; Walker, Emma C; Pompolo, Sueli; Quinn, Julian M W; Martin, T John; Sims, Natalie A

    2010-03-01

    Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF or CLC, but not NP, significantly inhibited mineralization and osterix mRNA levels. Twelve-week-old male CNTF ( -/- ) mice demonstrated reduced femoral length, cortical thickness, and periosteal circumference; but femoral trabecular bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not significantly different from wild-type, indicating a unique role for CNTF in bone growth in male mice. In contrast, female CNTF ( -/- ) femora were of normal width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular thickness were all increased. Female CNTF ( -/- ) tibiae also demonstrated high osteoblast number and mineral apposition rate compared to wild-type littermates, and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in bone and plays a unique role in female mice as an inhibitor of trabecular bone formation and in male mice as a stimulus of cortical growth.

  17. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone wi...

  18. Bone formation in cranial, mandibular, tibial and iliac bone grafts in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Talsnes, O

    1995-01-01

    Several studies have suggested that grafts from membranous derived bone (e.g., calvarial grafts) retain their volume better than those from endochondral derived bone (e.g., iliac bone grafts). Increased osteogenesis in grafts of the former type has been offered as the explanation. However, simple...

  19. Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.

    Science.gov (United States)

    Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

    2006-05-01

    Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (Phibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (Phibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the

  20. In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

    Science.gov (United States)

    Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

    2016-08-01

    Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

  1. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model

    Science.gov (United States)

    Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2011-01-01

    Abstract Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29+, CD44+ and CD166+ after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. PMID

  2. Evaluation of opening pattern and bone neoformation at median palatal suture area in patients submitted to surgically assisted rapid maxillary expansion (SARME through cone beam computed tomography

    Directory of Open Access Journals (Sweden)

    Daniel Gomes SALGUEIRO

    2015-08-01

    Full Text Available AbstractSurgically assisted rapid maxillary expansion (SARME is the treatment of choice to adult patients even with severe transversal maxillary discrepancies. However, the adequate retention period to achieve the bone remodeling, thus assuring treatment stability, is controversial.Objective To evaluate the opening pattern and bone neoformation process at the midpalatal suture in patients submitted to surgically assisted (SARME through cone beam computed tomography (CBCT.Material and Methods Fourteen patients were submitted to SARME through subtotal Le Fort I osteotomy. Both the opening pattern and the mean bone density at midpalatal suture area to evaluate bone formation were assessed pre- and post-operatively (15, 60 and 180 days through CBCT.Results Type I opening pattern (from anterior to posterior nasal spine occurred in 12 subjects while type II opening pattern (from anterior nasal spine to transverse palatine suture occurred in 2 individuals. The 180-day postoperative mean (PO 180 of bone density value was 49.9% of the preoperative mean (Pre value.Conclusions The opening pattern of midpalatal suture is more related to patients’ age (23.9 years in type I and 33.5 years in type II and surgical technique. It was not possible to observe complete bone formation at midpalatal suture area at the ending of the retention period studied (180 days.

  3. Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

    Science.gov (United States)

    Hoch, Allison I; Duhr, Ralph; Di Maggio, Nunzia; Mehrkens, Arne; Jakob, Marcel; Wendt, David

    2017-12-01

    Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation

    NARCIS (Netherlands)

    Scheijen, B.; Bronk, M.; Meer, T. van der; Bernards, R.A.

    2003-01-01

    Longitudinal bone growth results from endochondral ossification, a process that requires proliferation and differentiation of chondrocytes. It has been shown that proper endochondral bone formation is critically dependent on the retinoblastoma family members p107 and p130. However, the precise

  5. Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

    Science.gov (United States)

    Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

    2012-09-01

    OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

  6. Stretch force guides finger-like pattern of bone formation in suture

    Science.gov (United States)

    Kou, Xiao-Xing; Zhang, Ci; Zhang, Yi-Mei; Cui, Zhen; Wang, Xue-Dong; Liu, Yan; Liu, Da-Wei; Zhou, Yan-Heng

    2017-01-01

    Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction

  7. Stretch force guides finger-like pattern of bone formation in suture.

    Directory of Open Access Journals (Sweden)

    Bo-Hai Wu

    Full Text Available Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling

  8. Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

    Directory of Open Access Journals (Sweden)

    Takenobu Katagiri, PhD

    2015-05-01

    Full Text Available Bone morphogenetic protein (BMP was originally discovered by Marshall Urist a half century ago following the observation of a unique activity that induced heterotopic bone formation in skeletal muscle tissue. The molecular mechanisms underlying the induction of heterotopic bone formation in skeletal muscle by BMPs were elucidated through the purification and molecular cloning of BMPs and identification of their functional receptors and downstream effectors, as well as from genetic disorders related to BMP activity. BMPs are important regulators of not only skeletal development and regeneration but also the homeostasis of normal skeletal muscle mass. There is still much to learn about the physiology and pathology at the interface of BMPs and skeletal muscle.

  9. (18)F-fluoride positron emission tomography measurements of regional bone formation in hemodialysis patients with suspected adynamic bone disease.

    Science.gov (United States)

    Frost, Michelle L; Compston, Juliet E; Goldsmith, David; Moore, Amelia E; Blake, Glen M; Siddique, Musib; Skingle, Linda; Fogelman, Ignac

    2013-11-01

    (18)F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 μm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of (18)F-PET as a diagnostic tool for identifying CKD patients with ABD.

  10. The effect of semelil (angipars® on bone resorption and bone formation markers in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Hasani-Ranjbar Shirin

    2012-12-01

    Full Text Available Abstract Background and purpose of the study Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars® for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. Methods In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100 mg of Angipars® twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months. Result 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8 ± 6.2 and 7.5 ± 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-α. Only urine creatinine level significantly changed between two groups after 3 month of treatment (p-value: 0.029 Conclusion In conclusion, the findings of this study indicate that Semelil (Angipars® had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered.

  11. The Efect of Semelil (AngiparsW on Bone Resorption and Bone Formation Markers in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Shirin Hasani-Ranjbar

    2012-01-01

    Full Text Available Background and purpose of the study: Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of AngiparsW for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need toevaluate the effect of this new drug on different organs including bone resorption and bone formation markers.Methods: In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects wererandomly divided into intervention and control groups. Subjects of intervention group received 100 mg of AngiparsW twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months.Result: 31 patients in study group and 30 patients in control group finished the study. The mean age of the studypopulation and the mean disease duration was respectively 51.8 ± 6.2 and 7.5 ± 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-α. Only urine creatinine level significantly changed between two groups after 3 month of treatment (pvalue:0.029Conclusion: In conclusion, the findings of this study indicate that Semelil (AngiparsW had no beneficial or harmfuleffects on bone. It might be other effects of this new component on bone turnover process which need morestudies and more time to be discovered.

  12. High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity.

    Science.gov (United States)

    Lecka-Czernik, B; Stechschulte, L A; Czernik, P J; Dowling, A R

    2015-07-15

    Obesity is generally recognized as a condition which positively influences bone mass and bone mineral density (BMD). Positive effect of high body mass index (BMI) on bone has been recognized as a result of increased mechanical loading exerted on the skeleton. However, epidemiologic studies indicate that obesity is associated with increased incidence of fractures. The results presented here offer a new perspective regarding the mechanisms which may be responsible for the increase of bone mass and concurrent decrease in bone quality. Two groups of 12 week old C57BL/6 males were fed either high fat diet (HFD) or regular diet (RD) for 11 weeks. Metabolic profile, bone parameters and gene expression were assessed in these groups at the end of the experiment. Additionally, bone status was evaluated in a third group of 12 week old animals corresponding to animals at the start of the feeding period. Administration of HFD resulted in development of a diet-induced obesity (DIO), glucose intolerance, alteration in energy metabolism, and impairment in WAT function, as compared to the age-matched control animals fed RD. The expression of adiponectin, FABP4/aP2, DIO2 and FoxC2 were decreased in WAT of DIO animals, as well as transcript levels for IGFBP2, the cytokine regulating both energy metabolism and bone mass. At the end of experiment, DIO mice had higher bone mass than both control groups on RD, however they had decreased bone formation, as assessed by calcein labeling, and increased marrow adipocyte content. This study suggests that the bone mass acquired in obesity is a result of a two-phase process. First phase would consist of either beneficial effect of fat expansion to increase bone mass by increased mechanical loading and/or increased production of bone anabolic adipokines and/or nutritional effect of fatty acids. This is followed by a second phase characterized by decreased bone formation and bone turnover resulting from development of metabolic impairment

  13. Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

    Science.gov (United States)

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping

    2014-10-01

    A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities

  14. Effect of autologous bone marrow stromal cell seeding and bone morphogenetic protein-2 delivery on ectopic bone formation in a microsphere/poly(propylene fumarate) composite.

    Science.gov (United States)

    Kempen, Diederik H R; Kruyt, Moyo C; Lu, Lichun; Wilson, Clayton E; Florschutz, Anthony V; Creemers, Laura B; Yaszemski, Michael J; Dhert, Wouter J A

    2009-03-01

    A biodegradable microsphere/scaffold composite based on the synthetic polymer poly(propylene fumarate) (PPF) holds promise as a scaffold for cell growth and sustained delivery vehicle for growth factors for bone regeneration. The objective of the current work was to investigate the in vitro release and in vivo bone forming capacity of this microsphere/scaffold composite containing bone morphogenetic protein-2 (BMP-2) in combination with autologous bone marrow stromal cells (BMSCs) in a goat ectopic implantation model. Three composites consisting of 0, 0.08, or 8 microg BMP-2 per mg of poly(lactic-co-glycolic acid) microspheres, embedded in a porous PPF scaffold, were combined with either plasma (no cells) or culture-expanded BMSCs. PPF scaffolds impregnated with a BMP-2 solution and combined with BMSCs as well as empty PPF scaffolds were also tested. The eight different composites were implanted subcutaneously in the dorsal thoracolumbar area of goats. Incorporation of BMP-2-loaded microspheres in the PPF scaffold resulted in a more sustained in vitro release with a lower burst phase, as compared to BMP-2-impregnated scaffolds. Histological analysis after 9 weeks of implantation showed bone formation in the pores of 11/16 composites containing 8 microg/mg BMP-2-loaded microspheres with no significant difference between composites with or without BMSCs (6/8 and 5/8, respectively). Bone formation was also observed in 1/8 of the BMP-2-impregnated scaffolds. No bone formation was observed in the other conditions. Overall, this study shows the feasibility of bone induction by BMP-2 release from microspheres/scaffold composites.

  15. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  16. Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

    Science.gov (United States)

    Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

    2017-10-10

    Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our

  17. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

    Directory of Open Access Journals (Sweden)

    Patricia Ros-Tárraga

    2016-09-01

    Full Text Available This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared. The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung as a result of degradation products being released.

  18. Effect of low gravity on calcium metabolism and bone formation (L-7)

    Science.gov (United States)

    Suda, Tatsuo

    1993-01-01

    Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

  19. Effect of icariin on bone formation during distraction osteogenesis in the rabbit mandible.

    Science.gov (United States)

    Wei, H; Zili, L; Yuanlu, C; Biao, Y; Cheng, L; Xiaoxia, W; Yang, L; Xing, W

    2011-04-01

    The aim of this study was to evaluate the effect of icariin on bone formation during mandibular distraction. 40 Rabbits were randomly divided into experimental and control groups. Mandibular distraction was performed 5 days after unilateral mandibular osteotomy using a custom-made external distractor at a rate of 0.5mm/12h for 10 days. From the first day of distraction, icariin (2.5mg/kg · day) was orally administered to the experimental group and placebo to the controls. 10 Rabbits were killed at the end of weeks 2 and 4 of the consolidation phase. The distracted hemimandible was harvested and newly formed bone was evaluated by soft radiography, histology and bone histomorphometry. Regenerated bone was evaluated for bone mineral density by dual-energy X-ray absorptiometry. The experimental group had fewer radiolucent areas on soft radiography. Bone mineral density of regenerated bone was higher in the experimental than in the control group at 2 and 4 weeks. At 4 weeks, the experimental group had greater volumes of new bone, higher trabecular number, and less trabecular separation than the controls. Oral administration of icariin could promote bone formation during mandibular distraction osteogenesis and might be a promising method for shortening the course of distraction osteogenesis. Copyright © 2010. Published by Elsevier Ltd.

  20. Rapid neutron capture process in supernovae and chemical element formation

    NARCIS (Netherlands)

    Baruah, Rulee; Duorah, Kalpana; Duorah, H. L.

    2009-01-01

    The rapid neutron capture process (r-process) is one of the major nucleosynthesis processes responsible for the synthesis of heavy nuclei beyond iron. Isotopes beyond Fe are most exclusively formed in neutron capture processes and more heavier ones are produced by the r-process. Approximately half

  1. Experimental Study of Cloud Formation from Rapidly Opened Containers

    Energy Technology Data Exchange (ETDEWEB)

    Wooldridge, C.E. [Stanford Research Institute; Amaro, A.J. [Stanford Research Institute; Kier, R.J. [Stanford Research Institute

    1969-08-01

    This report presents the results of an experimental study of droplet size emanating from a rapidly-opened container of volatile liquid, of the internal dynamics of the cavitation process inside such a container, & of the evaporation time of propane drops.

  2. Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

    Science.gov (United States)

    Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

    2013-01-01

    Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

  3. Changes of bone formation markers osteocalcin and bone-specific alkaline phosphatase in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Lumachi, Franco; Ermani, Mario; Camozzi, Valentina; Tombolan, Valeria; Luisetto, Giovanni

    2009-09-01

    The relationship between bone formation markers osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) and age in postmenopausal women was investigated. Forty-eight osteoporotic women (median age 62, range 49-76 years) were enrolled in the study. There were 17 (35%) patients aged 49-59 years (Group A), and 31 (65%) patients aged over 59 years (Group B). Parathyroid hormone, calcium, and creatinine serum levels did not differ significantly between groups. Compared with Group A, patients in Group B had higher levels of both OC (28.5 +/- 17.8 versus 46.2 +/- 19.3 ng/mL; P= 0.003) and bALP (57.3 +/- 12.4 versus 66.4 +/- 8.7 U/L; P= 0.005). A significant relationship between age and both OC (R= 0.49, P= 0.002) and bALP (R= 0.41, P= 0.009) was found only in Group B, but there was no relationship with bone mineral density. In conclusion, in postmenopausal women the increase of bone formation markers later in life may be an expression of increased bone turnover, which is partially the cause of osteoporosis.

  4. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

    DEFF Research Database (Denmark)

    Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette

    2015-01-01

    CONTEXT: Recent studies indicate that glucagon-like peptide 1 (GLP-1) regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. OBJECTIVE: To investigate the role of GLP-1 RAs on bone formation and weight loss induced...... bone mass reductions. DESIGN: Randomized control study. SETTING: Out-patient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), age 46±2 years. INTERVENTION: After a low-calorie diet-induced 12% weight loss, participants were randomized to treatment...... with or without administration of the GLP-1 RA liraglutide (1.2mg/day) for 52 weeks. In case of weight gain, up to two meals per day could be substituted with a low-calorie diet product in order to maintain the weight loss. MAIN OUTCOME MEASURES: Total, pelvic and arm-leg bone mineral content (BMC) and bone...

  5. Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model?

    Science.gov (United States)

    Walsh, William R; Pelletier, Matthew H; Bertollo, Nicky; Christou, Chris; Tan, Chris

    2016-11-01

    Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA(®) Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies.

  6. Effect of dual treatment with SDF-1 and BMP-2 on ectopic and orthotopic bone formation.

    Directory of Open Access Journals (Sweden)

    Chang-Hwan Lee

    Full Text Available The potent stem cell homing factor stromal cell-derived factor-1 (SDF-1 actively recruits mesenchymal stem cells from circulation and from local bone marrow. It is well established that bone morphogenetic protein-2 (BMP-2 induces ectopic and orthotopic bone formation. However, the exact synergistic effects of BMP-2 and SDF-1 in ectopic and orthotopic bone regeneration models have not been fully investigated. The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.Various doses of SDF-1 were loaded onto collagen sponges with or without BMP-2.These sponges were implanted into subcutaneous pockets and critical-size calvarial defects in C57BL/6 mice. The specimens were harvested 4 weeks post-surgery and the degree of bone formation in specimens was evaluated by histomorphometric and radiographic density analyses. Osteogenic potential and migration capacity of mesenchymal cells and capillary tube formation of endothelial cells following dual treatment with SDF-1 and BMP-2 were evaluated with in vitro assays.SDF-1-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance BMP-2-induced ectopic and orthotopic bone regeneration. In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone.These findings imply that sequence-controlled application of SDF-1 and BMP-2 must be further investigated for the enhancement of robust osteogenesis in bone defects.

  7. A composite material model for improved bone formation.

    Science.gov (United States)

    Scaglione, Silvia; Lazzarini, Erica; Ilengo, Cristina; Quarto, Rodolfo

    2010-10-01

    The combination of synthetic polymers and calcium phosphates represent an improvement in the development of scaffolds for bone-tissue regeneration. Ideally, these composites provide both mechanically and architecturally enhanced performances; however, they often lack properties such as osteoconductivity and cell bioactivation. In this study we attempted to generate a composite bone substitute maximizing the available osteoconductive surface for cell adhesion and activity. Highly porous scaffolds were prepared through a particulate leaching method, combining poly-ε-caprolactone (PCL) and hydroxyapatite (HA) particles, previously coated with a sucrose layer, to minimize their embedding by the polymer solution. Composite performances were evaluated both in vitro and in vivo. In PCL-sucrose-coated HA samples, the HA particles were almost completely exposed and physically distinct from the polymer mesh, while uncoated control samples showed ceramic granules massively covered by the polymer. In vivo results revealed a significant extent of bone deposition around all sucrose-coated HA granules, while only parts of the control uncoated HA granules were surrounded by bone matrix. These findings highlight the possibility of generating enhanced osteoconductive materials, basing the scaffold design on physiological and cellular concepts. Copyright © 2010 John Wiley & Sons, Ltd.

  8. Reconstruction of Frontal Bone With Custom-Made Prosthesis Using Rapid Prototyping.

    Science.gov (United States)

    Florentino, Vinícius Gabriel Barros; Mendonça, Diego Santiago de; Bezerra, Ariel Valente; Silva, Leonardo de Freitas; Pontes, Rafael Figueirêdo; Melo, Carlos Vinícius Mota de; Mello, Manoel de Jesus Rodrigues; de Aguiar, Andréa Silvia Walter

    2016-06-01

    Frontal bone fracture treatment is still an issue of research in craniofacial surgery and neurosurgery. The aims of the treatment are to reduce the complication risks and to keep the aesthetic of the face. Before the management of this fracture type, it is necessary to consider the permanence or not of the frontal sinus function. Rapid prototyping has been an aid tool on planning and simulation of the surgical procedure, improving the diagnostic quality and the implant manufacture, beyond reducing the operative time. Among the used materials on treatment of these fractures, titanium mesh shows large versatility and ease of handling. Poly(methyl methacrylate) has been used in defects of partial thickness or irregularities on cranial surface. The aim of this study is to report a case of a patient presenting sequelae of large fracture of anterior wall of frontal bone, treated by a titanium mesh associated with the customized poly(methyl methacrylate) implant from the rapid prototyping. It could be concluded that the use of this technique showed itself effective on patient treatment, and rapid prototyping demonstrated being a valuable tool showing predictable and satisfactory results.

  9. Effect of coating Straumann Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation.

    Science.gov (United States)

    Mrozik, Krzysztof Marek; Gronthos, Stan; Menicanin, Danijela; Marino, Victor; Bartold, P Mark

    2012-06-01

    Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann Bone Ceramic coated with Straumann Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared

  10. Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2014-09-01

    Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

  11. Strontium-containing apatite/polylactide composites enhance bone formation in osteopenic rabbits.

    Science.gov (United States)

    Luo, Xiaoman; Barbieri, Davide; Duan, Rongquan; Yuan, Huipin; Bruijn, Joost D

    2015-10-01

    Strontium (Sr) has been shown to favor bone formation and is used clinically to treat osteoporosis. We have previously reported that Sr addition in apatite/polylactide composites could enhance the BMP-induced bone formation around implants at ectopic site in healthy animals. In this study we aimed to investigate the effectiveness of Sr addition on the local bone formation in osteoporosis. Apatite/polylactide composite granules with different Sr content were loaded with equal amount of rhBMP-2 and implanted intramuscularly in healthy rabbits (Con) and rabbits that received bilateral ovariectomy and daily injection of glucocorticoid (OP) for 12 weeks. The potential effect of Sr on the final volume of BMP-induced bone in both groups was investigated histologically and histomorphometrically. The de novo bone formed in OP implants was significantly less than in Con group when the implants contained no Sr, indicating that the BMP-induced osteogenesis was impaired in OP animals. Sr substitution as low as 0.5 mol% in apatite increased the bone volume in OP implants to levels comparable to that in the Con group, indicating a positive effect of Sr addition on the local bone formation in OP animals. In addition, more adipose tissue formed in parallel with the appearance of cartilage tissue in OP implants, suggesting that the differentiation potential of stem cell in OP animals may have shifted towards adipogenesis and chondrogenesis. From these results, we conclude that the use of Sr addition to enhance the bone growth surrounding implants in osteoporosis merits further study. The impaired bone healing capacity of osteoporotic patients might result in poor osteointegration and surgical failure in case implants are placed. In this study we aimed to enhance the bone formation around implants under such scenario by adding strontium as the stimulus. Different from other studies, the samples were loaded with rhBMP-2 and implanted at an ectopic site (spinal muscles of New Zealand

  12. Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation

    NARCIS (Netherlands)

    van de Belt, H; Neut, D; Schenk, W; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    2000-01-01

    We measured the formation of a Staphylococcus aureus biofilm in vitro on unloaded and gentamicin-loaded bone cements (CMW3 and Palaces R) and related the formation to antibiotic release rates. All experiments were done in triplicate. Microbial growth on gentamicin-loaded cements occurred despite the

  13. A Computational Analysis of Bone Formation in the Cranial Vault in the Mouse

    Directory of Open Access Journals (Sweden)

    Chanyoung eLee

    2015-03-01

    Full Text Available Bones of the cranial vault are formed by the differentiation of mesenchymal cells into osteoblasts on a surface that surrounds the brain, eventually forming mineralized bone. Signaling pathways causative for the cell differentiation include the actions of extracellular proteins driven by information from genes. We assume that the interaction of cells and extracellular molecules which are associated with cell differentiation can be modeled using Turing’s reaction-diffusion model, a mathematical model for pattern formation controlled by two interacting molecules (activator and inhibitor. In this study we hypothesize that regions of high concentration of an activator develop into primary centers of ossification, the earliest sites of cranial vault bone. In addition to the Turing model, we use another diffusion equation to model a morphogen (potentially the same as the morphogen associated with formation of ossification centers associated with bone growth. These mathematical models were solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data showing skull bone formation in mouse at different embryonic days in both of normal and defect conditions. The results show that the relative locations of the five ossification centers that form in our model occur at the same position as those identified in experimental data. As bone grows from these ossification centers, sutures form between the bones.

  14. Rapid Formation of Cerebral Microbleeds after Carotid Artery Stenting

    Directory of Open Access Journals (Sweden)

    Kousuke Kakumoto

    2012-03-01

    Full Text Available Background: Recent studies reported that cerebral microbleeds (CMBs, i.e. small areas of signal loss on T2*-weighted gradient-echo (GE imaging, could develop rapidly after acute ischemic stroke. We hypothesized that CMBs rapidly emerge after carotid artery stenting (CAS. Objective: We investigated the frequency of and predisposing factors for CMBs after CAS. Methods: We retrospectively examined MRI before and after CAS in 88 consecutive patients (average age: 71.7 ± 7.2 years, average rates of carotid stenosis: 72.6 ± 12.8% who underwent CAS for carotid artery stenosis between March 1, 2009, and September 30, 2010. We defined new CMBs as signal losses that newly appeared on the follow-up GE. We examined the association of new CMBs with demographics, risk factors, and baseline MBs. Results: Among 88 patients, 18 (20.5% had CMBs initially, and 7 (8.0% developed new CMBs right after CAS. New CMBs appeared on the same side of CAS in all of the 7 patients. New CMBs appeared significantly more frequently in the CMB-positive group than in the CMB-negative one (22% vs. 4%, p = 0.03 on the pre-CAS MRI. Multivariate analysis also revealed that the presence of CMBs before CAS was an independent predictor of new development of CMBs after CAS (odds ratio: 8.09, 95% confidence interval: 1.39–47.1. Conclusion: CMBs can develop rapidly after CAS, especially in patients with pre-existing CMBs. Since the existence of CMBs prior to CAS suggests a latent vascular damage which is vulnerable to hemodynamic stress following CAS, particular attention should be paid to the prevention of intracerebral hemorrhage due to hyperperfusion after CAS.

  15. Sterile neutrinos and the rapid formation of supermassive black holes

    Science.gov (United States)

    Richter, M. C.; Tupper, G. B.; Viollier, R. D.

    2008-11-01

    The most massive black holes, lurking at the centers of large galaxies, must have formed less than a billion years after the big bang, as they are visible today in the form of bright quasars at redshift z gtrsim 6[1]. Their early appearance is mysterious, because the radiation pressure, generated by infalling ionized baryonic matter, inhibits the rapid growth of these black holes from stellar-mass black holes [2]. Here we show that the supermassive black holes may, instead, form timeously through the accretion of degenerate sterile neutrino dark matter onto stellar-mass black holes [3].

  16. Callus formation in bone fractures combined with brain injury in rat

    Directory of Open Access Journals (Sweden)

    Yu-Ping Chen

    2017-01-01

    Full Text Available Objective: The objective of this study was to determine the speed of bony union and the serum levels of biomarkers in the setting of bone fractures combined with brain injury. Materials and Methods: In this study, Sprague–Dawley rats were randomized into four groups: sham, brain injury, bone fracture, and bone fracture plus brain injury groups. The serum levels of biochemical markers, namely, nerve growth factor (NGF, Wnt-3a, Dickkopf-related protein-1, receptor-activator of NF-κB ligand, and adrenocorticotropic hormone (ACTH, were measured on the days 1, 3, 7, and 14 following injury. Bony union was evaluated using radiographs every week for 6 weeks. Results: Compared with the brain injury group and bone fracture group, the radiographs of the bone fracture plus brain injury group revealed enhanced callus formations in week 2. From week 3, the callus formation did not differ significantly among the groups. The serum levels of the biomarkers varied at different time points. The serum levels of NGF on days 1 and 3, Wnt-3a on days 3 and 14, and ACTH on days 1, 3, and 7 were significantly higher in the bone fracture plus brain injury group than in the bone fracture group. Conclusions: Brain injury increases callus formation in simultaneous bone fracture. Considering the time point, early NGF, Wnt-3a, and ACTH elevation might be associated with early callus formation enhancement. The results indicate that these brain injury-induced biomarkers might play crucial role in accelerating bone healing.

  17. Induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    CSIR Research Space (South Africa)

    Ripamonti, U

    2008-01-01

    Full Text Available proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis...

  18. Runx2 expression is associated with pathologic new bone formation around radicular cysts: an immunohistochemical demonstration.

    Science.gov (United States)

    Kusafuka, Kimihide; Sasaguri, Kenichi; Sato, Sadao; Takemura, Tamiko; Kameya, Toru

    2006-09-01

    Radicular cysts are the most common cysts in human jaw bones. These lesions induce bone remodeling of the surrounding alveolar bones, which was termed 'condensing osteitis', and was suggested to be related to cells of the osteoblastic lineage. The Runx2 (core-binding protein [cbfa]1/polyoma enhancer-binding protein [pebp]2alphaA) was shown to be a DNA-binding transcriptional molecule expressed in osteoprogenitor cells. We confirmed the specificity of anti-Runx2 antiserum, using Western blotting analysis. We investigated the expression and localization of Runx2 in 32 radicular cyst cases with bone tissue fragments, immunohistochemically. Signals for Runx2 were seen in 18 cases (56.3%) of radicular cysts with bone formation. These signals were immunolocalized in the nuclei of the spindle-shaped osteoprogenitor cells in the cyst walls, whereas only a few signals were seen in the cuboidal osteoblastic cells near the fibrous bones. Signals for type I collagen were immunolocalized in the dense collagen fibers in the cyst walls and in the matrix of the fibrous bone around the radicular cysts, whereas no signals were seen on the inner portions with inflammatory cell infiltration of the cyst walls. Very weak signals for transforming growth factor (TGF)-beta1 were infrequently seen in the osteoblasts of the fibrous bone, whereas signals for TGF-beta2 were observed in young osteocytes in the fibrous bones, in B-cell lymphocytes infiltrating into the inner portions, and on the cellular membranes of the lining epithelium. The nuclear expression of Runx2 in spindle-shaped cells in the outer portions may play an essential role in the induction of fibrous bone tissue around radicular cysts. TGF-beta2 may play a role in the production of type I collagen, which acts as a template for pathologic new bone formation, in radicular cysts.

  19. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O' Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  20. Development of a Calcifiable Matrix for Bone Formation.

    Science.gov (United States)

    1987-09-01

    at 3.5 micrometers, and alternating sections were stained with Masson -Goldner trichrome and von Kossa stains. Histomorphometric analysis was...a modified Masson -Goldner trichrome and von Kossa stains. Histological specimens were assessed for local host responses. Inflammation and cellular...host bone (B), fibrous tissue (F). (Goldner trichrome , 16 x) 0+ Fig. 4b: 42 days, same field as 3a showing numerous calcification islands within

  1. Formation of hollow bone-like morphology of calcium carbonate on surfactant/polymer templates

    Science.gov (United States)

    Mantilaka, M. M. M. G. P. G.; Pitawala, H. M. T. G. A.; Rajapakse, R. M. G.; Karunaratne, D. G. G. P.; Upul Wijayantha, K. G.

    2014-04-01

    Novel hollow, bone-like structures of Precipitated Calcium Carbonate (PCC) are fabricated, for the first time, starting from naturally occurring dolomite. The hollow, bone-like structures are prepared by precipitating calcium carbonate on self-assembled poly(acrylic acid)/cetyltrimethylammonium chloride (PAA/CTAC) template. Fourier Transform Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and Field Emission Scanning Electron Microscopic (FE-SEM) studies reveal that the bone-like structure is composed of Amorphous Calcium Carbonate (ACC) nanoparticles in the center and calcite nanoparticles at the edges. Bone-like PCC particles are in particle length of 2-3 μm and particle width of 1 μm. The internal hollow structures of bone-like particles are observed from TEM images. As identified by FE-SEM images, the bone-like structure has been formed through the crystal growth of initially formed ACC nanoparticles. The ACC particles are stabilized in the center while the calcite crystals have been grown from the ACC toward the edges of the structure to form a bone-like morphology. We also propose a possible mechanism for the formation of hollow bone-like PCC in this study. The fabricated hollow, bone-like PCC has potential applications in the preparation of release systems such as drugs, cosmetics and pigments.

  2. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  3. Geochemical and mineralogical studies of dinosaur bone from the Morrison Formation at Dinosaur Ridge

    Science.gov (United States)

    Modreski, P.J.

    2001-01-01

    The dinosaur bones first discovered in 1877 in the Upper Jurassic Morrison Formation at Morrison, Colorado were the first major find of dinosaur skeletons in the western U.S. and led to the recognition of four new dinosaur genera (Apatosaurus, Allosaurus, Diplodocus, and Stegosaurus). Eight articles dealing with these bones which appeared as research reports in the annual reports of the Friends of Dinosaur Ridge from 1990-1999 are condensed and summarized with some additional comments. Two of the articles are about the mineralogy and preservation of the bones; two are about the physical description of the bone occurrence; two are about the history of the site, and two are about use of novel instrumental methods (ground-penetrating radar and a directional scintillometer) to search for new bones.

  4. Rapid-prototype endoprosthesis for palliative reconstruction of an upper extremity after resection of bone metastasis.

    Science.gov (United States)

    Pruksakorn, Dumnoensun; Chantarapanich, Nattapon; Arpornchayanon, Olarn; Leerapun, Taninit; Sitthiseripratip, Kriskrai; Vatanapatimakul, Natapoom

    2015-03-01

    To present a rapid-prototype (RP) endoprosthesis replacement after tumor resection in patients with bone metastasis of the upper extremity. The short-term complications and functional outcomes were evaluated as well as the survival of patients and endoprosthesis. Bone metastasis patients who required bone resection and endoprosthesis replacement were enrolled and consented before operation. Custom-made endoprosthesis was fabricated from polymethyl methacrylate assisted by RP technology. After surgery was performed, patients were followed up daily until discharge and monthly until 6 months postoperatively for immediate post-operative complications and for signs of endoprosthesis failure. The functional outcome was evaluated 6 months postoperatively by the Musculoskeletal Tumor Society score (MTSS) and the Mankin score. Thereafter, patients' survival and arm condition were monitored every 3 months. Sixteen cases participated on this study. There were nine proximal-, four total- and two distal humerus, and one proximal ulna replacement. The median follow-up period was 486 days. The mean MTSS was 55 % and the Mankin score was good in 64 % and fair in 36 % of the patients. Glenohumeral subluxation was observed in 23 % of the patients; however, a stable shoulder was achieved in all cases. There were no prosthesis failure or systemic breakage. An RP endoprosthesis may have significant advantages when the entire humerus needs to be replaced, or periarticular sites are involved. This technique offers custom-made endoprosthesis with enough durability, and in a relatively short production time at reasonable costs which are suitable for palliative reconstruction.

  5. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  6. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus.

    Science.gov (United States)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Green, Thomas A; Lotinun, Sutada; Kveiborg, Marie; Horne, William C; Nestler, Eric J; Baron, Roland

    2012-08-01

    The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention because of its potential relevance to osteoporosis, obesity, and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the regulation of both energy balance and bone homeostasis, little is known of the underlying mechanisms, including the possible involvement of transcriptional factors within the hypothalamus. Transgenic mice overexpressing ΔFosB, a splice variant of the AP-1 transcription factor FosB with mixed agonist-antagonistic properties, have increased energy expenditure and bone mass. Because these mice express ΔFosB in bone, fat, and hypothalamus, we sought to determine 1) whether overexpression of ΔFosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2) whether these effects were the result of antagonism to AP-1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ΔFosB to the ventral hypothalamus of wild-type mice induced a profound increase in both energy expenditure and bone formation and bone mass. This effect was phenocopied, at an even stronger level, by overexpression of a dominant-negative DNJunD, a pure AP-1 antagonist. Taken together, these results suggest that downregulation of AP-1 activity in the hypothalamus profoundly increases energy expenditure and bone formation, leading to both a decrease in adipose mass and an increase in bone mass. These findings may have physiological implications because ΔFosB is expressed and regulated in the hypothalamus. Copyright © 2012 American Society for Bone and Mineral Research.

  7. Hail formation triggers rapid ash aggregation in volcanic plumes.

    Science.gov (United States)

    Van Eaton, Alexa R; Mastin, Larry G; Herzog, Michael; Schwaiger, Hans F; Schneider, David J; Wallace, Kristi L; Clarke, Amanda B

    2015-08-03

    During explosive eruptions, airborne particles collide and stick together, accelerating the fallout of volcanic ash and climate-forcing aerosols. This aggregation process remains a major source of uncertainty both in ash dispersal forecasting and interpretation of eruptions from the geological record. Here we illuminate the mechanisms and timescales of particle aggregation from a well-characterized 'wet' eruption. The 2009 eruption of Redoubt Volcano, Alaska, incorporated water from the surface (in this case, a glacier), which is a common occurrence during explosive volcanism worldwide. Observations from C-band weather radar, fall deposits and numerical modelling demonstrate that hail-forming processes in the eruption plume triggered aggregation of ∼95% of the fine ash and stripped much of the erupted mass out of the atmosphere within 30 min. Based on these findings, we propose a mechanism of hail-like ash aggregation that contributes to the anomalously rapid fallout of fine ash and occurrence of concentrically layered aggregates in volcanic deposits.

  8. Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation

    DEFF Research Database (Denmark)

    Brum, A M; Leije, M; J, Schreuders-Koedam

    2017-01-01

    involved in osteoblast differentiation of human bone marrow–derived MSCs (hMSCs). We identified the gene chloride intracellular channel protein 3 (CLIC3) to be strongly upregulated during MSC-derived osteoblast differentiation. Lentiviral overexpression of CLIC3 in hMSCs caused a 60% increase of matrix......-fold increase in bone formation (0.33% versus 5.05% bone area relative to scaffold). Using a Clic3-His-tagged pull-down assay and liquid chromatography–mass spectrometry (LS/MS)-based proteomics analysis in lysates of osteogenically differentiated hMSCs, we showed that CLIC3 interacts with NIMA...

  9. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review.

    Science.gov (United States)

    Rathe, Florian; Junker, Rüdiger; Chesnutt, Betsy M; Jansen, John A

    2009-09-01

    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic review. Main results of the reviewed articles were (i) guide tissue regeneration (GTR) of infrabony defects seems to result in a higher degree of bone regeneration compared to treatment with EMD; (ii) combined therapy (GTR + EMD) of infrabony defects might not lead to better results than GTR therapy alone; (iii) there seems to be no additional benefit of combined therapy (GTR + EMD) in furcation defects over GTR therapy alone; (iv) EMD seems to lead to more bone regeneration of infrabony defects compared to open flap debridement; (v) however, EMD application might result in more bone formation when applied in supporting defects compared to nonsupporting defects; and (vi) EMD does not seem to promote external jaw/parietal bone formation in the titanium capsule model. The results of one study that suggest that EMD increases the initial growth of trabecular bone around endosseous implants by new bone induction need to be confirmed by additional research.

  10. Agrobacteria lacking ornithine lipids induce more rapid tumour formation

    Science.gov (United States)

    Vences-Guzmán, Miguel Ángel; Guan, Ziqiang; Bermúdez-Barrientos, José Roberto; Geiger, Otto; Sohlenkamp, Christian

    2013-01-01

    Summary Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread among Gram-negative bacteria. Their basic structure consists of a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of ornithine and a second fatty acyl group ester-linked to the 3-hydroxy position of the first fatty acid. It has been shown that OLs can be hydroxylated within the amide-linked fatty acyl moiety, the secondary fatty acyl moiety or within the ornithine moiety. These modifications have been related to increased stress tolerance and symbiotic proficiency in different organisms such as Rhizobium tropici or Burkholderia cenocepacia. Analysing the membrane lipid composition of the plant pathogen Agrobacterium tumefaciens we noticed that it forms two different OLs. In the present work we studied if OLs play a role in stress tolerance and pathogenicity in A. tumefaciens. Mutants deficient in the OLs biosynthesis genes olsB or olsE were constructed and characterized. They either completely lack OLs (ΔolsB) or only form the unmodified OL (ΔolsE). Here we present a characterization of both OL mutants under stress conditions and in a plant transformation assay using potato tuber discs. Surprisingly, the lack of agrobacterial OLs promotes earlier tumour formation on the plant host. PMID:22958119

  11. Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus

    Science.gov (United States)

    Haffner‐Luntzer, Melanie; Heilmann, Aline; Rapp, Anna Elise; Roessler, Robin; Schinke, Thorsten; Amling, Michael; Ignatius, Anita

    2016-01-01

    Background and Purpose Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing. Experimental Approach In the present study, we investigated the effects of a monoclonal anti‐Mdk antibody (Mdk‐Ab) on bone healing using a standardized femur osteotomy model in mice. Additional in vitro experiments using chondroprogenitor and preosteoblastic cells were conducted to analyse the effects of recombinant Mdk and Mdk‐Ab on differentiation markers and potential binding partners in these cells. Key Results We demonstrated that treatment with Mdk‐Ab accelerated bone healing in mice based on increased bone formation in the fracture callus. In vitro experiments using preosteoblastic cells showed that Mdk‐Ab treatment abolished the Mdk‐induced negative effects on the expression of osteogenic markers and Wnt/β‐catenin target proteins, whereas the differentiation of chondroprogenitor cells was unaffected. Phosphorylation analyses revealed an important role for the low‐density lipoproteinLDL receptor‐related protein 6 in Mdk signalling in osteoblasts. Conclusions and Implications We conclude that Mdk‐Ab treatment may be a potential novel therapeutic strategy to enhance fracture healing in patients with orthopaedic complications such as delayed healing or non‐union formation. PMID:27111560

  12. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent

    2011-01-01

    support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces...

  13. Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

    Science.gov (United States)

    2011-04-01

    distribution was determined by dynamic laser light scattering (Malvern ZetaSizer 3000HS), and the spherical particle morphology was confirmed by SEM.37 For...Talwar, R., Di Silvio, L., Hughes, F.J., and King, G.N. Effects of carrier release kinetics on bone morphogenetic protein-2- induced periodontal

  14. PPARG Post-translational Modifications Regulate Bone Formation and Bone Resorption

    Directory of Open Access Journals (Sweden)

    L.A. Stechschulte

    2016-08-01

    Full Text Available The peroxisome proliferator-activated receptor gamma (PPARγ regulates osteoblast and osteoclast differentiation, and is the molecular target of thiazolidinediones (TZDs, insulin sensitizers that enhance glucose utilization and adipocyte differentiation. However, clinical use of TZDs has been limited by side effects including a higher risk of fractures and bone loss. Here we demonstrate that the same post-translational modifications at S112 and S273, which influence PPARγ pro-adipocytic and insulin sensitizing activities, also determine PPARγ osteoblastic (pS112 and osteoclastic (pS273 activities. Treatment of either hyperglycemic or normoglycemic animals with SR10171, an inverse agonist that blocks pS273 but not pS112, increased trabecular and cortical bone while normalizing metabolic parameters. Additionally, SR10171 treatment modulated osteocyte, osteoblast, and osteoclast activities, and decreased marrow adiposity. These data demonstrate that regulation of bone mass and energy metabolism shares similar mechanisms suggesting that one pharmacologic agent could be developed to treat both diabetes and metabolic bone disease.

  15. Effect of a low-level laser on bone regeneration after rapid maxillary expansion.

    Science.gov (United States)

    Cepera, Fernanda; Torres, Fernando C; Scanavini, Marco A; Paranhos, Luiz R; Capelozza Filho, Leopoldino; Cardoso, Mauricio A; Siqueira, Danieli C R; Siqueira, Danilo F

    2012-04-01

    In this study, we evaluated the effects of a low-level laser on bone regeneration in rapid maxillary expansion procedures. Twenty-seven children, aged 8 to 12 years, took part in the experiment, with a mean age of 10.2 years, divided into 2 groups: the laser group (n = 14), in which rapid maxillary expansion was performed in conjunction with laser use, and the no-laser group (n = 13), with rapid maxillary expansion only. The activation protocol of the expansion screw was 1 full turn on the first day and a half turn daily until achieving overcorrection. The laser type used was a laser diode (TWIN Laser; MMOptics, São Carlos, Brazil), according to the following protocol: 780 nm wavelength, 40 mW power, and 10 J/cm(2) density at 10 points located around the midpalatal suture. The application stages were 1 (days 1-5 of activation), 2 (at screw locking, on 3 consecutive days), 3, 4, and 5 (7, 14, and 21 days after stage 2). Occlusal radiographs of the maxilla were taken with the aid of an aluminum scale ruler as a densitometry reference at different times: T1 (initial), T2 (day of locking), T3 (3-5 days after T2), T4 (30 days after T3), and T5 (60 days after T4). The radiographs were digitized and submitted to imaging software (Image Tool; UTHSCSA, San Antonio, Tex) to measure the optic density of the previously selected areas. To perform the statistical test, analysis of covariance was used, with the time for the evaluated stage as the covariable. In all tests, a significance level of 5% (P maxillary expansion, provided efficient opening of the midpalatal suture and influenced the bone regeneration process of the suture, accelerating healing. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  16. CLINICAL ASPECTS AND BIOCHEMICAL MARKERS OF BONE FORMATION AFTER LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    V.P. Buzulina

    2012-01-01

    Full Text Available Biochemical markers of bone formation [osteocalcin (OC, N-terminal propeptid of type 1 procollagen (P1NP, bone isoferment of alkaline phosphatase (BALP] were estimated in 34 recipients after liver transplantation. Three types of deviation have been demonstrated: combination elevated circulating levels OC and P1NP with normal levels BALP in recipients without clinical postoperative complication; combination lower levels OC and BALP with normal levels P1NP in recipients as a result of corticosteroid therapy prior/ following transplantation; superior levels P1NP with normal levels OC and BALP which results excessive accumulation hepatic collagen formation in recipients with postoperative clinical complication. 

  17. Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis

    Science.gov (United States)

    Marriott, Ian

    2013-01-01

    The mechanisms underlying the destruction of bone tissue in osteomyelitis are only now being elucidated. While some of the tissue damage associated with osteomyelitis likely results from the direct actions of bacteria and infiltrating leukocytes, perhaps exacerbated by bacterial manipulation of leukocyte survival pathways, infection-induced bone loss predominantly results from an uncoupling of the activities of osteoblasts and osteoclasts. Bacteria or their products can directly increase osteoclast formation and activity, and the inflammatory milieu at sites of infection can further promote bone resorption. In addition, osteoclast activity is critically regulated by osteoblasts that can respond to bacterial pathogens and foster both inflammation and osteoclastogenesis. Importantly, bone loss during osteomyelitis is also brought about by a decline in new bone deposition due to decreased bone matrix synthesis and by increased rates of osteoblast apoptosis. Extracellular bacterial components may be sufficient to reduce osteoblast viability, but the causative agents of osteomyelitis are also capable of inducing continuous apoptosis of these cells by activating intrinsic and extrinsic cell death pathways to further uncouple bone formation and resorption. Interestingly, bacterial internalization appears to be required for maximal osteoblast apoptosis, and cytosolic inflammasome activation may act in concert with autocrine/paracrine death receptor-ligand signaling to induce cell death. The manipulation of apoptotic pathways in infected bone cells could be an attractive new means to limit inflammatory damage in osteomyelitis. However, the mechanism that is the most important in bacterium-induced bone loss has not yet been identified. Furthermore, it remains to be determined whether the host would be best served by preventing osteoblast cell death or by promoting apoptosis in infected cells. PMID:24392356

  18. Energy Expenditure and Bone Formation Share a Common Sensitivity to AP-1 Transcription in the Hypothalamus

    Science.gov (United States)

    Rowe, Glenn C.; Vialou, Vincent; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Green, Thomas A.; Lotinun, Sutada; Kveiborg, Marie; Horne, William C.; Nestler, Eric J.; Baron, Roland

    2012-01-01

    The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention due to its potential relevance to osteoporosis, obesity and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the regulation of both energy balance and bone homeostasis, little is known of the underlying mechanisms, including the possible involvement of transcriptional factors within the hypothalamus. Transgenic mice overexpressing ΔFosB, a splice variant of the AP1 transcription factor FosB with mixed agonist-antagonistic properties, have increased energy expenditure and bone mass. Since these mice express ΔFosB in bone, fat and hypothalamus, we sought to determine 1) whether overexpression of ΔFosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ΔFosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass. This effect was phenocopied, at an even stronger level, by overexpressiong of a dominant-negative DNJunD, a pure AP1 antagonist. Taken together these results suggest that downregulation of AP1 activity in the hypothalamus profoundly increases energy expenditure and bone formation, leading to both a decrease in adipose mass and an increase in bone mass. These findings may have physiological implications since ΔFosB is expressed and regulated in the hypothalamus. PMID:22461201

  19. Nanosized Hydroxyapatite Coating on PEEK Implants Enhances Early Bone Formation: A Histological and Three-Dimensional Investigation in Rabbit Bone

    Directory of Open Access Journals (Sweden)

    Pär Johansson

    2015-06-01

    Full Text Available Polyether ether ketone (PEEK has been frequently used in spinal surgery with good clinical results. The material has a low elastic modulus and is radiolucent. However, in oral implantology PEEK has displayed inferior ability to osseointegrate compared to titanium materials. One idea to reinforce PEEK would be to coat it with hydroxyapatite (HA, a ceramic material of good biocompatibility. In the present study we analyzed HA-coated PEEK tibial implants via histology and radiography when following up at 3 and 12 weeks. Of the 48 implants, 24 were HA-coated PEEK screws (test and another 24 implants served as uncoated PEEK controls. HA-coated PEEK implants were always osseointegrated. The total bone area (BA was higher for test compared to control implants at 3 (p < 0.05 and 12 weeks (p < 0.05. Mean bone implant contact (BIC percentage was significantly higher (p = 0.024 for the test compared to control implants at 3 weeks and higher without statistical significance at 12 weeks. The effect of HA-coating was concluded to be significant with respect to early bone formation, and HA-coated PEEK implants may represent a good material to serve as bone anchored clinical devices.

  20. Three dimensional evaluation of alveolar bone changes in response to different rapid palatal expansion activation rates

    Directory of Open Access Journals (Sweden)

    Brian LaBlonde

    Full Text Available ABSTRACT Introduction: The aim of this multi-center retrospective study was to quantify the changes in alveolar bone height and thickness after using two different rapid palatal expansion (RPE activation protocols, and to determine whether a more rapid rate of expansion is likely to cause more adverse effects, such as alveolar tipping, dental tipping, fenestration and dehiscence of anchorage teeth. Methods: The sample consisted of pre- and post-expansion records from 40 subjects (age 8-15 years who underwent RPE using a 4-banded Hyrax appliance as part of their orthodontic treatment to correct posterior buccal crossbites. Subjects were divided into two groups according to their RPE activation rates (0.5 mm/day and 0.8 mm/day; n = 20 each group. Three-dimensional images for all included subjects were evaluated using Dolphin Imaging Software 11.7 Premium. Maxillary base width, buccal and palatal cortical bone thickness, alveolar bone height, and root angulation and length were measured. Significance of the changes in the measurements was evaluated using Wilcoxon signed-rank test and comparisons between groups were done using ANOVA. Significance was defined at p ≤ 0.05. Results: RPE activation rates of 0.5 mm per day (Group 1 and 0.8 mm per day (Group 2 caused significant increase in arch width following treatment; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Buccal alveolar height and width decreased significantly in both groups. Both treatment protocols resulted in significant increases in buccal-lingual angulation of teeth; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Conclusion: Both activation rates are associated with significant increase in intra-arch widths. However, 0.8 mm/day resulted in greater increases. The 0.8 mm/day activation rate also resulted in more increased dental tipping and decreased buccal alveolar bone thickness over 0.5 mm/day.

  1. Osteogenic protein 1 device increases bone formation and bone graft resorption around cementless implants

    DEFF Research Database (Denmark)

    Jensen, Thomas B; Overgaard, Søren; Lind, Martin

    2002-01-01

    In each femoral condyle of 8 Labrador dogs, a non weight-bearing hydroxyapatite-coated implant was inserted surrounded by a 3 mm gap. Each gap was filled with bone allograft or ProOsteon with or without OP-1 delivered in a bovine collagen type I carrier (OP-1 device). 300 microg OP-1 was used...... in the 0.75 cc gap surrounding the implant. After 3 weeks, the OP-1 device enhanced implant fixation by 800% (p...

  2. Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Tegan L Cheng

    2015-10-01

    Full Text Available Sucrose acetate isobutyrate (SAIB is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2 and found synergy when co-delivering zoledronic acid (ZA and hydroxyapatite (HA nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP nor Bioglass (BG 45S5 had a significant effect on bone volume (BV alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%, and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%. These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering.

  3. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial

    DEFF Research Database (Denmark)

    Raina, D. B.; Gupta, A.; Petersen, M. M.

    2016-01-01

    Objectives: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth...... as an osteoinductive niche, and provides the required cells for bone formation....

  4. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

    DEFF Research Database (Denmark)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa

    2012-01-01

    The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention due to its potential relevance to osteoporosis, obesity and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the re......The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention due to its potential relevance to osteoporosis, obesity and diabetes. Although central effectors within the hypothalamus have been shown to contribute......) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  5. Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures.

    Science.gov (United States)

    Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Simonet, Jacqueline; Stanley, Alexandra; Albertson, Craig; Fisher, Shannon

    2016-05-15

    During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Acute changes in biochemical markers of bone resorption and formation after Thai traditional massage.

    Science.gov (United States)

    Saetung, Sunee; Chailurkit, La-or; Ongphiphadhanakul, Boonsong

    2010-07-01

    Mechanical loadings by active exercise or passive low amplitude vibration have been demonstrated to enhance bone mass or delay bone loss. Traditional Thai massage can be anabolic to bone due to the application of physical loading on the body in a rhythmic fashion. To explore the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover immediately after the massage. Subjects consisted of 30 healthy females aged 20-40 years. Each subject received Thai traditional massage for 2 hours by a single masseuse. Bone mineral density (BMD) at baseline was measured by dual-energy X-ray absorptiometry (DEXA). C-terminal telopeptide of type 1 collagen (CTx-I) and total procollagen type 1 amino-terminal propeptide (P1NP) were determined by electrochemiluminescence immunoassay. There was a 4.8% increase in serum P1NP concentrations after massage (median 43.4 ng/ml vs. 41.3 ng/ml, p massage (median 2-hour vs. baseline 0.29 ng/ml vs. 0.31 ng/ml, p traditional massage induces acute changes in bone formation and resorption markers. Study on the more prolonged effects of Thai traditional massage is warranted to explore its implication in the enhancement of bone health.

  7. Locally Applied Simvastatin Promotes Bone Formation in a Rat Model of Spinal Fusion.

    Science.gov (United States)

    Ishihara, Toshinobu; Miyazaki, Masashi; Notani, Naoki; Kanezaki, Shozo; Kawano, Masanori; Tsumura, Hiroshi

    2017-09-01

    Simvastatin, an inexpensive lipid-lowering drug widely used to prevent cardiovascular disorders, is known to increase osteoblastic activity, inhibit osteoclastic activity, and stimulate osteoblastic production of bone morphogenetic protein 2. Furthermore, local simvastatin application increased bone formation in animal models of fracture or bone defects. We investigated the effect of locally applied simvastatin in a rat model of spinal fusion. We performed posterolateral lumbar fusion surgery with iliac crest autograft in 36 rats divided into group I (n = 17; implanted with a gelatin scaffold) and group II (n = 19; implanted with a gelatin scaffold infused with 0.5 mg simvastatin). The rats were euthanized at 6 or 12 weeks postoperatively, and the spines were explanted and assessed. The fusion rates in group II (16.7%: 6 weeks, 30%: 12 weeks) were considerably higher than those in groups I (0%: 6 weeks, 0%: 12 weeks). The 6- and 12-week radiographic scores were significantly higher in group II than in group I. High-resolution micro-computerized tomography revealed that the tissue and bone volumes of the callus tended to be higher in group II than in group I. Histologic analysis of the spines explanted after 12 weeks demonstrated new bone formation between the transverse processes in group II, but thicker and wider individual trabeculae with fibrotic tissue and muscle fiber between the transverse processes in group I. Locally applied simvastatin was efficacious in accelerating bone formation in our rat model of spinal fusion, supporting its potential clinical application as a promoter of bone morphogenesis in spinal fusion. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1942-1948, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. The application of rapid prototyping to improve bone reconstruction in immediate dentoalveolar restoration: a case report.

    Science.gov (United States)

    Martins da Rosa, José Carlos; Fadanelli, Marcos Alexandre; Zimmerman, Diego; de Oliveira Rosa, Ariádene Cristina Pértile

    This article describes the use of rapid prototyping (RP) for diagnosis, planning, and execution of the reconstruction of hard and soft tissue in socket defects using immediate dentoalveolar restoration (IDR). In cases of tissue loss in anterior dental areas, esthetic rehabilitation poses a major challenge with respect to treatment planning with the goal of long-term tissue maintenance. The IDR technique consists of immediate reconstruction in a single procedure of bone and soft tissue around implants placed immediately after extraction, and prosthetic rehabilitation. As this procedure is immediate and flapless, the correct diagnosis of tissue loss and correct graft adaptation are mandatory. RP can increase the precision of the procedure, as demonstrated using a clinical case characterized by total loss of the buccal bone wall and gingival recession. The results were evaluated by clinical assessment, photography, radiography, cone beam computed tomography (CBCT), and prototyping. The application of RP facilitated the execution of IDR as it enabled more accurate diagnosis of the socket defect and more precise adaptation of the tissue graft. A clinical study should be conducted to evaluate the effects of RP on the clinical results of the IDR technique.

  9. Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Shi, Kaikai; Frary, Charles Edward

    2015-01-01

    expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize...

  10. Influence of fluoride in poly(d,l-lactide)/apatite composites on bone formation.

    Science.gov (United States)

    Luo, X; Barbieri, D; Passanisi, G; Yuan, H; de Bruijn, J D

    2015-05-01

    The influence of fluoride in poly(d,l-lactide)/apatite composites on ectopic bone formation was evaluated in sheep. Nano-apatite powders with different replacement levels of OH groups by fluoride (F) (0% (F0), 50% (F50), 100% (F100), and excessive (F200)) were co-extruded with poly (d,l-lactide) at a weight ratio of 1:1. Fluoride release from the composites (CF0, CF50, CF100, and CF200) was evaluated in vitro and bone formation was assessed after intramuscular implantation in sheep. After 24 weeks in simulated physiological solution, CF0 and CF50 showed negligible fluoride release, whereas it was considerable from the CF100 and CF200 composites. Histology showed that the incidence of de novo bone formation decreased in implants with increasing fluoride content indicating a negative influence of fluoride on ectopic bone formation. Furthermore, a significant decrease in resorption of the high fluoride-content composites and a reduction in the number of multinucleated giant cells were seen. These results show that instead of promoting, the presence of fluoride in poly(d,l-lactide)/apatite composites seemed to suppresses their resorption and osteoinductive potential in non-osseous sites. © 2014 Wiley Periodicals, Inc.

  11. Sintered porous hydroxyapatites with intrinsic osteoinductive activity: geometric induction of bone formation

    CSIR Research Space (South Africa)

    Ripamonti, U

    1999-08-01

    Full Text Available of bone formation. Monolithic discs of sintered hydroxyapatite, fabricated with concavities of 800 and 1600 mu m diameter on both planar surfaces, were implanted in the rectus abdominis of the baboon (Papio ursinus). Histology on days 30 and 90 revealed de...

  12. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    level laser therapy (LLLT) on osteoblastic bone formation and relapse during expansion of rat palatal sutures. Materials and Methods: Thirty‑two Wistar rats were randomly allocated into two groups of 16 rats each. In the first group, LLLT was ...

  13. Size matters: effects of PLGA-microsphere size in injectable CPC/PLGA on bone formation

    NARCIS (Netherlands)

    Liao, H.; Lanao, R.P.; Beucken, J.J.J.P van den; Zhou, N.; Both, S.K.; Wolke, J.G.C.; Jansen, J.A.

    2016-01-01

    The aim of this study was to evaluate the effect of PLGA microsphere dimensions on bone formation after injection of calcium phosphate cement (CPC)/PLGA in a guinea pig tibial intramedullarly model. To this end, injectable CPC/PLGA formulations were prepared using PLGA microspheres with either a

  14. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    2015-01-12

    Jan 12, 2015 ... the osseous palate facing the oral cavity. This procedure was used because bone formation in surface regions was sometimes irregular, and quantitative measurements were not possible. Histological and the histomorphometric assessment. Two examiners blinded to the sources of sections performed.

  15. Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements

    NARCIS (Netherlands)

    van de Belt, H; Neut, D; Schenk, W; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos. and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials

  16. Relating cell proliferation to in vivo bone formation in porous Ca/P scaffolds

    NARCIS (Netherlands)

    van Gaalen, S.M.; de Bruijn, J.D.; Wilson, C.E.; van Blitterswijk, C.A.; Verbout, A.J.; Alblas, J.; Dhert, W.J.A.|info:eu-repo/dai/nl/10261847X

    2010-01-01

    Relating cell proliferation to in vivo bone formation in porous Ca/P scaffolds Steven M. van Gaalen1,*, Joost D. de Bruijn2, Clayton E. Wilson3, Clemens A. van Blitterswijk3, Abraham J. Verbout1, Jacqueline Alblas1, Wouter J. A. Dhert1,4Article first published online: 2 FEB 2009 Abstract Most

  17. Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading.

    Directory of Open Access Journals (Sweden)

    Sara Temiyasathit

    Full Text Available Primary cilia, solitary microtubule-based structures that grow from the centriole and extend into the extracellular space, have increasingly been implicated as sensors of a variety of biochemical and biophysical signals. Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation. We propose that primary cilia are also important in mechanically regulated bone formation in adults and that their malfunction could play a role in complex multi-factorial bone diseases, such as osteoporosis. In this study, we generated mice with an osteoblast- and osteocyte-specific knockout of Kif3a, a subunit of the kinesin II intraflagellar transport (IFT protein; IFT is required for primary cilia formation, maintenance, and function. These Colα1(I 2.3-Cre;Kif3a(fl/fl mice exhibited no obvious morphological skeletal abnormalities. Skeletally mature Colα1(I 2.3-Cre;Kif3a(fl/fl and control mice were exposed to 3 consecutive days of cyclic axial ulna loading, which resulted in a significant increase in bone formation in both the conditional knockouts and controls. However, Colα1(I 2.3-Cre;Kif3a(fl/fl mice did exhibit decreased formation of new bone in response to mechanical ulnar loading compared to control mice. These results suggest that primary cilia act as cellular mechanosensors in bone and that their function may be critical for the regulation of bone physiology due to mechanical loading in adults.

  18. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Andreasen, Christina Møller; Dencker, Mads L.

    2015-01-01

    formation in concentric gap, and its enhancements on bone formation and implant fixation were at least as good as allograft. It is suggested that ABM/P-15 might be a good alternative biomaterial for bone implant fixation in this well-validated critical-size defect gap model in sheep. Nevertheless, future...

  19. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing.

    Science.gov (United States)

    Kazmers, Nikolas H; McKenzie, Jennifer A; Shen, Tony S; Long, Fanxin; Silva, Matthew J

    2015-12-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3 days (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1 day and 3 days in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1 day, but decreased Shh expression by 37% at 3 days. GDC-0449 decreased woven bone volume (-37%) and mineral density (-17%) at 7 days. Dynamic histomorphometry revealed that the 7 day callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3 days), osteoblastic differentiation (Osx expression at 1 day and 3 days), chondrogenic gene expression (Acan, Sox9, and Col2α1 expression at 1 day and 3 days), or bone resorption metrics (callus TRAP staining at 3 days, Rankl and Opg expression at 1 day and 3 days). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3 days, which was associated with increased Hif1α gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent

  20. Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro.

    Science.gov (United States)

    Blair, Harry C; Larrouture, Quitterie C; Li, Yanan; Lin, Hang; Beer-Stoltz, Donna; Liu, Li; Tuan, Rocky S; Robinson, Lisa J; Schlesinger, Paul H; Nelson, Deborah J

    2017-06-01

    We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and

  1. Feasibility of Using a Bone-Targeted, Macromolecular Delivery System Coupled with Prostaglandin E1 to Promote Bone Formation in Aged, Estrogen-Deficient Rats

    Science.gov (United States)

    Miller, S. C.; Pan, H.; Wang, D.; Bowman, B. M.; Kopečková, P.; Kopeček, J.

    2009-01-01

    Purpose Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer–Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods The uptake of FITC-labeled HPMA copolymer–Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions HPMA copolymers can be targeted to bone surfaces using Asp8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases. PMID:18758923

  2. [Influence of high molecular weight polyethylene on viability of osteoblasts and new bone formation].

    Science.gov (United States)

    Ren, Gaohong; Lin, Angru; Pei, Guoxian; Hu, Basheng

    2006-02-01

    To investigate the influence of high molecular weight polyethylene (HMWP) on the viability of osteoblasts and new bone formation in the process of fracture healing, the osteoblasts derived from adult human bone marrow were cultured in HMWP maceration extract and normal culture medium. The viability of the osteoblasts was measured by MTT assay, and the function of the osteoblasts was detected by use of alkaline phosphatase test kit. The locked double-plating (steel plate and HMWP plate) was implanted and fixed at the artificial fracture of distal femur of dogs. Specimens were gained at 3, 6, 9 and 12 weeks postoperatively, examined with macroscopy, microscope and scanning electron microscope (SEM). The results showed that HMWP did no harm to osteoblasts. There is no significant difference in activities of proliferation and alkaline phosphatase between HMWP maceration extract and normal culture medium at each observation time of at 2,4,8, and 14 dyas (P>0. 05). Bone tissue under the implanted HMWP plate manifested no absorption; the new bones formed under the HMWP plate and gradually matured as time went on. It is demonstrated in this study that HMWP has no adverse influence on the viability of osteoblasts and new bone formation and it can be used as internal fixation implant in treating fractures.

  3. The Effect of an Enamel Matrix Derivative (Emdogain Combined with Bone Ceramic on Bone Formation in Mandibular Defects: A Histomorphometric and Immunohistochemical Study in the Canine

    Directory of Open Access Journals (Sweden)

    Reza Birang

    2012-01-01

    Full Text Available Background. The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD and an osteoconductive bone ceramic (BC in improving bone regeneration. Materials and Methods. Four cylindrical cavities (6×6mm were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments—filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated—and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Results. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. Conclusion. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.

  4. The effect of an enamel matrix derivative (Emdogain) combined with bone ceramic on bone formation in mandibular defects: a histomorphometric and immunohistochemical study in the canine.

    Science.gov (United States)

    Birang, Reza; Abouei, Mohammad Shah; Razavi, Sayed Mohammad; Zia, Peyaman; Soolari, Ahmad

    2012-01-01

    The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD) and an osteoconductive bone ceramic (BC) in improving bone regeneration. Four cylindrical cavities (6 × 6 mm) were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments-filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated)-and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.

  5. The effect of heparan sulfate application on bone formation during distraction osteogenesis.

    Directory of Open Access Journals (Sweden)

    Marie Gdalevitch

    Full Text Available Bone morphogenetic proteins (BMPs are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS. The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone regenerate site in a mouse model of distraction osteogenesis (DO can accelerate bone healing and affect the expression of key members of the BMP signaling pathway. DO was performed on the right tibia of 115 adult male wild-type mice. At mid-distraction (day 11, half the group was injected locally with 5 µg of HS, while the other half was injected with saline. The mice were sacrificed at 2 time-points: mid-consolidation (34 days and full consolidation (51 days. The distracted tibial zone was then collected for analysis by μCT, radiology, biomechanical testing, immunohistochemistry, and histology. While μCT data showed no statistically significant difference in bone formation, the results of biomechanical testing in stiffness and ultimate force were significantly lower in the HS-injected bones at 51 days, compared to controls. Immunohistochemistry results also suggested a decrease in expression of several key members of the BMP signaling pathway at 34 days. Furthermore, wound dehiscence and infection rates were significantly elevated in the HS group compared to the controls, which resulted in a higher rate of euthanasia in the treatment group. Our findings demonstrate that exogenous application of 5 µg of HS in the distracted gap of a murine model had a negative impact on bone and wound healing.

  6. Radiographic evaluation and unusual bone formations in different genetic patterns in synpolydactyly

    Energy Technology Data Exchange (ETDEWEB)

    Yucel, Aylin; Acar, Murat [Afyon Kocatepe University School of Medicine, Department of Radiology, Afyon (Turkey); Kuru, Ilhami; Bozan, M. Eray [Afyon Kocatepe University School of Medicine, Department of Orthopaedics, Afyon (Turkey); Solak, Mustafa [Afyon Kocatepe University School of Medicine, Department of Genetics, Afyon (Turkey)

    2005-08-01

    To compare the radiological findings of heterozygous and homozygous subjects with synpolydactyly (SPD) and to discuss their unusual bone formations. Families with hand and foot SPD were examined. Genetic analysis was performed with blood samples and the pedigree was constructed. The affected individuals, especially those with distinctive phenotypic features, were invited to our orthopaedics clinic for further diagnostic studies. All participants underwent detailed clinical and X-ray examinations. Of the invited patients, 16 (five female and 11 male; age range 4-37 years, mean age 10.75 years) were included in our study, and hand and foot radiographs were obtained. All subjects had bilateral hand radiographs (32 hands), and 14 had bilateral foot radiographs (28 feet). Genetic analysis revealed 12 heterozygote (75%) and four (25%) homozygote phenotypes. Among patients enrolled into the study nine (three homozygotes, six heterozygotes) had SPD of both hands and feet bilaterally (tetrasynpolydactyly). Six unusual bone formations were observed in the hands and feet: delta phalanx, delta metacarpal/metatarsal, kissing delta phalanx, true double epiphysis, pseudoepiphysis and cone-shaped epiphysis. There were major differences in radiological and clinical manifestations of homozygote and heterozygote phenotypes. The homozygous SPD presented with very distinctive unusual bone formations. The existence and variety of unusual bones may indicate the severity of penetrance and expressivity of SPD. (orig.)

  7. A Rare Colon Cancer with Ossification: Pathogenetic Analysis of Bone Formation.

    Science.gov (United States)

    Noh, Byeong-Joo; Kim, Youn Wha; Park, Yong-Koo

    2016-07-01

    Heterotopic ossification occurring in colon cancer is an exceedingly rare event. The pathogenetic mechanism of tumor-related heterotopic bone formation remains unclear. Herein, we describe a rare case of colon cancer with ossification in a 76-year-old woman. We also highlight the etiology of heterotopic ossification by immunohistochemical evaluation of novel markers such as bone morphogenetic protein 9 (BMP9), osteocalcin, osteopontin, and β-catenin. BMP9 is one of the most potent osteogenetic BMPs. However, no previous research has been performed concerning BMP9 in heterotopic ossification arising in colon cancer. Subsequently, we suggest a hypothesis of tumor-associated heterotopic bone formation through this case. When osteoblastic indicators including BMP9, osteocalcin, and osteopontin are upregulated in tumor cells, osteoblast-like transformation of such tumor cells occurs. These tumor cells augment the release of interactive osteogenetic factors (BMP9, osteocalcin, and osteopontin) and stimulate uncommitted mesenchymal stromal cells into specific osteoblastic differentiation, contributing to heterotopic bone formation. This transformation of tumor cells is considered a type of epithelial-mesenchymal transition (EMT) because of overexpression of BMP9 and β-catenin. Patients should be followed closely because EMT has a tendency toward local recurrence. Our findings provide insight into the pathogenetic etiology of heterotopic ossification in colon cancer. © 2016 by the Association of Clinical Scientists, Inc.

  8. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.

    Science.gov (United States)

    Maes, Christa; Carmeliet, Peter; Moermans, Karen; Stockmans, Ingrid; Smets, Nico; Collen, Désiré; Bouillon, Roger; Carmeliet, Geert

    2002-02-01

    Vascular endothelial growth factor (VEGF)-mediated angiogenesis is an important part of bone formation. To clarify the role of VEGF isoforms in endochondral bone formation, we examined long bone development in mice expressing exclusively the VEGF120 isoform (VEGF120/120 mice). Neonatal VEGF120/120 long bones showed a completely disturbed vascular pattern, concomitant with a 35% decrease in trabecular bone volume, reduced bone growth and a 34% enlargement of the hypertrophic chondrocyte zone of the growth plate. Surprisingly, embryonic hindlimbs at a stage preceding capillary invasion exhibited a delay in bone collar formation and hypertrophic cartilage calcification. Expression levels of marker genes of osteoblast and hypertrophic chondrocyte differentiation were significantly decreased in VEGF120/120 bones. Furthermore, inhibition of all VEGF isoforms in cultures of embryonic cartilaginous metatarsals, through the administration of a soluble receptor chimeric protein (mFlt-1/Fc), retarded the onset and progression of ossification, suggesting that osteoblast and/or hypertrophic chondrocyte development were impaired. The initial invasion by osteoclasts and endothelial cells into VEGF120/120 bones was retarded, associated with decreased expression of matrix metalloproteinase-9. Our findings indicate that expression of VEGF164 and/or VEGF188 is important for normal endochondral bone development, not only to mediate bone vascularization but also to allow normal differentiation of hypertrophic chondrocytes, osteoblasts, endothelial cells and osteoclasts.

  9. Rapid Maxillary Expansion After Alveolar Bone Grafting With rhBMP-2 in UCLP Evaluated by Means of CBCT

    NARCIS (Netherlands)

    Garib, D.; Miranda, F.; Sathler, R.; Kuijpers-Jagtman, A.M.; Aiello, C.A.

    2017-01-01

    OBJECTIVE: To demonstrate the feasibility of rapid maxillary expansion (RME) after alveolar bone grafting (ABG) in complete unilateral cleft lip, alveolus and palate (UCLP) without damage to the grafted area. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies (HRAC), University of Sao

  10. A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva

    2015-01-01

    BACKGROUND: Understanding the regulation of mineral homeostasis and function of the skeleton as buffer for Calcium and Phosphate has regained new interest with introduction of the syndrome "Chronic Kidney Disease-Mineral and Bone Disorder"(CKD-MBD). The very rapid minute-to-minute regulation of p...

  11. Rapid prototyping for tissue-engineered bone scaffold by 3D printing and biocompatibility study.

    Science.gov (United States)

    He, Hui-Yu; Zhang, Jia-Yu; Mi, Xue; Hu, Yang; Gu, Xiao-Yu

    2015-01-01

    The prototyping of tissue-engineered bone scaffold (calcined goat spongy bone-biphasic ceramic composite/PVA gel) by 3D printing was performed, and the biocompatibility of the fabricated bone scaffold was studied. Pre-designed STL file was imported into the GXYZ303010-XYLE 3D printing system, and the tissue-engineered bone scaffold was fabricated by 3D printing using gel extrusion. Rabbit bone marrow stromal cells (BMSCs) were cultured in vitro and then inoculated to the sterilized bone scaffold obtained by 3D printing. The growth of rabbit BMSCs on the bone scaffold was observed under the scanning electron microscope (SEM). The effect of the tissue-engineered bone scaffold on the proliferation and differentiation of rabbit BMSCs using MTT assay. Universal testing machine was adopted to test the tensile strength of the bone scaffold. The leachate of the bone scaffold was prepared and injected into the New Zealand rabbits. Cytotoxicity test, acute toxicity test, pyrogenic test and intracutaneous stimulation test were performed to assess the biocompatibility of the bone scaffold. Bone scaffold manufactured by 3D printing had uniform pore size with the porosity of about 68.3%. The pores were well interconnected, and the bone scaffold showed excellent mechanical property. Rabbit BMSCs grew and proliferated on the surface of the bone scaffold after adherence. MTT assay indicated that the proliferation and differentiation of rabbit BMSCs on the bone scaffold did not differ significantly from that of the cells in the control. In vivo experiments proved that the bone scaffold fabricated by 3D printing had no acute toxicity, pyrogenic reaction or stimulation. Bone scaffold manufactured by 3D printing allows the rabbit BMSCs to adhere, grow and proliferate and exhibits excellent biomechanical property and high biocompatibility. 3D printing has a good application prospect in the prototyping of tissue-engineered bone scaffold.

  12. Immediate periodontal bone plate changes induced by rapid maxillary expansion in the early mixed dentition: CT findings

    Directory of Open Access Journals (Sweden)

    Daniela Gamba Garib

    2014-06-01

    Full Text Available OBJECTIVE: This study aimed at evaluating buccal and lingual bone plate changes caused by rapid maxillary expansion (RME in the mixed dentition by means of computed tomography (CT. METHODS: The sample comprised spiral CT exams taken from 22 mixed dentition patients from 6 to 9 years of age (mean age of 8.1 years presenting constricted maxillary arch treated with Haas-type expanders. Patients were submitted to spiral CT scan before expansion and after the screw activation period with a 30-day interval between T1 and T2. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal bone crest level of maxillary posterior deciduous and permanent teeth. Changes induced by expansion were evaluated using paired t test (p < 0.05. RESULTS: Thickness of buccal and lingual bone plates of posterior teeth remained unchanged during the expansion period, except for deciduous second molars which showed a slight reduction in bone thickness at the distal region of its buccal aspect. Buccal bone dehiscences were not observed in the supporting teeth after expansion. CONCLUSION: RME performed in mixed dentition did not produce immediate undesirable effects on periodontal bone tissues.

  13. Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading

    Science.gov (United States)

    Kubota, Takuo; Elalieh, Hashem Z.; Saless, Neema; Fong, Chak; Wang, Yongmei; Babey, Muriel; Cheng, Zhiqiang; Bikle, Daniel D.

    2013-11-01

    Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor-1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/-) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.

  14. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Hauge, Ellen M; Rolighed, Lars

    2014-01-01

    Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushing's syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events...

  15. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R

    2014-01-01

    limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, P...Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind......BMD, -13%, Pmuscle mass (-69%, Pmuscle cell cross sectional area (CSA) (-73%, P

  16. Effects of soccer vs swim training on bone formation in sedentary middle-aged women

    DEFF Research Database (Denmark)

    Mohr, Magni; Helge, Eva Wulff; Petersen, Liljan F

    2015-01-01

    .1 kg, body fat: 42.6 ± 5.7 %, systolic blood pressure/diastolic blood pressure: 138 ± 6/85 ± 3 mmHg] were randomized into soccer training (SOC, n = 21), high-intensity intermittent swimming (HS, n = 21), moderate-intensity swimming (MS, n = 21) intervention groups, and a control group (C, n = 20...... turnover markers, with concomitant increases in leg bone mass. No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training. Thus, soccer training appears to provide a powerful osteogenic stimulus in middle-aged women.......PURPOSE: The present study examined the effects of 15 weeks of soccer training and two different swimming training protocols on bone turnover in sedentary middle-aged women. METHODS: Eighty-three premenopausal mildly hypertensive women [age: 45 ± 6 (±SD) years, height: 165 ± 6 cm, weight: 80.0 ± 14...

  17. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren

    2015-01-01

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss...... in the mononuclear reversal cells colonising the surfaces. In conclusion, glucocorticoid treatment of ovariectomised sheep induced a significant bone loss, caused by an arrest of the reversal phase, resulting in an uncoupling of the bone formation and resorption during the reversal phase, as recently demonstrated....... Twenty female sheep were assigned for two groups; an untreated control group and an ovariectomised group treated with glucocorticoids (0.6mg/kg/day, 5 times weekly) for 7months. At 7months the glucocorticoid-treated ovariectomised sheep showed a significant change in the bone microstructure revealed...

  18. Cherubism gene Sh3bp2 is important for optimal bone formation, osteoblast differentiation, and function.

    Science.gov (United States)

    Mukherjee, Padma M; Wang, Chiachien J; Chen, I-Ping; Jafarov, Toghrul; Olsen, Bjorn R; Ueki, Yasuyoshi; Reichenberger, Ernst J

    2010-08-01

    Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and the mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described. We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation, and osteoblast function. We observed delays in early postnatal development of homozygous Sh3bp2(KI/KI) mice, which exhibited increased growth plate thickness and significantly decreased trabecular bone thickness and bone mineral density. Histomorphometric and microcomputed tomography analyses showed bone loss in the cranial and appendicular skeletons. Sh3bp2(KI/KI) mice also exhibited a significant decrease in osteoid formation that indicated a defect in osteoblast function. Calvarial osteoblast cell cultures had decreased alkaline phosphatase expression and mineralization, suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers such as collagen type I, alkaline phosphatase, and osteocalcin were decreased in osteoblast cultures from Sh3bp2(KI/KI) mice. These data suggest that Sh3bp2 regulates bone homeostasis through not only osteoclast-specific effects, but also through effects on osteoblast differentiation and function. Copyright (c) 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  19. Twist1- and Twist2-haploinsufficiency results in reduced bone formation.

    Directory of Open Access Journals (Sweden)

    Yanyu Huang

    Full Text Available Twist1 and Twist2 are highly homologous bHLH transcription factors that exhibit extensive highly overlapping expression profiles during development. While both proteins have been shown to inhibit osteogenesis, only Twist1 haploinsufficiency is associated with the premature synostosis of cranial sutures in mice and humans. On the other hand, biallelic Twist2 deficiency causes only a focal facial dermal dysplasia syndrome or additional cachexia and perinatal lethality in certain mouse strains. It is unclear how these proteins cooperate to synergistically regulate bone formation.Twist1 floxed mice (Twist1(f/f were bred with Twist2-Cre knock-in mice (Twist2(Cre/+ to generate Twist1 and Twist2 haploinsufficient mice (Twist1(f/+; Twist2(Cre/+. X-radiography, micro-CT scans, alcian blue/alizarin red staining, trap staining, BrdU labeling, immunohistochemistry, in situ hybridizations, real-time PCR and dual luciferase assay were employed to investigate the overall skeletal defects and the bone-associated molecular and cellular changes of Twist1(f/+;Twist2(Cre/+ mice.Twist1 and Twist2 haploinsufficient mice did not present with premature ossification and craniosynostosis; instead they displayed reduced bone formation, impaired proliferation and differentiation of osteoprogenitors. These mice exhibited decreased expressions of Fgf2 and Fgfr1-4 in bone, resulting in a down-regulation of FGF signaling. Furthermore, in vitro studies indicated that both Twist1 and Twist2 stimulated 4.9 kb Fgfr2 promoter activity in the presence of E12, a Twist binding partner.These data demonstrated that Twist1- and Twist2-haploinsufficiency caused reduced bone formation due to compromised FGF signaling.

  20. Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus.

    Science.gov (United States)

    Lappin, David F; Eapen, Bob; Robertson, Douglas; Young, Jenny; Hodge, Penny J

    2009-08-01

    To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. Plasma concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes.

  1. Hydroxyapatite coating for titanium fibre mesh scaffold enhances osteoblast activity and bone tissue formation.

    Science.gov (United States)

    Hirota, Makoto; Hayakawa, Tohru; Yoshinari, Masao; Ametani, Akihiro; Shima, Takaki; Monden, Yuka; Ozawa, Tomomichi; Sato, Mitsunobu; Koyama, Chika; Tamai, Naoto; Iwai, Toshinori; Tohnai, Iwai

    2012-10-01

    This study investigated the bone regeneration properties of titanium fibre mesh as a tissue engineering material. A thin hydroxyapatite (HA) coating on the titanium fibre web was created using the developed molecular precursor method without losing the complex interior structure. HA-coated titanium fibre mesh showed apatite crystal formation in vitro in a human osteoblast culture. Titanium fibre mesh discs with or without a thin HA coating were implanted into rat cranial bone defects, and the animals were killed at 2 and 4 weeks. The in vivo experience revealed that the amount of newly formed bone was significantly higher in the HA-coated titanium fibre mesh than in the non-coated titanium fibre mesh 2 weeks after implantation. These results suggest that thin HA coating enhances osteoblast activity and bone regeneration in the titanium fibre mesh scaffold. Thin HA-coating improved the ability of titanium fibre mesh to act as a bone regeneration scaffold. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation

    Science.gov (United States)

    Yukita, Akira; Yoshiba, Kunihiko; Yoshiba, Nagako; Takahashi, Masafumi; Nakamura, Hiroaki

    2012-01-01

    Dental pulp is involved in the formation of bone-like tissue in response to external stimuli. However, the origin of osteoblast-like cells constructing this tissue and the mechanism of their induction remain unknown. We therefore evaluated pulp mineralization induced by transplantation of a green fluorescent protein (GFP)–labeled tooth into a GFP-negative hypodermis of host rats. Five days after the transplantation, the upper pulp cavity became necrotic; however, cell-rich hard tissue was observed adjacent to dentin at the root apex. At 10 days, woven bone-like tissue was formed apart from the dentin in the upper pulp. After 20 days, these hard tissues expanded and became histologically similar to bone. GFP immunoreactivity was detected in the hard tissue-forming cells within the root apex as well as in the upper pulp. Furthermore, immunohistochemical observation of α–smooth muscle actin, a marker for undifferentiated cells, showed a positive reaction in cells surrounding this bone-like tissue within the upper pulp but not in those within the root apex. Immunoreactivities of Smad4, Runx2, and Osterix were detected in the hard tissue-forming cells within both areas. These results collectively suggest that the dental pulp contains various types of osteoblast progenitors and that these cells might thus induce bone-like tissue in severely injured pulp. PMID:22899860

  3. Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering.

    Science.gov (United States)

    Scotti, Celeste; Tonnarelli, Beatrice; Papadimitropoulos, Adam; Scherberich, Arnaud; Schaeren, Stefan; Schauerte, Alexandra; Lopez-Rios, Javier; Zeller, Rolf; Barbero, Andrea; Martin, Ivan

    2010-04-20

    Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, i.e., via remodeling of hypertrophic cartilaginous templates. To date, endochondral bone formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from bone marrow-derived, adult human MSC with an intrinsic capacity to undergo endochondral ossification. By analogy to embryonic limb development, we hypothesized that successful execution of the endochondral program depends on the initial formation of hypertrophic cartilaginous templates. Human MSC, subcutaneously implanted into nude mice at various stages of chondrogenic differentiation, formed bone trabeculae only when they had developed in vitro hypertrophic tissue structures. Advanced maturation in vitro resulted in accelerated formation of larger bony tissues. The underlying morphogenetic process was structurally and molecularly similar to the temporal and spatial progression of limb bone development in embryos. In particular, Indian hedgehog signaling was activated at early stages and required for the in vitro formation of hypertrophic cartilage. Subsequent development of a bony collar in vivo was followed by vascularization, osteoclastic resorption of the cartilage template, and appearance of hematopoietic foci. This study reveals the capacity of human MSC to generate bone tissue via an endochondral program and provides a valid model to study mechanisms governing bone development. Most importantly, this process could generate advanced grafts for bone regeneration by invoking a "developmental engineering" paradigm.

  4. Differential magnesium implant corrosion coat formation and contribution to bone bonding.

    Science.gov (United States)

    Rahim, Muhammad Imran; Weizbauer, Andreas; Evertz, Florian; Hoffmann, Andrea; Rohde, Manfred; Glasmacher, Birgit; Windhagen, Henning; Gross, Gerhard; Seitz, Jan-Marten; Mueller, Peter P

    2017-03-01

    Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels. Similarly, in soft tissue no bone induction by metallic magnesium or by the corrosion product magnesium hydroxide could be observed in a mouse model. Motivated by the comparatively rapid accumulation solid corrosion products physicochemical processes were examined as an alternative mechanism to explain the stimulation of bone growth by magnesium-based implants. During exposure to physiological solutions a structured corrosion coat formed on magnesium whereby the elements calcium and phosphate were enriched in the outermost layer which could play a role in the established biocompatible behavior of magnesium implants. When magnesium pins were inserted into avital bones, corrosion lead to increases in the pull out force, suggesting that the expanding corrosion layer was interlocking with the surrounding bone. Since mechanical stress is a well-established inducer of bone growth, volume increases caused by the rapid accumulation of corrosion products and the resulting force development could be a key mechanism and provide an explanation for the observed stimulatory effects of magnesium-based implants in hard tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 697-709, 2017. © 2016 Wiley Periodicals, Inc.

  5. Rapid prototyping: porous titanium alloy scaffolds produced by selective laser melting for bone tissue engineering.

    Science.gov (United States)

    Warnke, Patrick H; Douglas, Timothy; Wollny, Patrick; Sherry, Eugene; Steiner, Martin; Galonska, Sebastian; Becker, Stephan T; Springer, Ingo N; Wiltfang, Jörg; Sivananthan, Sureshan

    2009-06-01

    Selective laser melting (SLM), a method used in the nuclear, space, and racing industries, allows the creation of customized titanium alloy scaffolds with highly defined external shape and internal structure using rapid prototyping as supporting external structures within which bone tissue can grow. Human osteoblasts were cultured on SLM-produced Ti6Al4V mesh scaffolds to demonstrate biocompatibility using scanning electron microscopy (SEM), fluorescence microscopy after cell vitality staining, and common biocompatibility tests (lactate dihydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), 5-bromo-2-deoxyuridine (BrdU), and water soluble tetrazolium (WST)). Cell occlusion of pores of different widths (0.45-1.2 mm) was evaluated. Scaffolds were tested for resistance to compressive force. SEM investigations showed osteoblasts with well-spread morphology and multiple contact points. Cell vitality staining and biocompatibility tests confirmed osteoblast vitality and proliferation on the scaffolds. Pore overgrowth increased during 6 weeks' culture at pore widths of 0.45 and 0.5 mm, and in the course of 3 weeks for pore widths of 0.55, 0.6, and 0.7 mm. No pore occlusion was observed on pores of width 0.9-1.2 mm. Porosity and maximum compressive load at failure increased and decreased with increasing pore width, respectively. In summary, the scaffolds are biocompatible, and pore width influences pore overgrowth, resistance to compressive force, and porosity.

  6. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jun-Oh; Lee, Yong Deok; Kim, Haemin; Kim, Min Kyung; Song, Min-Kyoung; Lee, Zang Hee; Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr

    2016-09-02

    Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

  7. Activation of the Hh pathway in periosteum-derived mesenchymal stem cells induces bone formation in vivo: implication for postnatal bone repair.

    Science.gov (United States)

    Wang, Qun; Huang, Chunlan; Zeng, Fanjie; Xue, Ming; Zhang, Xinping

    2010-12-01

    While the essential role of periosteum in cortical bone repair and regeneration is well established, the molecular pathways that control the early osteogenic and chondrogenic differentiation of periosteal stem/progenitor cells during repair processes are unclear. Using a murine segmental bone graft transplantation model, we isolated a population of early periosteum-callus-derived mesenchymal stem cells (PCDSCs) from the healing autograft periosteum. These cells express typical mesenchymal stem cell markers and are capable of differentiating into osteoblasts, adipocytes, and chondrocytes. Characterization of these cells demonstrated that activation of the hedgehog (Hh) pathway effectively promoted osteogenic and chondrogenic differentiation of PCDSCs in vitro and induced bone formation in vivo. To determine the role of the Hh pathway in adult bone repair, we deleted Smoothened (Smo), the receptor that transduces all Hh signals at the onset of bone autograft repair via a tamoxifen-inducible RosaCreER mouse model. We found that deletion of Smo markedly reduced osteogenic differentiation of isolated PCDSCs and further resulted in a near 50% reduction in periosteal bone callus formation at the cortical bone junction as determined by MicroCT and histomorphometric analyses. These data strongly suggest that the Hh pathway plays an important role in adult bone repair via enhancing differentiation of periosteal progenitors and that activation of the Hh pathway at the onset of healing could be beneficial for repair and regeneration.

  8. Cone-beam computed tomography evaluation of dental, skeletal, and alveolar bone changes associated with bonded rapid maxillary expansion

    Directory of Open Access Journals (Sweden)

    Namrata Dogra

    2016-01-01

    Full Text Available Aims and Objectives: To evaluate skeletal changes in maxilla and its surrounding structures, changes in the maxillary dentition and maxillary alveolar bone changes produced by bonded rapid maxillary expansion (RME using cone-beam computed tomography (CBCT. Materials and Methods: The sample consisted of 10 patients (6 males and 4 females with age range 12 to 15 years treated with bonded RME. CBCT scans were performed at T1 (pretreatment and at T2 (immediately after expansion to evaluate the dental, skeletal, and alveolar bone changes. Results: RME treatment increased the overall skeletal parameters such as interorbital, zygomatic, nasal, and maxillary widths. Significant increases in buccal maxillary width was observed at first premolar, second premolar, and first molar level. There was a significant increase in arch width both on the palatal side and on the buccal side. Significant tipping of right and left maxillary first molars was seen. There were significant reductions in buccal bone plate thickness and increase in palatal bone plate thickness. Conclusions: Total expansion achieved with RME was a combination of dental, skeletal and alveolar bone changes. At the first molar level, 28.45% orthopedic, 16.03% alveolar bone bending, and 55.5% orthodontic changes were observed.

  9. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

    Science.gov (United States)

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods

  10. Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium.

    Science.gov (United States)

    Rakian, Audrey; Yang, Wu-Chen; Gluhak-Heinrich, Jelica; Cui, Yong; Harris, Marie A; Villarreal, Demitri; Feng, Jerry Q; Macdougall, Mary; Harris, Stephen E

    2013-06-01

    Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey's fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp7(+) (Osterix(+)) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and α-SMA(+) cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKO(Sp7-Cre-EGFP). Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKO(Sp7-Cre-EGFP). These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

  11. Craniosynostosis-Associated Fgfr2C342Y Mutant Bone Marrow Stromal Cells Exhibit Cell Autonomous Abnormalities in Osteoblast Differentiation and Bone Formation

    Directory of Open Access Journals (Sweden)

    J. Liu

    2013-01-01

    Full Text Available We recently reported that cranial bones of craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of mice. These results demonstrate that marrow stromal cells of mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the mutation influences both the axial and appendicular skeletons.

  12. Increase of homogenous new bone formation using osteoinductive factor rhGDF-5 during sinus floor augmentation in Goettingen Minipigs.

    Science.gov (United States)

    Brockmeyer, Phillipp; Lange, Katharina; Hahn, Wolfram; Schliephake, Henning; Matthias Gruber, Rudolf

    2015-11-01

    The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) induces an increased and homogenous distribution of new bone formation across the entire volume of sinus floor augmentation in 12 Goettingen Minipigs. In a randomized split-mouth design, one maxillary sinus was augmented with the bone substitute β-TCP, whereas a combination of β-TCP and the osteoinductive growth factor rhGDF-5 was used on the contralateral side. To evaluate the influence of dose and time on the effectiveness of the factor, two different concentrations of rhGDF-5 (400 μg and 800 μg) and healing periods (4 and 12 weeks) were each analysed. After 4 weeks, a homogenous gradient of bone formation could be observed for all dosage groups, with decreasing bone density from the local bone towards the sinus membrane. Both test groups, however, achieved a higher total level of bone formation compared with the control group, which was only significant in the low-dose group (P = 0.0184). After 12 weeks, the influence of the growth factor significantly depends on the region (P = 0.023). In the low-dose group, the new bone formation did not differ significantly within the examined regions of the graft (P = 0.1118), suggesting a homogeneous bone formation over the entire augmentation. The gradient of the high-dose group was similar to the control group with a decrease of local bone development. rhGDF-5 delivered on a β-TCP scaffold material leads to an increase in homogeneous new bone formation across the entire volume of the sinus floor augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

    Directory of Open Access Journals (Sweden)

    Grażyna E Sroga

    Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

  14. EPO Promotes Bone Repair through Enhanced Cartilaginous Callus Formation and Angiogenesis

    Science.gov (United States)

    Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

    2014-01-01

    Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration. PMID:25003898

  15. Increased PLEKHO1 within osteoblasts suppresses Smad-dependent BMP signaling to inhibit bone formation during aging.

    Science.gov (United States)

    Liu, Jin; Liang, Chao; Guo, Baosheng; Wu, Xiaohao; Li, Defang; Zhang, Zongkang; Zheng, Kang; Dang, Lei; He, Xiaojuan; Lu, Changwei; Peng, Songlin; Pan, Xiaohua; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

    2017-04-01

    Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging-associated diseases. Smad-dependent canonical BMP signaling pathway is indispensable for osteoblastic bone formation, which could be disrupted by the ubiquitination and subsequent proteasomal degradation of Smad1/5, the key molecules for BMP signaling transduction. However, whether the dysregulation of Smad1/5 ubiquitination and disrupted BMP signaling pathway is responsible for the age-related bone formation reduction is still underexplored. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) is a previously identified ubiquitination-related molecule that could specifically target the linker region between the WW domains of Smurf1 to promote the ubiquitination of Smad1/5. Here, we found an age-related increase in the expression of PLEKHO1 in bone specimens from either fractured patients or aging rodents, which was associated with the age-related reduction in Smad-dependent BMP signaling and bone formation. By genetic approach, we demonstrated that loss of Plekho1 in osteoblasts could promote the Smad-dependent BMP signaling and alleviated the age-related bone formation reduction. In addition, osteoblast-specific Smad1 overexpression had beneficial effect on bone formation during aging, which could be counteracted after overexpressing Plekho1 within osteoblasts. By pharmacological approach, we showed that osteoblast-targeted Plekho1 siRNA treatment could enhance Smad-dependent BMP signaling and promote bone formation in aging rodents. Taken together, it suggests that the increased PLEKHO1 could suppress Smad-dependent BMP signaling to inhibit bone formation during aging, indicating the translational potential of targeting PLEKHO1 in osteoblast as a novel bone anabolic strategy for reversing established osteoporosis during aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  16. Formation of thermal fatigue cracks in periodic rapid quenching of metal

    Energy Technology Data Exchange (ETDEWEB)

    Ots, A. [Tallinn Technical University, Thermal Engineering Department, Tallinn (Estonia)

    1998-12-31

    Water lancing is an effective technique for cleaning boiler heating surfaces from ash deposits by burning low-grade fuels with complicated composition of mineral matter. In water cleaning cycles of boiler`s heat transfer surfaces due to rapid quenching destruction of corrosion protective oxide film and formation of thermal fatigue cracks on the outer surface of the tube`s metal occur. The criterion of the thermal fatigue cracks` formation and their growth intensity depend on the character of temperature field in the tube`s metal outer layer. The solution of non-stationary heat conductivity equation for metal rapid quenching conditions is given. The convective heat transfer coefficients from hot metal surface to water jet were established experimentally. Thermal fatigue crack growth intensity was investigated in real boilers` heat transfer surfaces` tubes as well as in laboratory conditions. The formula for predicting thermal fatigue cracks` depth depending on the number of cleaning cycles. (orig.) 5 refs.

  17. Effects of Recombinant Human Bone Morphogenetic Protein-2 Dose and Ceramic Composition on New Bone Formation and Space Maintenance in a Canine Mandibular Ridge Saddle Defect Model.

    Science.gov (United States)

    Talley, Anne D; Kalpakci, Kerem N; Shimko, Daniel A; Zienkiewicz, Katarzyna J; Cochran, David L; Guelcher, Scott A

    2016-03-01

    Treatment of mandibular osseous defects is a significant clinical challenge. Maintenance of the height and width of the mandibular ridge is essential for placement of dental implants and restoration of normal dentition. While guided bone regeneration using protective membranes is an effective strategy for maintaining the anatomic contour of the ridge and promoting new bone formation, complications have been reported, including wound failure, seroma, and graft exposure leading to infection. In this study, we investigated injectable low-viscosity (LV) polyurethane/ceramic composites augmented with 100 μg/mL (low) or 400 μg/mL (high) recombinant human bone morphogenetic protein-2 (rhBMP-2) as space-maintaining bone grafts in a canine mandibular ridge saddle defect model. LV grafts were injected as a reactive paste that set in 5-10 min to form a solid porous composite with bulk modulus exceeding 1 MPa. We hypothesized that compression-resistant LV grafts would enhance new bone formation and maintain the anatomic contour of the mandibular ridge without the use of protective membranes. At the rhBMP-2 dose recommended for the absorbable collagen sponge carrier in dogs (400 μg/mL), LV grafts maintained the width and height of the host mandibular ridge and supported new bone formation, while at suboptimal (100 μg/mL) doses, the anatomic contour of the ridge was not maintained. These findings indicate that compression-resistant bone grafts with bulk moduli exceeding 1 MPa and rhBMP-2 doses comparable to that recommended for the collagen sponge carrier support new bone formation and maintain ridge height and width in mandibular ridge defects without protective membranes.

  18. p53 Regulates Bone Differentiation and Osteosarcoma Formation | Center for Cancer Research

    Science.gov (United States)

    Osteosarcoma is an uncommon cancer that usually begins in the large bones of the arm or leg, but is the second leading cause of cancer-related death in children and young adults. The tumor suppressor protein, p53, appears to be an important player in osteosarcomagenesis in part because these cancers are one of the most common to develop in patients with Li-Fraumeni syndrome, which is caused by an inherited mutation in p53. However, the precise role of p53 in osteosarcoma development has not been established. To begin investigating its importance to the formation of normal bone and osteosarcomas, Jing Huang, Ph.D., of CCR’s Laboratory of Cancer Biology and Genetics, and his colleagues, isolated bone marrow-derived mesenchymal stem cells (BMSCs) from p53 wild type (WT) and knock out (KO) mice using a recently validated approach. Because BMSCs are one of the cells-of-origin of osteosarcoma, they serve as a useful model system. BMSCs contain a subset of multipotent stem cells that can differentiate into several cell types, including osteoblasts, and are important mediators of bone homeostasis.

  19. Formation and Device Application of Ge Nanowire Heterostructures via Rapid Thermal Annealing

    OpenAIRE

    Tang, Jianshi; Wang, Chiu-Yen; Xiu, Faxian; Zhou, Yi; Chen, Lih-Juann; Wang, Kang L.

    2011-01-01

    We reviewed the formation of Ge nanowire heterostructure and its field-effect characteristics by a controlled reaction between a single-crystalline Ge nanowire and Ni contact pads using a facile rapid thermal annealing process. Scanning electron microscopy and transmission electron microscopy demonstrated a wide temperature range of 400~500°C to convert the Ge nanowire to a single-crystalline Ni2Ge/Ge/Ni2Ge nanowire heterostructure with atomically sharp interfaces. More importantly, we studie...

  20. Structure and formation of the twisted plywood pattern of collagen fibrils in rat lamellar bone.

    Science.gov (United States)

    Yamamoto, Tsuneyuki; Hasegawa, Tomoka; Sasaki, Muneteru; Hongo, Hiromi; Tabata, Chihiro; Liu, Zhusheng; Li, Minqi; Amizuka, Norio

    2012-04-01

    This study was designed to elucidate details of the structure and formation process of the alternate lamellar pattern known to exist in lamellar bone. For this purpose, we examined basic internal lamellae in femurs of young rats by transmission and scanning electron microscopy, the latter employing two different macerations with NaOH at concentrations of 10 and 24%. Observations after the maceration with 10% NaOH showed that the regular and periodic rotation of collagen fibrils caused an alternation between two types of lamellae: one consisting of transversely and nearly transversely cut fibrils, and the other consisting of longitudinally and nearly longitudinally cut fibrils. This finding confirms the consistency of the twisted plywood model. The maceration method with 24% NaOH removed bone components other than cells, thus allowing for three-dimensional observations of osteoblast morphology. Osteoblasts extended finger-like processes paralleling the inner bone surface, and grouped in such a way that, within a group, the processes arranged in a similar direction. Transmission electron microscopy showed that newly deposited fibrils were arranged alongside these processes. For the formation of the alternating pattern, our findings suggest that: (1) osteoblasts control the collagen fibril arrangement through their finger-like process position; (2) osteoblasts behave similarly within a group; (3) osteoblasts move their processes synchronously and periodically to promote alternating different fibril orientation; and (4) this dynamic sequential deposition of fibrils results in the alternate lamellar (or twisted plywood) pattern.

  1. Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

    Science.gov (United States)

    Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

    2017-09-01

    It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

  2. Influence of cooling rate on microstructure formation during rapid solidification of binary TiAl alloys

    Energy Technology Data Exchange (ETDEWEB)

    Kenel, C., E-mail: Christoph.Kenel@empa.ch; Leinenbach, C.

    2015-07-15

    Highlights: • Rapid solidification studies with varying cooling rates were realized for Ti–Al. • Experiments were combined with finite element simulations of heat transfer. • The resulting microstructure of Ti–Al alloys is strongly dependent on the Al content. • The microstructure and phase transformation behavior can be predicted. • The method allows alloy development for processes involving rapid solidification. - Abstract: Titanium aluminides as structural intermetallics are possible candidates for a potential weight reduction and increased performance of high temperature components. A method for the characterization of the microstructure formation in rapidly solidified alloys was developed and applied for binary Ti–(44–48)Al (at.%). The results show a strong dependency of the microstructure on the Al content at cooling rates between 6 ⋅ 10{sup 2} and 1.5 ⋅ 10{sup 4} K s{sup −1}. The formation of α → α{sub 2} ordering, lamellar α{sub 2} + γ colonies and interdendritic TiAl γ-phase were observed, depending on the Al amount. Based on thermodynamic calculations the observed microstructure can be explained using the CALPHAD approach taking into account the non-equilibrium conditions. The presented method provides a useful tool for alloy development for processing techniques involving rapid solidification with varying cooling rates.

  3. Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

    Science.gov (United States)

    Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

    2014-01-01

    Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

  4. Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.

    Science.gov (United States)

    Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

    2014-01-01

    Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration.

  5. Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

    Directory of Open Access Journals (Sweden)

    Kang-Yung Peng

    2011-01-01

    Full Text Available The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX mice. Microcomputed tomography (μCT analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD, trabecular bone volume/total volume (BV/TV, and trabecular bone number (Tb.N in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.

  6. Bone morphogenetic protein-induced inflammatory cyst formation after lumbar fusion causing nerve root compression.

    Science.gov (United States)

    Choudhry, Osamah J; Christiano, Lana D; Singh, Rahul; Golden, Barbara M; Liu, James K

    2012-03-01

    Bone morphogenetic protein (BMP) has been reported to cause early inflammatory changes, ectopic bony formation, adjacent level fusion, radiculitis, and osteolysis. The authors describe the case of a patient who developed inflammatory fibroblastic cyst formation around the BMP sponge after a lumbar fusion, resulting in compressive lumbar radiculopathy. A 70-year-old woman presented with left L-4 and L-5 radiculopathy caused by a Grade I spondylolisthesis with a left herniated disc at L4-5. She underwent a minimally invasive transforaminal lumbar interbody fusion with BMP packed into the interbody cage at L4-5. Her neurological symptoms resolved immediately postoperatively. Six weeks later, the patient developed recurrence of radiculopathy. Radiological imaging demonstrated an intraspinal cyst with a fluid-fluid level causing compression of the left L-4 and L-5 nerve roots. Reexpoloration of the fusion was performed, and a cyst arising from the posterior aspect of the cage was found to compress the axilla of the left L-4 nerve root and the shoulder of the L-5 nerve root. The cyst was decompressed, and the wall was partially excised. A collagen BMP sponge was found within the cyst and was removed. Postoperatively, the patient's radiculopathy resolved and she went on to achieve interbody fusion. Bone morphogenetic protein can be associated with inflammatory cyst formation resulting in neural compression. Spine surgeons should be aware of this complication in addition to the other reported BMP-related complications.

  7. Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.

    Science.gov (United States)

    Dai, Zhijie; Chung, Sookja K; Miao, Dengshun; Lau, Kam S; Chan, Alfred W H; Kung, Annie W C

    2011-03-01

    myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. Copyright © 2011 American Society for Bone and Mineral Research.

  8. Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts.

    Directory of Open Access Journals (Sweden)

    Marion David

    2010-03-01

    Full Text Available Bone metastases are highly frequent complications of breast cancers. Current bone metastasis treatments using powerful anti-resorptive agents are only palliative indicating that factors independent of bone resorption control bone metastasis progression. Autotaxin (ATX/NPP2 is a secreted protein with both oncogenic and pro-metastatic properties. Through its lysosphospholipase D (lysoPLD activity, ATX controls the level of lysophosphatidic acid (LPA in the blood. Platelet-derived LPA promotes the progression of osteolytic bone metastases of breast cancer cells. We asked whether ATX was involved in the bone metastasis process. We characterized the role of ATX in osteolytic bone metastasis formation by using genetically modified breast cancer cells exploited on different osteolytic bone metastasis mouse models.Intravenous injection of human breast cancer MDA-B02 cells with forced expression of ATX (MDA-B02/ATX to immunodeficiency BALB/C nude mice enhanced osteolytic bone metastasis formation, as judged by increased bone loss, tumor burden, and a higher number of active osteoclasts at the metastatic site. Mouse breast cancer 4T1 cells induced the formation of osteolytic bone metastases after intracardiac injection in immunocompetent BALB/C mice. These cells expressed active ATX and silencing ATX expression inhibited the extent of osteolytic bone lesions and decreased the number of active osteoclasts at the bone metastatic site. In vitro, osteoclast differentiation was enhanced in presence of MDA-B02/ATX cell conditioned media or recombinant autotaxin that was blocked by the autotaxin inhibitor vpc8a202. In vitro, addition of LPA to active charcoal-treated serum restored the capacity of the serum to support RANK-L/MCSF-induced osteoclastogenesis.Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a factor that stimulates directly cancer growth and metastasis, and

  9. Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures.

    Science.gov (United States)

    Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping

    2017-04-01

    Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells: coordinated activation of bone formation and resorption.

    Science.gov (United States)

    Nagata, Masaki; Hoshina, Hideyuki; Li, Minqi; Arasawa, Megumi; Uematsu, Kohya; Ogawa, Shin; Yamada, Kazuho; Kawase, Tomoyuki; Suzuki, Kenji; Ogose, Akira; Fuse, Ichiro; Okuda, Kazuhiro; Uoshima, Katsumi; Nakata, Koh; Yoshie, Hiromasa; Takagi, Ritsuo

    2012-05-01

    In ongoing clinical research into the use of cultured autogenous periosteal cells (CAPCs) in alveolar bone regeneration, CAPCs were grafted into 33 sites (15 for alveolar ridge augmentation and 18 for maxillary sinus lift) in 25 cases. CAPCs were cultured for 6weeks, mixed with particulate autogenous bone and platelet-rich plasma, and then grafted into the sites. Clinical outcomes were determined from high-resolution three-dimensional computed tomography (3D-CT) images and histological findings. No serious adverse events were attributable to the use of grafted CAPCs. Bone regeneration was satisfactory even in cases of advanced atrophy of the alveolar process. Bone biopsy after bone grafting with CAPCs revealed prominent recruitment of osteoblasts and osteoclasts accompanied by angiogenesis around the regenerated bone. 3D-CT imaging suggested that remodeling of the grafted autogenous cortical bone particles was faster in bone grafting with CAPCs than in conventional bone grafting. The use of CAPCs offers cell-based bone regeneration therapy, affording complex bone regeneration across a wide area, and thus expanding the indications for dental implants. Also, it enables the content of particulate autogenous bone in the graft material to be reduced to as low as 40%, making the procedure less invasive, or enabling larger amounts of graft materials to be prepared. It may also be possible to dispense with the use of autogenous bone altogether in the future. The results suggest that CAPC grafting induces bone remodeling, thereby enhancing osseointegration and consequently reducing postoperative waiting time after dental implant placement. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model

    Science.gov (United States)

    Lopez, Maria de Almeida; Olate, Sergio; Lanata-Flores, Antonio; Pozzer, Leandro; Cavalieri-Pereira, Lucas; Cantín, Mario; Vásquez, Bélgica; de Albergaria-Barbosa, José

    2013-01-01

    The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non-absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey’s test, considering statistical significance when p0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects. PMID:24228090

  12. CAD/CAM and rapid prototyped scaffold construction for bone regenerative medicine and surgical transfer of virtual planning: a pilot study.

    Science.gov (United States)

    Ciocca, L; De Crescenzio, F; Fantini, M; Scotti, R

    2009-01-01

    We developed a model to test new bone constructs to replace spare skeletal segments originating from new generation scaffolds for bone marrow-derived mesenchymal stem cells. Using computed tomography (CT) data, scaffolds were defined using computer-aided design/computer-aided manufacturing (CAD/CAM) for rapid prototyping by three-dimensional (3D) printing. A bone defect was created in pig mandible ramus by condyle resection for CT and CAD/CAM elaboration of bone volume for cutting and scaffold restoration. The protocol produced a perfect-fitting bone substitute model for rapid prototyped hydroxyapatite (HA) scaffolds. A surgical guide system was developed to accurately reproduce virtually planned bone sectioning procedures in animal models to obtain a perfect fit during surgery.

  13. Rapidly-Deposited Polydopamine Coating via High Temperature and Vigorous Stirring: Formation, Characterization and Biofunctional Evaluation

    Science.gov (United States)

    Zhou, Ping; Deng, Yi; Lyu, Beier; Zhang, Ranran; Zhang, Hai; Ma, Hongwei; Lyu, Yalin; Wei, Shicheng

    2014-01-01

    Polydopamine (PDA) coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces. PMID:25415328

  14. Rapidly-deposited polydopamine coating via high temperature and vigorous stirring: formation, characterization and biofunctional evaluation.

    Directory of Open Access Journals (Sweden)

    Ping Zhou

    Full Text Available Polydopamine (PDA coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces.

  15. Alloy composition dependence of formation of porous Ni prepared by rapid solidification and chemical dealloying

    Energy Technology Data Exchange (ETDEWEB)

    Qi Zhen [Key Laboratory of Liquid Structure and Heredity of Materials, Shandong University, Jingshi Road 73, Jinan 250061 (China); Zhang Zhonghua [Key Laboratory of Liquid Structure and Heredity of Materials, Shandong University, Jingshi Road 73, Jinan 250061 (China)], E-mail: zh_zhang@sdu.edu.cn; Jia Haoling [Key Laboratory of Liquid Structure and Heredity of Materials, Shandong University, Jingshi Road 73, Jinan 250061 (China); Qu Yingjie [Shandong Labor Occupational Technology College, Jingshi Road 388, Jinan 250022 (China); Liu Guodong; Bian Xiufang [Key Laboratory of Liquid Structure and Heredity of Materials, Shandong University, Jingshi Road 73, Jinan 250061 (China)

    2009-03-20

    In this paper, the effect of alloy composition on the formation of porous Ni catalysts prepared by chemical dealloying of rapidly solidified Al-Ni alloys has been investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis and N{sub 2} adsorption experiments. The experimental results show that rapid solidification and alloy composition have a significant effect on the phase constituent and microstructure of Al-Ni alloys. The melt spun Al-20 at.% Ni alloy consists of {alpha}-Al, NiAl{sub 3} and Ni{sub 2}Al{sub 3}, while the melt spun Al-25 and 31.5 at.% Ni alloys comprise NiAl{sub 3} and Ni{sub 2}Al{sub 3}. Moreover, the formation and microstructure of the porous Ni catalysts are dependent upon the composition of the melt spun Al-Ni alloys. The morphology and size of Ni particles in the Ni catalysts inherit from those of grains in the melt spun Al-Ni alloys. Rapid solidification can extend the alloy composition of Al-Ni alloys suitable for preparation of the Ni catalysts, and obviously accelerate the dealloying process of the Al-Ni alloys.

  16. Thai traditional massage increases biochemical markers of bone formation in postmenopausal women: a randomized crossover trial.

    Science.gov (United States)

    Saetung, Sunee; Chailurkit, La-Or; Ongphiphadhanakul, Boonsong

    2013-03-25

    The effect of massage therapy on bone metabolism in adults has only scarcely been explored. In a randomized crossover trial, we investigated the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover. Forty-eight postmenopausal women participated in the study. All volunteers were randomized to a 2-hour session of Thai traditional massage twice a week for 4 weeks and a 4-week control period after a 2-week washout, or vice versa. Twenty-one subjects were allocated to receiving Thai traditional massage first, followed by the control period, while 27 were initially allocated to the control period. Serum P1NP increased significantly after Thai traditional massage (P women whose ages were in the middle and higher tertiles and whose heights were in the lower and middle tertiles (n = 22) had a 14.8 ± 3.3% increase in P1NP after massage (P women (n = 26). Thai traditional massage results in an increase in bone formation as assessed by serum P1NP, particularly in postmenopausal women who are older and have a smaller body build. Future studies with larger samples and additional design features are warranted. ClinicalTrials.gov : NCT01627028.

  17. Three-dimensional assessment of buccal alveolar bone after rapid and slow maxillary expansion: a clinical trial study.

    Science.gov (United States)

    Brunetto, Mauricio; Andriani, Juliana da Silva Pereira; Ribeiro, Gerson Luiz Ulema; Locks, Arno; Correa, Marcio; Correa, Letícia Ruhland

    2013-05-01

    The purposes of this study were to analyze and compare the immediate effects of rapid and slow maxillary expansion protocols, accomplished by Haas-type palatal expanders activated in different frequencies of activation on the positioning of the maxillary first permanent molars and on the buccal alveolar bones of these teeth with cone-beam computerized tomography. The sample consisted of 33 children (18 girls, 15 boys; mean age, 9 years) randomly distributed into 2 groups: rapid maxillary expansion (n = 17) and slow maxillary expansion (n = 16). Patients in the rapid maxillary expansion group received 2 turns of activation (0.4 mm) per day, and those in the slow maxillary expansion group received 2 turns of activation (0.4 mm) per week until 8 mm of expansion was achieved in both groups. Cone-beam computerized tomography images were taken before treatment and after stabilization of the jackscrews. Data were gathered through a standardized analysis of cone-beam computerized tomography images. Intragroup statistical analysis was accomplished with the Wilcoxon matched-pairs test, and intergroup statistical analysis was accomplished with analysis of variance. Linear relationships, among all variables, were determined by Spearman correlation. Both protocols caused buccal displacement of the maxillary first permanent molars, which had more bodily displacement in the slow maxillary expansion group, whereas more inclination was observed in the rapid maxillary expansion group. Vertical and horizontal bone losses were found in both groups; however, the slow maxillary expansion group had major bone loss. Periodontal modifications in both groups should be carefully considered because of the reduction of spatial resolution in the cone-beam computerized tomography examinations after stabilization of the jackscrews. Modifications in the frequency of activation of the palatal expander might influence the dental and periodontal effects of palatal expansion. Copyright © 2013

  18. Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep.

    Science.gov (United States)

    Schneider, Oliver D; Mohn, Dirk; Fuhrer, Roland; Klein, Karina; Kämpf, Käthi; Nuss, Katja M R; Sidler, Michèle; Zlinszky, Katalin; von Rechenberg, Brigitte; Stark, Wendelin J

    2011-03-16

    The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

  19. Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis.

    Directory of Open Access Journals (Sweden)

    Melissa N van Tok

    Full Text Available Insulin like growth factor (IGF-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively.Mice overexpressing IGF-I in the osteoblast lineage (Ob-IGF-I+/- line 324-7 were studied during collagen induced arthritis and in the DBA/1 aging model for ankylosing enthesitis. Mice were scored clinically and peripheral joints were analysed histologically for the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts.90-100% of the mice developed CIA with no differences between the Ob-IGF-I+/- and non-transgenic littermates. Histological analysis revealed similar levels of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the ankle joints. In the DBA/1 aging model for ankylosing enthesitis 60% of the mice in both groups had a clinical score 1<. Severity was similar between both groups. Histological analysis revealed the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the toes in equal levels.Overexpression of IGF-I in the osteoblast lineage does not contribute to an increase in repair of erosions or syndesmophyte formation in mouse models for destructive and remodeling arthritis.

  20. Matrix Elasticity of Void-Forming Hydrogels Controls Transplanted Stem Cell-Mediated Bone Formation

    Science.gov (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T; Darnell, Max C; Desai, Rajiv; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N; Mooney, David J.

    2015-01-01

    The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate1. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype2–4. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials5–7, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ. PMID:26366848

  1. Differential actions of VEGF-A isoforms on perichondrial angiogenesis during endochondral bone formation.

    Science.gov (United States)

    Takimoto, Aki; Nishizaki, Yuriko; Hiraki, Yuji; Shukunami, Chisa

    2009-08-15

    During endochondral bone formation, vascular invasion initiates the replacement of avascular cartilage by bone. We demonstrate herein that the cartilage-specific overexpression of VEGF-A(164) in mice results in the hypervascularization of soft connective tissues away from cartilage. Unexpectedly, perichondrial tissue remained avascular in addition to cartilage. Hypervascularization of tissues similarly occurred when various VEGF-A isoforms were overexpressed in the chick forelimb, but also in this case perichondrial tissue and cartilage were completely devoid of vasculature. However, following bony collar formation, anti-angiogenic properties in perichondrial tissue were lost and perichondrial angiogenesis was accelerated by VEGF-A(146), VEGF-A(166), or VEGF-A(190). Once the perichondrium was vascularized, osteoclast precursors were recruited from the circulation and the induction of MMP9 and MMP13 can be observed in parallel with the activation of TGF-beta signaling. Neither perichondrial angiogenesis nor the subsequent cartilage vascularization was found to be accelerated by the non-heparin-binding VEGF-A(122) or by the VEGF-A(166)DeltaE(162)-R(166) mutant lacking a neuropilin-binding motif. Hence, perichondrial angiogenesis is a prerequisite for subsequent cartilage vascularization and is differentially regulated by VEGF-A isoforms.

  2. Dual Delivery of rhPDGF-BB and Bone Marrow Mesenchymal Stromal Cells Expressing the BMP2 Gene Enhance Bone Formation in a Critical-Sized Defect Model

    Science.gov (United States)

    Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo

    2013-01-01

    Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis. PMID:23901900

  3. Perinatal maternal dietary supplementation of ω3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring.

    Science.gov (United States)

    Fong, Laura; Muhlhausler, Beverly S; Gibson, Robert A; Xian, Cory J

    2012-05-01

    It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ω3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-κB ligand, TNF-α, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.

  4. Silorane resin supports proliferation, differentiation, and mineralization of MLO-A5 bone cells in vitro and bone formation in vivo.

    Science.gov (United States)

    Eick, J David; Barragan-Adjemian, Cielo; Rosser, Jennifer; Melander, Jennifer R; Dusevich, Vladimir; Weiler, Rachel A; Miller, Bradley D; Kilway, Kathleen V; Dallas, Mark R; Bi, Lianxing; Nalvarte, Elisabet L; Bonewald, Lynda F

    2012-04-01

    Methyl methacrylate used in bone cements has drawbacks of toxicity, high exotherm, and considerable shrinkage. A new resin, based on silorane/oxirane chemistry, has been shown to have little toxicity, low exotherm, and low shrinkage. We hypothesized that silorane-based resins may also be useful as components of bone cements as well as other bone applications and began testing on bone cell function in vitro and in vivo. MLO-A5, late osteoblast cells, were exposed to polymerized silorane (SilMix) resin (and a standard polymerized bisGMA/TEGDMA methacrylate (BT) resin and compared to culture wells without resins as control. A significant cytotoxic effect was observed with the BT resin resulting in no cell growth, whereas in contrast, SilMix resin had no toxic effects on MLO-A5 cell proliferation, differentiation, nor mineralization. The cells cultured with SilMix produced increasing amounts of alkaline phosphatase (1.8-fold) compared to control cultures. Compared to control cultures, an actual enhancement of mineralization was observed in the silorane resin-containing cultures at days 10 and 11 as determined by von Kossa (1.8-2.0 fold increase) and Alizarin red staining (1.8-fold increase). A normal bone calcium/phosphate atomic ratio was observed by elemental analysis along with normal collagen formation. When used in vivo to stabilize osteotomies, no inflammatory response was observed, and the bone continued to heal. In conclusion, the silorane resin, SilMix, was shown to not only be non cytototoxic, but actually supported bone cell function. Therefore, this resin has significant potential for the development of a nontoxic bone cement or bone stabilizer. Copyright © 2012 Wiley Periodicals, Inc.

  5. Effect of Different rhBMP-2 and TG-VEGF Ratios on the Formation of Heterotopic Bone and Neovessels

    Directory of Open Access Journals (Sweden)

    Wei Xin Cai

    2014-01-01

    Full Text Available Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2 and transglutamate vascular endothelial growth factor (TG-VEGF in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles.

  6. Synergistic Inhibition of Endochondral Bone Formation by Silencing Hif1α and Runx2 in Trauma-induced Heterotopic Ossification

    Science.gov (United States)

    Lin, Lin; Shen, Qi; Leng, Huijie; Duan, Xiaoning; Fu, Xin; Yu, Changlong

    2011-01-01

    Angiogenesis and osteogenesis are tightly coupled during bone development. We studied the effect of inhibition of Hif1α and Runt-related protein 2 (Runx2) on the formation of heterotopic ossification (HO). We constructed lentivirus vectors expressing Hif1α small interfering RNA (siRNA) and Runx2 siRNA. The inhibition of Hif1α function impaired osteoblast proliferation while osteoblasts differentiated normally. Osteoblasts lacking Runx2 proliferated normally while the differentiation was impaired. The osteoblast differentiation was significantly inhibited by co-Runx2 and Hif1α siRNA treatment. The formation of HO by inhibiting Runx2 and Hif1α in an animal model induced by Achilles tenotomy was investigated. The results showed that lacking of Runx2 and Hif1α could inhibit HO formation. Inhibition of Hif1α prevented HO formation only at the initial step and inhibition of Runx2 worked both at the initial step and after chondrogenesis. Angiogenesis and the expressions of osteogenic genes were downregulated in the Hif1α siRNA group. We found synergistic inhibition of endochondral bone formation by silencing Hif1α and Runx2. Our study provided new insight into the roles of Hif1α and Runx2 during the processes of endochondral bone formation, and had important implications for the new therapeutic methods to inhibit HO or to enhance bone formation. PMID:21629226

  7. Effect of recombinant PDGF-BB on bone formation in the presence of β-tricalcium phosphate and bovine bone mineral matrix: a pilot study in rat calvarial defects.

    Science.gov (United States)

    Luvizuto, Eloá R; Tangl, Stefan; Dobsak, Toni; Reich, Karoline; Gruber, Reinhard; Sonoda, Celso K; Okamoto, Roberta

    2016-05-04

    Supplementation of bone substitutes with recombinant platelet-derived growth factor-BB (PDGF-BB) can enhance bone regeneration. The aim of the study was to evaluate the effect of PDGF-BB on bone formation in the presence of β-tricalcium phosphate and bovine bone mineral matrix in a rat calvaria defect model. The authors examined 5 mm rat calvarial defects treated with β-tricalcium phosphate (TCP) or demineralized bovine bone mineral (DBBM) with and without 0.3 mg/ml recombinant PDGF-BB. Calvaria defects were randomly divided into the following treatment groups (n = 5); TCP; TCP plus PDGF-BB; DBBM; DBBM plus PDGF-BB; and untreated empty control. After 45 days, bone formation was evaluated by histomorphometry and fluorescence microscopy. The authors report that the area of newly formed bone was similar between the empty controls and the two bone substitutes, TCP and DBBM. Supplementation of TCP and DBBM with PDGF-BB had no significant impact on bone formation. Fluorochrome staining revealed no visible changes in the pattern of bone formation in defects filled with TCP and DBBM, irrespective of PDGF-BB. Furthermore, supplementation with PDGF-BB did not influence biomaterial degradation. The authors concluded that PDGF-BB had no impact on bone formation and degradation of bone substitutes in the respective rodent models. Thus, possible beneficial effects of PDGF-BB may require other model situations.

  8. The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation

    DEFF Research Database (Denmark)

    Hassager, C; Jensen, L T; Johansen, J S

    1991-01-01

    Seventy-nine osteoporotic (prior forearm or vertebral fracture), but otherwise healthy, postmenopausal women (aged 55 to 75 years) were allocated to two double-blind trials: (1) 39 women received either nandrolone decanoate (anabolic steroid) 50 mg as an intramuscular depot injection or a placebo...... = .6; P less than .001), but not with histomorphometrically measured bone resorption or biochemical estimates of bone resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen therapy significantly decreased (P less than .001) serum PICP by about 30%, whereas anabolic steroid...... therapy hardly affected it. We conclude that serum PICP may be used as a noninvasive measurement of bone formation on a group basis. Whereas bone formation is clearly decreased during estrogen-progestogen therapy, it is not affected by long-term therapy with anabolic steroids....

  9. Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Vikjaer, D; Blom, S; Hjørting-Hansen, E

    1997-01-01

    The effect of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on bone healing was examined in calvarial defects in rabbits. Bicortical circular (critical size) defects were prepared in the calvarial bone of 16 rabbits. The defects were closed on the dural side and covered externally...... with expanded polytetrafluoroethylene membranes to prevent interference with osteogenesis within the defect by the surrounding tissue and to keep the growth factor in place. A single dose of methylcellulose gel (4.4%) with (n = 8) or without rhPDGF-BB (50 micrograms/ml) (n = 8) was applied to the defects......, and the bone formation was evaluated after 8 weeks. Healing of defects in both groups was characterized by the presence of newly formed bone along the edges of the original defect and by a central area of fibrous connective tissue. The newly formed bone in the rhPDGF-BB treated defects had a trabecular...

  10. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K.; Zaher, Walid; Larsen, Kenneth Hauberg

    2015-01-01

    by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones. RESULTS: HBF clones were exhibited higher ex...

  11. In Vitro Biocompability/Osteogenesis and In Vivo Bone Formation Evalution of Peptide-Decorated Apatite Nanocomposites Assisted via Polydopamine.

    Science.gov (United States)

    Deng, Yi; Sun, Yuhua; Bai, Yanjie; Gao, Xiang; Zhang, Huan; Xu, Anxiu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2016-04-01

    Enhancing the biocompatibility and osteogenic activity of nano-apatite for applications in bone graft substitutes and bone tissue engineering have been the current challenge in regeneration of lost bone. Inspired by mussels, here we have developed facile biomimetic approaches for preparation of two types of peptide-conjugated apatite nanocompsoties assisted by polydopamine (pDA). We exploited polydopamine chemistry for the modification of nano-apatite crystals: polydopamine coated apatite (HA-c-pDA) and polydopamine template-mediated apatite (HA-t-pDA), on which bone forming peptide was subsequently immobilized under weakly basic conditions to obtain peptide-conjugated apatite nanocomposites (HA-c-pep and HA-t-pep, respectively). TEM images revealed that HA-c-pDA displayed typically rod-like morphology, while HA-t-pDA was sponge-like structure where pDA sheets were decorated by needle-like apatite crystals with low degree of crystallinity. In the cell culture experiments, HA-t-pep nanocomposite exhibited higher cell proliferation, spreading, and alkaline phosphatase activity as well as calcium nodule-formation, compared with pristine nano-HA and HA-c-pep nanocomposite. We then implanted the peptide-decorated apatite into rabbit calvarial defects and analyzed bone formation after 2 months. The data revealed that HA-t-pep group exhibited remarkably enhanced bioactivity and bone formation in vivo. Based on these results, our biomimetic approach could be a promising tool to develop peptide-conjugated apatites for bone regeneration. Meanwhile, the excellent biocompatibility and high osteogenesis of the peptide-conjugated apatite nanocomposite might confer its great potentials in bone repair, bone augmentation, as well as coating of biomedical implants.

  12. Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects.

    Science.gov (United States)

    Poudel, Sher Bahadur; Bhattarai, Govinda; Kook, Sung-Ho; Shin, Yun-Ji; Kwon, Tae-Ho; Lee, Seung-Youp; Lee, Jeong-Chae

    2017-10-01

    Transgenic plant cell suspension culture systems have been utilized extensively as convenient and efficient expression systems for the production of recombinant human growth factors. We produced insulin-like growth factor-1 using a plant suspension culture system (p-IGF-1) and explored its effect on new bone formation in calvarial defects. We also compared the bone regenerating potential of p-IGF-1 with commercial IGF-1 derived from Escherichia coli (e-IGF-1). Male C57BL/6 mice underwent calvarial defect surgery, and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 13μg of p-IGF-1 (p-IGF-1 group) or e-IGF-1 (e-IGF-1 group). The sham group did not receive any treatment with ACS or IGFs after surgery. Live μCT and histological analyses showed critical-sized bone defects in the sham group, whereas greater bone formation was observed in the p-IGF-1 and e-IGF-1 groups than the ACS group both 5 and 10weeks after surgery. Bone mineral density, bone volume, and bone surface values were also higher in the IGF groups than in the ACS group. Local delivery of p-IGF-1 or e-IGF-1 more greatly enhanced the expression of osteoblast-specific markers, but inhibited osteoclast formation, in newly formed bone compared with ACS control group. Specifically, p-IGF-1 treatment induced higher expression of alkaline phosphatase, osteocalcin, and osteopontin in the defect site than did e-IGF-1. Furthermore, treatment with p-IGF-1, but not e-IGF-1, increased mineralization of MC3T3-E1 cells, with the attendant upregulation of osteogenic marker genes. Collectively, our findings suggest the potential of p-IGF-1 in promoting the processes required for bone regeneration. Copyright © 2017. Published by Elsevier Ltd.

  13. Filaments in curved streamlines: rapid formation of Staphylococcus aureus biofilm streamers

    Science.gov (United States)

    Kim, Minyoung Kevin; Drescher, Knut; Pak, On Shun; Bassler, Bonnie L.; Stone, Howard A.

    2014-06-01

    Biofilms are surface-associated conglomerates of bacteria that are highly resistant to antibiotics. These bacterial communities can cause chronic infections in humans by colonizing, for example, medical implants, heart valves, or lungs. Staphylococcus aureus, a notorious human pathogen, causes some of the most common biofilm-related infections. Despite the clinical importance of S. aureus biofilms, it remains mostly unknown how physical effects, in particular flow, and surface structure influence biofilm dynamics. Here we use model microfluidic systems to investigate how environmental factors, such as surface geometry, surface chemistry, and fluid flow affect biofilm development of S. aureus. We discovered that S. aureus rapidly forms flow-induced, filamentous biofilm streamers, and furthermore if surfaces are coated with human blood plasma, streamers appear within minutes and clog the channels more rapidly than if the channels are uncoated. To understand how biofilm streamer filaments reorient in flows with curved streamlines to bridge the distances between corners, we developed a mathematical model based on resistive force theory of slender filaments. Understanding physical aspects of biofilm formation of S. aureus may lead to new approaches for interrupting biofilm formation of this pathogen.

  14. Filaments in curved flow: Rapid formation of Staphylococcus aureus biofilm streamers

    Science.gov (United States)

    Kim, Min Young; Drescher, Knut; Pak, On Shun; Bassler, Bonnie L.; Stone, Howard A.

    2014-03-01

    Biofilms are surface-associated conglomerates of bacteria that are highly resistant to antibiotics. These bacterial communities can cause chronic infections in humans by colonizing, for example, medical implants, heart valves, or lungs. Staphylococcus aureus, a notorious human pathogen, causes some of the most common biofilm-related infections. Despite the clinical importance of S. aureus biofilms, it remains mostly unknown how physical effects, in particular flow, and surface structure influence biofilm dynamics. Here we use model microfluidic systems to investigate how environmental factors, such as surface geometry, surface chemistry, and fluid flow affect biofilm development in S. aureus.We discovered that S. aureus rapidly forms flow-induced, filamentous biofilm streamers, and furthermore if surfaces are coated with human blood plasma, streamers appear within minutes and clog the channels more rapidly than if the channels are uncoated. To understand how biofilm streamer filaments reorient in curved flow to bridge the distances between corners, we developed a mathematical model based on resistive force theory and slender filaments. Understanding physical aspects of biofilm formation in S. aureus may lead to new approaches for interrupting biofilm formation of this pathogen.

  15. The rapid formation of a large rotating disk galaxy three billion years after the Big Bang.

    Science.gov (United States)

    Genzel, R; Tacconi, L J; Eisenhauer, F; Schreiber, N M Förster; Cimatti, A; Daddi, E; Bouché, N; Davies, R; Lehnert, M D; Lutz, D; Nesvadba, N; Verma, A; Abuter, R; Shapiro, K; Sternberg, A; Renzini, A; Kong, X; Arimoto, N; Mignoli, M

    2006-08-17

    Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

  16. Microstructure Formation and Resistivity Change in CuCr during Rapid Solidification

    Directory of Open Access Journals (Sweden)

    Ulla Hauf

    2017-11-01

    Full Text Available The formation of the surface-near microstructure after a current interruption of CuCr contact materials in a vacuum interrupter is characterized by a fast heating and subsequently rapid solidification process. In the present article, we reveal and analyse the formation of two distinct microstructural regions that result from the heat, which is generated and dissipated during interruption. In the topmost region, local and global texture, as well as the resulting microstructure, indicate that both Cu and Cr were melted during rapid heating and solidification whereas in the region underneath, only Cu was melted and elongated Cu-grains solidified with the <001>-direction perpendicularly aligned to the surface. By analysing the lattice parameter of the Cu solid solution, a supersaturation of the solid solution with about 2.25 at % Cr was found independent if Cu was melted solely or together with the Cr. The according reduction of electrical conductivity in the topmost region subsequent to current interruption and the resulting heat distribution are discussed based on these experimental results.

  17. Amorphous Phase Formation Analysis of Rapidly Solidified CoCr Droplets

    Science.gov (United States)

    Bogno, Abdoul-Aziz; Riveros, Carlos; Henein, Hani; Li, Delin

    2016-12-01

    This paper investigates amorphous phase formation and rapid solidification characteristics of a CoCr alloy. High cooling rate and high undercooling-induced rapid solidification of the alloy was achieved by impulse atomization in helium atmosphere. Two atomization experiments were carried out to generate powders of a wide size range from liquid CoCr at two different temperatures. Amorphous fraction and kinetic crystallization properties of impulse atomized powders were systematically quantified by means of differential scanning calorimetry. In addition, different but complementary characterization tools were used to analyze the powders microstructures. The fraction of amorphous phase within the investigated powders is found to be promoted by high cooling rate or smaller powder size. The critical cooling rate for amorphous phase formation, which is influenced by the oxygen content in the melt, is found to be 3 × 104 K s-1 and corresponds to a 160- µm-diameter powder atomized in helium. Hardness of the powders is found to follow a trend that is described by the Hall-Petch relation when a relatively high fraction of crystalline structures is present and decreases with the fraction of amorphous phase.

  18. Green tea polyphenols improve bone microarchitecture in high-fat-diet-induced obese female rats through suppressing bone formation and erosion.

    Science.gov (United States)

    Shen, Chwan-Li; Chyu, Ming-Chien; Cao, Jay J; Yeh, James K

    2013-05-01

    This study evaluates the effects of green tea polyphenols (GTPs) on bone microarchitecture in high-fat-diet (HFD)-induced obese female rats. Thirty-six 3-month-old female rats were fed either a control diet or a HFD for 4 months. Animals in the control group continued on the control diet for another 4 months. Animals in the HFD group were divided into two groups, with 0.5 g/100 mL GTP (the HFD+GTP group) or without GTP (the HFD group) in drinking water, in addition to the HFD for another 4 months. Compared to the control group, the HFD group increased bone formation and erosion rates at the tibia, decreased trabecular volume and thickness, but had no impact on bone mineral density (BMD), trabecular number (Tb.N), and separation. Compared to the control group, the HFD+GTP group demonstrates a greater Tb.N at the proximal tibia, and a greater trabecular thickness at the femur and the lumbar vertebrae, but a smaller trabecular separation (Tb.Sp) and mineralizing surface at the proximal tibia, and a reduced endocortical mineral apposition rate (MAR) at the tibia shaft. Relative to the HFD group, the HFD+GTP group demonstrates (1) a higher BMD at the femur, a greater trabecular volume, thickness, and number at the proximal tibia, a larger cortical area and thickness at the tibial shaft, and a greater trabecular volume and thickness at the femur and the lumbar vertebrae, (2) a smaller Tb.Sp, MAR, bone formation rate, and eroded surface at the tibia. We concluded that GTP supplementation in drinking water improves bone microarchitecture in the HFD-induced obese female rats, possibly through suppressing bone turnover, resulting in a larger net bone volume.

  19. Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study.

    Directory of Open Access Journals (Sweden)

    Karen N Borschmann

    Full Text Available Immobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans.To investigate the skeletal effect of middle cerebral artery occlusion (MCAo stroke in rats and examine its utility as a model of human post-stroke bone loss.Twenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV measured by Micro-CT (10.5 micron istropic voxel size at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and foot-faults and physical activity (cage monitoring were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX were assessed at baseline, and days 7 and 27.No effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046 at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9 and total volume (6.4%, IQR 1.2, 7.6 were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals.MCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.

  20. A systematic review of the effects of bone-borne surgical assisted rapid maxillary expansion.

    NARCIS (Netherlands)

    Verstraaten, J.; Kuijpers-Jagtman, A.M.; Mommaerts, M.Y.; Berge, S.J.; Nada, R.; Schols, J.G.J.H.

    2010-01-01

    INTRODUCTION: A systematic literature review was conducted to find out if bone-borne maxillary expansion with corticotomies is an effective and secure orthodontic/orthopaedic treatment modality, eliminating orthodontic and periodontal side effects of tooth-borne maxillary expansion with

  1. Camouflage treatment of skeletal class III malocclusion with asymmetry using a bone-borne rapid maxillary expander.

    Science.gov (United States)

    Seo, Yu-Jin; Chung, Kyu-Rhim; Kim, Seong-Hun; Nelson, Gerald

    2015-03-01

    This case report presents the successful use of palatal mini-implants for rapid maxillary expansion and mandibular distalization in a skeletal Class III malocclusion. The patient was a 13-year-old girl with the chief complaint of facial asymmetry and a protruded chin. Camouflage orthodontic treatment was chosen, acknowledging the possibility of need for orthognathic surgery after completion of her growth. A bone-borne rapid expander (BBRME) was used to correct the transverse discrepancy and was then used as indirect anchorage for distalization of the lower dentition with Class III elastics. As a result, a Class I occlusion with favorable inclination of the upper teeth was achieved without any adverse effects. The total treatment period was 25 months. Therefore, BBRME can be considered an alternative treatment in skeletal Class III malocclusion.

  2. Formation and Device Application of Ge Nanowire Heterostructures via Rapid Thermal Annealing

    Directory of Open Access Journals (Sweden)

    Jianshi Tang

    2011-01-01

    Full Text Available We reviewed the formation of Ge nanowire heterostructure and its field-effect characteristics by a controlled reaction between a single-crystalline Ge nanowire and Ni contact pads using a facile rapid thermal annealing process. Scanning electron microscopy and transmission electron microscopy demonstrated a wide temperature range of 400~500°C to convert the Ge nanowire to a single-crystalline Ni2Ge/Ge/Ni2Ge nanowire heterostructure with atomically sharp interfaces. More importantly, we studied the effect of oxide confinement during the formation of nickel germanides in a Ge nanowire. In contrast to the formation of Ni2Ge/Ge/Ni2Ge nanowire heterostructures, a segment of high-quality epitaxial NiGe was formed between Ni2Ge with the confinement of Al2O3 during annealing. A twisted epitaxial growth mode was observed in both two Ge nanowire heterostructures to accommodate the large lattice mismatch in the NixGe/Ge interface. Moreover, we have demonstrated field-effect transistors using the nickel germanide regions as source/drain contacts to the Ge nanowire channel. Our Ge nanowire transistors have shown a high-performance p-type behavior with a high on/off ratio of 105 and a field-effect hole mobility of 210 cm2/Vs, which showed a significant improvement compared with that from unreacted Ge nanowire transistors.

  3. Rapid formation of large dust grains in the luminous supernova 2010jl.

    Science.gov (United States)

    Gall, Christa; Hjorth, Jens; Watson, Darach; Dwek, Eli; Maund, Justyn R; Fox, Ori; Leloudas, Giorgos; Malesani, Daniele; Day-Jones, Avril C

    2014-07-17

    The origin of dust in galaxies is still a mystery. The majority of the refractory elements are produced in supernova explosions, but it is unclear how and where dust grains condense and grow, and how they avoid destruction in the harsh environments of star-forming galaxies. The recent detection of 0.1 to 0.5 solar masses of dust in nearby supernova remnants suggests in situ dust formation, while other observations reveal very little dust in supernovae in the first few years after explosion. Observations of the spectral evolution of the bright SN 2010jl have been interpreted as pre-existing dust, dust formation or no dust at all. Here we report the rapid (40 to 240 days) formation of dust in its dense circumstellar medium. The wavelength-dependent extinction of this dust reveals the presence of very large (exceeding one micrometre) grains, which resist destruction. At later times (500 to 900 days), the near-infrared thermal emission shows an accelerated growth in dust mass, marking the transition of the dust source from the circumstellar medium to the ejecta. This provides the link between the early and late dust mass evolution in supernovae with dense circumstellar media.

  4. Contribution of matrix vesicles and alkaline phosphatase to ectopic bone formation

    Directory of Open Access Journals (Sweden)

    P. Ciancaglini

    2006-05-01

    Full Text Available Endochondral calcification involves the participation of matrix vesicles (MVs, but it remains unclear whether calcification ectopically induced by implants of demineralized bone matrix also proceeds via MVs. Ectopic bone formation was induced by implanting rat demineralized diaphyseal bone matrix into the dorsal subcutaneous tissue of Wistar rats and was examined histologically and biochemically. Budding of MVs from chondrocytes was observed to serve as nucleation sites for mineralization during induced ectopic osteogenesis, presenting a diameter with Gaussian distribution with a median of 306 ± 103 nm. While the role of tissue-nonspecific alkaline phosphatase (TNAP during mineralization involves hydrolysis of inorganic pyrophosphate (PPi, it is unclear how the microenvironment of MV may affect the ability of TNAP to hydrolyze the variety of substrates present at sites of mineralization. We show that the implants contain high levels of TNAP capable of hydrolyzing p-nitrophenylphosphate (pNPP, ATP and PPi. The catalytic properties of glycosyl phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol-specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as substrates. While the enzymatic efficiency (k cat/Km remained comparable between polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi, respectively, compared to the membrane-bound enzyme. Our data are consistent with the involvement of MVs during ectopic calcification and also suggest that the location of TNAP on the membrane of MVs may play a role in determining substrate selectivity in this micro-compartment.

  5. Development of a rapid culture method to induce adipocyte differentiation of human bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ninomiya, Yuichi [Translational Research Center, Saitama International Medical, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Sugahara-Yamashita, Yzumi; Nakachi, Yutaka; Tokuzawa, Yoshimi; Okazaki, Yasushi [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241 (Japan); Nishiyama, Masahiko, E-mail: yamacho@saitama-med.ac.jp [Translational Research Center, Saitama International Medical, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan)

    2010-04-02

    Human mesenchymal stem cells (hMSCs) derived from bone marrow are multipotent stem cells that can regenerate mesenchymal tissues such as adipose, bone or muscle. It is thought that hMSCs can be utilized as a cell resource for tissue engineering and as human models to study cell differentiation mechanisms, such as adipogenesis, osteoblastogenesis and so on. Since it takes 2-3 weeks for hMSCs to differentiate into adipocytes using conventional culture methods, the development of methods to induce faster differentiation into adipocytes is required. In this study we optimized the culture conditions for adipocyte induction to achieve a shorter cultivation time for the induction of adipocyte differentiation in bone marrow-derived hMSCs. Briefly, we used a cocktail of dexamethasone, insulin, methylisobutylxanthine (DIM) plus a peroxisome proliferator-activated receptor {gamma} agonist, rosiglitazone (DIMRo) as a new adipogenic differentiation medium. We successfully shortened the period of cultivation to 7-8 days from 2-3 weeks. We also found that rosiglitazone alone was unable to induce adipocyte differentiation from hMSCs in vitro. However, rosiglitazone appears to enhance hMSC adipogenesis in the presence of other hormones and/or compounds, such as DIM. Furthermore, the inhibitory activity of TGF-{beta}1 on adipogenesis could be investigated using DIMRo-treated hMSCs. We conclude that our rapid new culture method is very useful in measuring the effect of molecules that affect adipogenesis in hMSCs.

  6. New, fast corroding high ductility Mg-Bi-Ca and Mg-Bi-Si alloys, with no clinically observable gas formation in bone implants

    Energy Technology Data Exchange (ETDEWEB)

    Remennik, S., E-mail: saggym@gmail.com [Department of Materials Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Bartsch, I.; Willbold, E.; Witte, F. [Laboratory for Biomechanics and Biomaterials, Orthopaedic Clinic, Hannover Medical School, Anna-von-Borries-Str. 1-7, 30625 Hannover (Germany); Shechtman, D. [Department of Materials Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); MSE, Iowa State University, Ames, Iowa 50011 (United States)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Biodegradable, biocompatible and highly ductile Mg alloys based on the Mg-Bi system have been produced by rapid solidification and extrusion processes. Black-Right-Pointing-Pointer The implants corroded fast within the first 4 weeks after implantation in rabbit bone, but no gas formation has been clinically observed. Black-Right-Pointing-Pointer The corrosion rate could be significantly reduced in vitro and in vivo by using high purity magnesium for the alloy production. - Abstract: Current approaches to initial corrosion rate reduction of biodegradable magnesium alloys include alloying with rare earth elements, mechanical processing, coatings and the use of metallic glasses. The latter has limited ductility needed for implant adaptively to various surgery procedures. Furthermore, slow corroding magnesium alloys, coatings or metallic glasses have not proved to be fully dissolvable in vivo. With this in mind, we have developed a new class of biocompatible, biodegradable ductile magnesium alloys with 40% elongation at room temperature. The alloys are based on the Mg-Bi system and undergo a series of production routes, which include rapid solidification (RS) and various extrusion processes. The Mg-Bi-Si (B-BS) system exhibited a high corrosion rates in vitro and was excluded from in vivo screening. In preliminary experiments of Mg-Bi-Ca (B-BX) in rabbit femur bones, the alloy corroded rapidly without any clinically visible gas formation. Only 30% of the B-BX implant remained uncorroded after 4 weeks of implantation. After using low iron Mg for implant preparation the corrosion rate of HP-B-BX was reduced in bone leaving 70% of the implant uncorroded after 4 weeks, while the corrosion in intramuscular and subcutaneous sites were still high leaving only 40% and 10% uncorroded after 4 weeks. The foreign body reaction was very mild and enhanced bone formation could be observed in the vicinity of the corroding implant. Thus, these

  7. Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo

    Science.gov (United States)

    Sutha, Ken; Schwartz, Zvi; Wang, Yun; Hyzy, Sharon; Boyan, Barbara D.; McDevitt, Todd C.

    2015-01-01

    The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material (EBM) was compared to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM derived from EBs differentiated for 10 days with osteogenic media (+β-glycerophosphate) exhibited similar osteoinductivity to active DBM (osteoinduction score = 2.50 ± 0.27 vs. 2.75 ± 0.16) based on histological scoring, and exceeded inactive DBM (1.13 ± 0.13, p osteoinductivity of EBM demonstrates that morphogenic factors expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized material capable of stimulating de novo bone formation in vivo. PMID:25961152

  8. Noninvasive in vivo EPR monitoring of the methyl methacrylate polymerization during the bone cement formation.

    Science.gov (United States)

    Gallez, Bernard; Beghein, Nelson

    2002-12-01

    The curing of poly(methyl methacrylate) (PMMA) bone cement is done by a free radical polymerization. As the amount of free radicals present is a marker of the amount of unpolymerized chains present in the polymer, it is assumed that this could be related to the mechanical properties such as strength or density. In this study, the direct observation of the free radicals produced during the PMMA bone cement formation was obtained for the first time in vivo using low-frequency EPR spectrometers (1.2 GHz). Low frequency permits measurements in live animals due to the increased microwave penetration. The amount of polymerization radicals was carried out noninvasively over days on the same animals. The decay rates obtained in vitro and in vivo were compared: the decay rates were significantly lower when the curing process occurred in vivo compared to the situation in vitro. As the kinetics are rather different in vitro and in vivo, this emphasizes the value of the present method that permits the noninvasive monitoring of the curing process directly in vivo. Copyright 2002 Elsevier Science Ltd.

  9. The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells.

    Science.gov (United States)

    Bolander, J; Ji, W; Geris, L; Bloemen, V; Chai, Y C; Schrooten, J; Luyten, F P

    2016-01-05

    When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds, in vivo bone formation can be achieved. This process is dependent on the early activation of Bone morphogenetic protein (BMP)-signalling. However, the bone forming process is slow and routinely only a limited amount of bone and bone marrow is formed. Therefore, we hypothesised that a robust clinically relevant outcome could be achieved by adding more physiological levels of potent BMP-ligands to these cell- and CaP-based constructs. For this, hPDCs were characterised for their responsiveness to BMP-ligands upon in vitro 2D stimulation. BMP-2, -4, -6 and -9 robustly induced osteochondrogenic differentiation. Subsequently, these ligands were coated onto clinically approved CaP-scaffolds, BioOss® and CopiOs®, followed by hPDC-seeding. Protein lysates and conditioned media were investigated for activation of BMP signalling pathways. Upon in vivo implantation, the most abundant bone formation was found in BMP-2 and BMP-6-coated scaffolds. Implanted cells actively contributed to the newly formed bone. Remnants of cartilage could be observed in BMP-coated CopiOs®-constructs. Computational analysis displayed that the type of BMP-ligand as well as the CaP-scaffold affects skeletal tissue formation, observed in a qualitative as well as quantitative manner. Furthermore, the in vitro mechanism appears to predict the in vivo outcome. This study presents further evidence for the potential of BMP-technology in the development of clinically relevant cell-based constructs for bone regenerative strategies.

  10. Pleomorphic adenoma of parotid gland with extensive bone formation – A rare case report

    Directory of Open Access Journals (Sweden)

    Ashwin Ashok Jaiswal

    2014-07-01

    Full Text Available Pleomorphic adenoma is the most common type of all salivary gland tumors, involving more frequently the parotid gland. In most series, it represents 45–75% of all salivary gland neoplasms. We report an unusual case of a huge tumor that measured 9 × 8 cm & 400 g by weight with extensive bone formation, occurring in the parotid gland of a 22 year old man. Thorough clinical examination was done. FNAC was done which showed Myxochondroid matrix with glandular epithelial cells suggesting pleomorphic adenoma. CT scan head & neck revealed a large mass with nodular areas of calcification within soft tissue with marked narrowing of orophayngeal lumen. Total parotidectomy with preservation of facial nerve was done by the Transcervical Transparotid approach. The histopathological findings suggested the possibility of extensive endochondral ossification in pleomorphic adenoma. Preservation of facial nerve functions is a key to successful parotid surgery.

  11. Bone formation within the vicinity of biodegradable magnesium alloy implant in a rat femur model

    Science.gov (United States)

    Han, Hyung-Seop; Kim, Young-Yul; Kim, Yu-Chan; Cho, Sung-Youn; Cha, Pil-Ryung; Seok, Hyun-Kwang; Yang, Seok-Jo

    2012-04-01

    The purposes of this preliminary study were to investigate the effect of increased Ca contents (5-10 wt% Ca) in Mg-Ca alloy on the mechanical properties and osseous healing rate in a standard rat defect model. Mechanical tests were performed using a compression system followed by qualitative histological analysis using the hemotoxylin and eosin (H&E) staining method and quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase PCR). Mg-Ca alloy degraded fast in vivo while displaying a high level of the bone formation markersOC and ALP. Favorablemechanical strength properties were displayed as Ca content increased from 5 wt% to 10 wt% to show its potential to be considered as a load bearing implant material. The resultfrom this study suggests that the developed Mg-Ca alloy has the potential to serve as a biocompatible load bearing implant material that is degradable and possibly osteoconductive.

  12. Tomographic Assessment of Bone Formation After the Collares Technique of Gingivoperiosteoplasty in Patients With Cleft Lip and Palate.

    Science.gov (United States)

    Tovo, Aline H S; Prietsch, José R; Collares, Marcus V M

    2016-01-01

    This cross-sectional study sought to assess bone formation and spontaneous tooth eruption in a cohort of 25 consecutive patients aged 6 to 11 years who underwent primary gingivoperiosteoplasty by the Collares technique. Cross-sectional study assessing bone formation in the cleft area using a within-group time series design. Hospital de Clínicas de Porto Alegre (HCPA), a tertiary hospital in Brazil. Twenty-five patients with nonsyndromic, complete unilateral cleft lip and palate, no comorbidities, and unerupted permanent canines. Cheiloplasty was performed by means of the Millard II technique, with the addition of a triangle at the mucocutaneous junction, vomer flap nasal floor closure, and wide subperiosteal elevation, followed by gingivoperiosteoplasty by the Collares technique. Cone-beam computed tomography was used to assess treatment effect. In a novel method, software was used to obtain two three-dimensional reconstructions, one each of the cleft and noncleft sides, enabling quantitative comparison of bone presence in the alveolar defect area. Of the 25 patients, 24 achieved bone bridge formation. The cleft side had 75.1% (67.9%-82.3%) of the bone volume, 70.5% (53.1%-87.9%) of the height, and 63.3% (44.1%-82.5%) of the width of the noncleft side. Bone formation was 17.28% lower in patients with lateral incisor agenesis. Collares gingivoperiosteoplasty performed well as a technique for alveolar repair in patients with cleft lip and palate, allowing spontaneous eruption of deciduous and permanent lateral incisors through the bone bridge created.

  13. Fabrication of a two-level tumor bone repair biomaterial based on a rapid prototyping technique

    Energy Technology Data Exchange (ETDEWEB)

    Kai He; Yan Yongnian; Zhang Renji; Wang Xiaohong [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Wang Xinluan; Madhukar, Kumta Shekhar; Qin Ling [Department of Orthoapedics and Traumatology, The Chinese University of Hong Kong. Shatin, NT (Hong Kong)], E-mail: wangxiaohong@tsinghua.edu.cn, E-mail: kumta@cuhk.edu.hk, E-mail: qin@ort.cuhk.edu.hk

    2009-06-01

    After the removal of the giant cell tumor (GCT) of bone, it is necessary to fill the defects with adequate biomaterials. A new functional bone repair material with both stimulating osteoblast growth and inhibiting osteoclast activity has been developed with phosphorylated chitosan (P-chitosan) and disodium (1 {yields} 4)-2-deoxy-2-sulfoamino-{beta}-D-glucopyranuronan (S-chitosan) as the additives of poly(lactic acid-co-glycolic acid) (PLGA)/calcium phosphate (TCP) scaffolds based on a double-nozzle low-temperature deposition manufacturing technique. A computer-assisted design model was used and the optimal fabrication parameters were determined through the manipulation of a pure PLGA/TCP system. The microscopic structures, water absorbability and mechanical properties of the samples with different P-chitosan and S-chitosan concentrations were characterized correspondingly. The results suggested that this unique composite porous scaffold material is a potential candidate for the repair of large bone defects after a surgical removal of GCT.

  14. The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors

    Directory of Open Access Journals (Sweden)

    Lucia D’Amico

    2015-01-01

    Full Text Available Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporting the vicious cycle of bone metastasis. This review summarizes the current knowledge on the interactions among bone, immune, and tumor cells aiming to provide an overview of the osteoimmunology field in bone metastasis from solid tumors.

  15. Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model

    National Research Council Canada - National Science Library

    Liu, Chufeng; Cao, Yang; Liu, Conghua; Zhang, Jincai; Xu, Pingping

    2011-01-01

    The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time...

  16. Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.

    Science.gov (United States)

    Oxlund, H; Andersen, N B; Ortoft, G; Orskov, H; Andreassen, T T

    1998-04-01

    The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

  17. A symbiotic scenario for the rapid formation of supermassive black holes

    Science.gov (United States)

    Richter, M. C.; Tupper, G. B.; Viollier, R. D.

    2006-12-01

    The most massive black holes, lurking at the centres of large galaxies, must have formed less than a billion years after the big bang, as they are visible today in the form of bright quasars at redshift larger than six. Their early appearance is mysterious, because the radiation pressure, generated by infalling ionized matter, inhibits the rapid growth of these black holes from stellar-mass black holes. It is shown that the supermassive black holes may form timeously through the accretion of predominantly degenerate sterile neutrino dark matter onto stellar-mass black holes. Our symbiotic scenario relies on the formation of, first, supermassive degenerate sterile neutrino balls through gravitational cooling and, then, stellar-mass black holes through supernova explosions of massive stars at the centre of the neutrino balls. The observed lower and upper limits of the supermassive black holes are explained by the corresponding mass limits of the preformed neutrino balls.

  18. Immunological Reaction in TNF-α-Mediated Osteoclast Formation and Bone Resorption In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Hideki Kitaura

    2013-01-01

    Full Text Available Tumor necrosis factor-α (TNF-α is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-α may play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-κB ligand (RANKL to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-α on bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF-α is considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL- 12, IL-18, and interferon-γ (IFN-γ strongly inhibit osteoclast formation. IL-12, IL-18, and IFN-γ induce apoptosis in bone marrow cells treated with TNF-α  in vitro, and osteoclastogenesis is inhibited by the interactions of TNF-α-induced Fas and Fas ligand induced by IL-12, IL-18, and IFN-γ. This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF-α-mediated osteoclastogenesis in vitro and in vivo.

  19. Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

    Directory of Open Access Journals (Sweden)

    Ghanaati Shahram

    2013-01-01

    Full Text Available Abstract Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (β-TCP or an hydroxyapatite/silicon dioxide (HA/SiO2-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.

  20. Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone implant contact formation

    Science.gov (United States)

    Strnad, Jakub; Strnad, Zdeněk; Šesták, Jaroslav; Urban, Karel; Povýšil, Ctibor

    2007-05-01

    This study was carried out to quantify the effect of an alkali-modified surface on the bone implant interface formation during healing using an animal model. A total of 24 screw-shaped, self-tapping, (c.p.) titanium dental implants, divided into test group B—implants with alkali-modified surface (Bio surface) and control group M—implants with turned, machined surface, were inserted without pre-tapping in the tibiae of three beagle dogs. The animals were sacrificed after 2, 5 and 12 weeks and the bone implant contact (BIC%) was evaluated histometrically. The surface characteristics that differed between the implant surfaces, i.e. specific surface area, contact angle, may represent factors that influence the rate of osseointegration and the secondary implant stability. The alkali-treated surface enhances the BIC formation during the first 2 5 weeks of healing compared to the turned, machined surface.

  1. The effects of n-3 long-chain polyunsaturated fatty acids on bone formation and growth factors in adolescent boys

    DEFF Research Database (Denmark)

    Damsgaard, C. T.; Mølgaard, C.; Gyldenløve, S. N.

    2012-01-01

    with docosahexaenoic acid (DHA) status and (ii) affected by fish oil supplementation, in adolescent boys. METHODS: Seventy-eight healthy, slightly overweight 13- to 15-y-old boys were randomly assigned to breads with DHA-rich fish oil (1.1 g/d n-3 LCPUFA) or control for 16 wk. Whole-body bone mineral content (BMC......), bone area (BA), bone mineral density (BMD), plasma osteocalcin, and growth factors were measured at wk 0 and wk 16, as well as diet, physical activity, and n-3 LCPUFA status in erythrocytes. RESULTS: Fish oil strongly increased DHA status (P = 0.0001). No associations were found between DHA status...... and BMC, BA, BMD, or the markers of bone formation and growth at baseline. Furthermore, the fish oil intervention did not affect any of the outcomes as compared with control. However, dose-response analyses revealed a positive association between changes in DHA status and plasma insulin-like growth factor...

  2. Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation.

    Science.gov (United States)

    Eelen, G; Verlinden, L; Maes, C; Beullens, I; Gysemans, C; Paik, J-H; DePinho, R A; Bouillon, R; Carmeliet, G; Verstuyf, A

    2016-11-01

    The differentiation of embryonic mesenchymal cells into chondrocytes and the subsequent formation of a cartilaginous scaffold that enables the formation of long bones are hallmarks of endochondral ossification. During this process, chondrocytes undergo a remarkable sequence of events involving proliferation, differentiation, hypertrophy and eventually apoptosis. Forkhead Box O (FoxO) transcription factors (TFs) are well-known regulators of such cellular processes. Although FoxO3a was previously shown to be regulated by 1,25-dihydroxyvitamin D3 in osteoblasts, a possible role for this family of TFs in chondrocytes during endochondral ossification remains largely unstudied. By crossing Collagen2-Cre mice with FoxO1(lox/lox);FoxO3a(lox/lox);FoxO4(lox/lox) mice, we generated mice in which the three main FoxO isoforms were deleted in growth plate chondrocytes (chondrocyte triple knock-out; CTKO). Intriguingly, CTKO neonates showed a distinct elongation of the hypertrophic zone of the growth plate. CTKO mice had increased overall body and tail length at eight weeks of age and suffered from severe skeletal deformities at older ages. CTKO chondrocytes displayed decreased expression of genes involved in redox homeostasis. These observations illustrate the importance of FoxO signaling in chondrocytes during endochondral ossification. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. NGC 1266 As a local candidate for rapid cessation of star formation

    Energy Technology Data Exchange (ETDEWEB)

    Alatalo, Katherine; Graves, Genevieve; Blitz, Leo [Department of Astronomy, Hearst Field Annex, University of California, Berkeley, CA 94720 (United States); Nyland, Kristina; Young, Lisa M. [Physics Department, New Mexico Technology, Socorro, NM 87801 (United States); Deustua, Susana [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Griffin, Kristen Shapiro [Space Sciences Research Group, Northrop Grumman Aerospace Systems, Redondo Beach, CA 90278 (United States); Duc, Pierre-Alain; Bournaud, Frédéric [Laboratoire AIM Paris-Saclay, CEA/IRFU/SAp—CNRS—Université Paris Diderot, F-91191 Gif-sur-Yvette, Cedex (France); Cappellari, Michele; Bayet, Estelle; Bureau, Martin; Davies, Roger L. [Sub-Department of Astrophysics, Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH (United Kingdom); McDermid, Richard M. [Australian Astronomical Observatory, P.O. Box 296, Epping, NSW 1710 (Australia); Davis, Timothy A. [European Southern Observatory, Karl-Schwarzschild-Street 2, D-85748 Garching (Germany); Crocker, Alison F. [Department of Physics and Astronomy, University of Toledo, Toledo, OH 43606 (United States); Chang, Philip [Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, WI 53201 (United States); Scott, Nicholas [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, P.O. Box 218, Hawthorn VIC 3122 (Australia); Cales, Sabrina L. [Department of Astronomy, Faculty of Physical and Mathematical Sciences, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Bois, Maxime [Observatoire de Paris, LERMA and CNRS, 61 Avenue de l' Observatoire, F-75014 Paris (France); and others

    2014-01-10

    We present new Spectrographic Areal Unit for Research on Optical Nebulae (SAURON) integral-field spectroscopy and Swift Ultraviolet Optical Telescope (UVOT) observations of molecular outflow host galaxy NGC 1266 that indicate NGC 1266 has experienced a rapid cessation of star formation. Both the SAURON maps of stellar population age and the Swift UVOT observations demonstrate the presence of young (<1 Gyr) stellar populations within the central 1 kpc, while existing Combined Array for Research in Millimeter-Wave Astronomy CO(1-0) maps indicate that the sites of current star formation are constrained to only the inner few hundred parsecs of the galaxy. The optical spectrum of NGC 1266 from Moustakas and Kennicutt reveal a characteristic poststarburst (K+A) stellar population, and Davis et al. confirm that ionized gas emission in the system originate from a shock. Galaxies with K+A spectra and shock-like ionized gas line ratios may comprise an important, overlooked segment of the poststarburst population, containing exactly those objects in which the active galactic nucleus (AGN) is actively expelling the star-forming material. While AGN activity is not the likely driver of the poststarburst event that occurred 500 Myr ago, the faint spiral structure seen in the Hubble Space Telescope Wide-field Camera 3 Y-, J- and H-band imaging seems to point to the possibility of gravitational torques being the culprit. If the molecular gas were driven into the center at the same time as the larger scale galaxy disk underwent quenching, the AGN might be able to sustain the presence of molecular gas for ≳ 1 Gyr by cyclically injecting turbulent energy into the dense molecular gas via a radio jet, inhibiting star formation.

  4. Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Marietta Herrmann

    2018-02-01

    Full Text Available Bone is an organ with high natural regenerative capacity and most fractures heal spontaneously when appropriate fracture fixation is provided. However, additional treatment is required for patients with large segmental defects exceeding the endogenous healing potential and for patients suffering from fracture non-unions. These cases are often associated with insufficient vascularization. Transplantation of CD34+ endothelial progenitor cells (EPCs has been successfully applied to promote neovascularization of bone defects, however including extensive ex vivo manipulation of cells. Here, we hypothesized, that treatment with granulocyte colony-stimulating factor (G-CSF may improve bone healing by mobilization of CD34+ progenitor cells into the circulation, which in turn may facilitate vascularization at the defect site. In this pilot study, we aimed to characterize the different cell populations mobilized by G-CSF and investigate the influence of cell mobilization on the healing of a critical size femoral defect in rats. Cell mobilization was investigated by flow cytometry at different time points after five consecutive daily G-CSF injections. In a pilot study, bone healing of a 4.5-mm critical femoral defect in F344 rats was compared between a saline-treated control group and a G-CSF treatment group. In vivo microcomputed tomography and histology were applied to compare bone formation in both treatment groups. Our data revealed that leukocyte counts show a peak increase at the first day after the last G-CSF injection. In addition, we found that CD34+ progenitor cells, including EPCs, were significantly enriched at day 1, and further increased at day 5 and day 11. Upregulation of monocytes, granulocytes and macrophages peaked at day 1. G-CSF treatment significantly increased bone volume and bone density in the defect, which was confirmed by histology. Our data show that different cell populations are mobilized by G-CSF treatment in cell specific

  5. Optimising combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice

    DEFF Research Database (Denmark)

    Dreyer, Chris Halling; Kjærgaard, Kristian; Ditzel, Nicholas

    2017-01-01

    combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. METHODS: Twenty-eight SCID (NOD.CB17-Prkdcscid /J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1...

  6. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zaher, Walid; Larsen, Kenneth H

    2015-01-01

    INTRODUCTION: There is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues...... vivo transwell migration and following intravenous injection, better in vivo homing ability to bone fracture when compared to LBF clones. Comparative microarray analysis of HBF versus LBF clones identified enrichment of gene categories of chemo-attraction, adhesion and migration associated genes. Among...

  7. Enhanced osteoblastic differentiation and bone formation in co-culture of human bone marrow mesenchymal stromal cells and peripheral blood mononuclear cells with exogenous VEGF.

    Science.gov (United States)

    Joensuu, K; Uusitalo, L; Alm, J J; Aro, H T; Hentunen, T A; Heino, T J

    2015-05-01

    Despite recent advances in bone tissue engineering, efficient bone formation and vascularization remains a challenge for clinical applications. The aim of this study was to investigate if the osteoblastic differentiation of human mesenchymal stromal cells (MSCs) can be enhanced by co-culturing them with peripheral blood (PB) mononuclear cells (MNCs), with and without vascular endothelial growth factor (VEGF), a coupling factor of bone formation and angiogenesis. Human bone marrow (BM) derived MSCs were co-cultured with PB-MNCs in osteogenic medium with or without VEGF. Osteoblastic differentiation and mineral deposition were studied by staining for alkaline phosphatase (ALP), and von Kossa, respectively, and measurements for ALP activity and calcium concentration (Ca). Cell proliferation was assayed with Alamar blue. The mechanism(s) were further studied by Transwell(®) cell culture experiments. Both ALP and mineralization (von Kossa and Ca) were significantly higher in the MSC-MNC co-cultures compared to plain MSC cultures. VEGF alone had no effect on osteoblastic differentiation of MSCs, but further enhanced differentiation in co-culture settings. The mechanism was shown to require cell-cell contact between MSCs and MNCs and the factors contributing to further differentiation appear to be soluble. No differences were observed in cell proliferation. Our study demonstrates that the in vitro ALP activity and mineralization of human BM-MSCs is more efficient in the presence of PB-MNCs, and exogenously added VEGF further enhances the stimulatory effect. This indicates that PB-MNCs could be a potential cell source in development of co-culture systems for novel tissue engineering applications for enhanced bone healing. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Ectopic bone formation cannot occur by hydroxyapatite/{beta}-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Lijia [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Duan Xin [Department of Orthopaedics, Chengdu Second People' s Hospital, Chengdu (China); Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu (China); Xiang Zhou [Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu (China); Shi Yujun; Lu Xiaofeng; Ye Feng [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Bu Hong, E-mail: hongbu@scu.edu.cn [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Department of Pathology, West China Hospital, Sichuan University, Chengdu (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Firstly, chimeric mouse model could be established successfully by bone marrow transplantation after irradiation. Black-Right-Pointing-Pointer Secondly, bone induction can occur in wild-type mice 90 days after implantation, but not occur in chimeric mice. Black-Right-Pointing-Pointer Thirdly, destruction of immune function will block osteoinduction by calcium phosphate ceramics. - Abstract: Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/{beta}-tricalcium phosphate (HA/{beta}-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/{beta}-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede

  9. Effect of polygonimitin C on bone formation and resorption in human ...

    African Journals Online (AJOL)

    Polygonaceae), also named as Polygoni multiflori Radix, have protective effects against OP [8-10]. It has been reported that stilbene glucoside, the main active ingredient of Polygoni multiflori Radix, increased bone mineral density and bone strength in ...

  10. Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats.

    Science.gov (United States)

    Srinivasan, Kritika; Naula, Diana P; Mijares, Dindo Q; Janal, Malvin N; LeGeros, Racquel Z; Zhang, Yu

    2016-07-01

    Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-computed tomography (µCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1622-1632, 2016. © 2016 Wiley Periodicals, Inc.

  11. Muramyl Dipeptide Enhances Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption through Increased RANKL Expression in Stromal Cells

    Directory of Open Access Journals (Sweden)

    Masahiko Ishida

    2015-01-01

    Full Text Available Lipopolysaccharide (LPS is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP, the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b, and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-κB ligand (RANKL expression and Toll-like receptor 4 (TLR4 expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases.

  12. Scaffolds for bone tissue engineering fabricated from two different materials by the rapid prototyping technique: PCL versus PLGA.

    Science.gov (United States)

    Park, So Hee; Park, Dae Sung; Shin, Ji Won; Kang, Yun Gyeong; Kim, Hyung Keun; Yoon, Taek Rim; Shin, Jung-Woog

    2012-11-01

    Three dimensional tissue engineered scaffolds for the treatment of critical defect have been usually fabricated by salt leaching or gas forming technique. However, it is not easy for cells to penetrate the scaffolds due to the poor interconnectivity of pores. To overcome these current limitations we utilized a rapid prototyping (RP) technique for fabricating tissue engineered scaffolds to treat critical defects. The RP technique resulted in the uniform distribution and systematic connection of pores, which enabled cells to penetrate the scaffold. Two kinds of materials were used. They were poly(ε-caprolactone) (PCL) and poly(D, L-lactic-glycolic acid) (PLGA), where PCL is known to have longer degradation time than PLGA. In vitro tests supported the biocompatibility of the scaffolds. A 12-week animal study involving various examinations of rabbit tibias such as micro-CT and staining showed that both PCL and PLGA resulted in successful bone regeneration. As expected, PLGA degraded faster than PCL, and consequently the tissues generated in the PLGA group were less dense than those in the PCL group. We concluded that slower degradation is preferable in bone tissue engineering, especially when treating critical defects, as mechanical support is needed until full regeneration has occurred.

  13. Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration.

    Science.gov (United States)

    Martínez-Vázquez, F J; Cabañas, M V; Paris, J L; Lozano, D; Vallet-Regí, M

    2015-03-01

    Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry before the extrusion of the structures. The release profile of this antibiotic was measured in phosphate-buffered saline solution by high-performance liquid chromatography and was adjusted to a first-order release kinetics. Vancomycin released from the material was also shown to inhibit bacterial growth in vitro. The implications of these results for bone tissue engineering applications are discussed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    Energy Technology Data Exchange (ETDEWEB)

    Vani, R; Sridevi, T S; Kalkura, S Narayana [Crystal Growth Centre, Anna University, Chennai 600 025 (India); Raja, Subramaniya Bharathi; Savithri, K; Devaraj, S Niranjali [Department of Biochemistry, University of Madras, Chennai 600 025 (India); Girija, E K [Department of Physics, Periyar University, Salem 636 011 (India); Thamizhavel, A, E-mail: kalkurasn@annauniv.edu, E-mail: kalkura@yahoo.com [Tata Institute of Fundamental Research, Mumbai 400005 (India)

    2011-07-15

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m{sup 2} g{sup -1} and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  15. Balancing the rates of new bone formation and polymer degradation enhances healing of weight-bearing allograft/polyurethane composites in rabbit femoral defects.

    Science.gov (United States)

    Dumas, Jerald E; Prieto, Edna M; Zienkiewicz, Katarzyna J; Guda, Teja; Wenke, Joseph C; Bible, Jesse; Holt, Ginger E; Guelcher, Scott A

    2014-01-01

    There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling.

  16. Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

    Directory of Open Access Journals (Sweden)

    Jin Wook Hwang

    2016-01-01

    Full Text Available Absorbable extracellular matrix (ECM membrane has recently been used as a barrier membrane (BM in guided tissue regeneration (GTR and guided bone regeneration (GBR. Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18–0.35 mm but with excellent mechanical properties. Tensile strength of APP was 14.15±2.24 MPa. In in vivo experiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months.

  17. Can Spatiotemporal Fluoride (18F-) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET/CT.

    Science.gov (United States)

    Lundblad, Henrik; Karlsson-Thur, Charlotte; Maguire, Gerald Q; Jonsson, Cathrine; Noz, Marilyn E; Zeleznik, Michael P; Weidenhielm, Lars

    2017-05-01

    When a bone is broken for any reason, it is important for the orthopaedic surgeon to know how bone healing is progressing. There has been resurgence in the use of the fluoride (18F-) ion to evaluate various bone conditions. This has been made possible by availability of positron emission tomography (PET)/CT hybrid scanners together with cyclotrons. Absorbed on the bone surface from blood flow, 18F- attaches to the osteoblasts in cancellous bone and acts as a pharmacokinetic agent, which reflects the local physiologic activity of bone. This is important because it shows bone formation indicating that the bone is healing or no bone formation indicating no healing. As 18F- is extracted from blood in proportion to blood flow and bone formation, it thus enables determination of bone healing progress. The primary objective of this study was to determine whether videos showing the spatiotemporal uptake of 18F- via PET bone scans could show problematic bone healing in patients with complex tibia conditions. A secondary objective was to determine if semiquantification of radionuclide uptake was consistent with bone healing. This study investigated measurements of tibia bone formation in patients with complex fractures, osteomyelitis, and osteotomies treated with a Taylor Spatial FrameTM (TSF) by comparing clinical healing progress with spatiotemporal fluoride (18F-) uptake and the semiquantitative standardized uptake value (SUV). This procedure included static and dynamic image acquisition. For intrapatient volumes acquired at different times, the CT and PET data were spatially registered to bring the ends of the bones that were supposed to heal into alignment. To qualitatively observe how and where bone formation was occurring, time-sequenced volumes were reconstructed and viewed as a video. To semiquantify the uptake, the mean and maximum SUVs (SUVmean, SUVmax) were calculated for the ends of the bones that were supposed to heal and for normal bone, using a spherical

  18. Suppression of EZH2 Prevents the Shift of Osteoporotic MSC Fate to Adipocyte and Enhances Bone Formation During Osteoporosis.

    Science.gov (United States)

    Jing, Huan; Liao, Li; An, Yulin; Su, Xiaoxia; Liu, Shiyu; Shuai, Yi; Zhang, Xinjing; Jin, Yan

    2016-02-01

    During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment. However, whether EZH2 is related to osteoporosis remains elusive. In our study, we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2 directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to silence Wnt gene transcription. The inhibition of Wnt/β-catenin signaling shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus-expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo administration of DZNep successfully increased bone formation and repressed excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage commitment to adipocyte, which contributed to the development of osteoporosis. We also provided EZH2 as a novel therapeutic target for improving bone formation during osteoporosis.

  19. Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation.

    Science.gov (United States)

    Cho, Hyeong-jin; Perikamana, Sajeesh Kumar Madhurakkat; Lee, Ji-hye; Lee, Jinkyu; Lee, Kyung-Mi; Shin, Choongsoo S; Shin, Heungsoo

    2014-07-23

    Although bone morphogenic proteins (BMPs) have been widely used for bone regeneration, the ideal delivery system with optimized dose and minimized side effects is still active area of research. In this study, we developed bone morphogenetic protein-2(BMP-2) immobilized poly(l-lactide) (PLLA) nanofibers inspired by polydopamine, which could be ultimately used as membranes for guided bone regeneration, and investigated their effect on guidance of in vitro cell behavior and in vivo bone formation. Surface chemical analysis of the nanofibers confirmed successful immobilization of BMP-2 mediated by polydopamine, and about 90% of BMP-2 was stably retained on the nanofiber surface for at least 28 days. The alkaline phosphatase activity and calcium mineralization of human mesenchymal stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively small dose was highly active following implantation to the critical-sized defect in the cranium of mice; radiographic analysis demonstrated that 77.8 ± 11.7% of newly formed bone was filled within the defect for a BMP-2-immobilized groups at the concentration of 124 ± 9 ng/cm(2), as compared to 5.9 ± 1.0 and 34.1 ± 5.5% recovery, for a defect-only and a polydopamine-only group, respectively. Scanning and transmission electron microscopy of samples from the BMP-2 immobilized group showed fibroblasts and osteoblasts with nanofiber strands in the middle of regenerated bone tissue, revealing the importance of interaction between implanted nanofibers and the neighboring extracellular environment. Taken together, our data support that the presentation of BMP-2 on the surface of nanofibers as immobilized by utilizing polydopamine chemistry may be an effective method to direct bone growth at relatively low local concentration.

  20. Rapid Formation of Black Holes in Galaxies: A Self-limiting Growth Mechanism

    Science.gov (United States)

    Li, Zhi; Sellwood, J. A.; Shen, Juntai

    2017-11-01

    We present high-quality fluid dynamical simulations of isothermal gas flows in a rotating barred potential. We show that a large quantity of gas is driven right into the nucleus of a galaxy when the model lacks a central mass concentration, but the inflow stalls at a nuclear ring in comparison simulations that include a central massive object. The radius of the nuclear gas ring increases linearly with the mass of the central object. We argue that bars drive gas right into the nucleus in the early stages of disk galaxy formation, where a nuclear star cluster and perhaps a massive black hole could be created. The process is self-limiting, however, because inflow stalls at a nuclear ring once the mass of gas and stars in the nucleus exceeds ˜1% of the disk mass, which shuts off rapid growth of the black hole. We briefly discuss the relevance of these results to the seeding of massive black holes in galaxies, the merger model for quasar evolution, and the existence of massive black holes in disk galaxies that lack a significant classical bulge.

  1. The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    Science.gov (United States)

    Ripamonti, U; Richter, P W; Nilen, R W N; Renton, L

    2008-01-01

    Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/β-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-β superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response. PMID:18363843

  2. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow

    Science.gov (United States)

    Colter, David C.; Class, Reiner; DiGirolamo, Carla M.; Prockop, Darwin J.

    2000-01-01

    Cultures of plastic-adherent cells from bone marrow have attracted interest because of their ability to support growth of hematopoietic stem cells, their multipotentiality for differentiation, and their possible use for cell and gene therapy. Here we found that the cells grew most rapidly when they were initially plated at low densities (1.5 or 3.0 cells/cm2) to generate single-cell derived colonies. The cultures displayed a lag phase of about 5 days, a log phase of rapid growth of about 5 days, and then a stationary phase. FACS analysis demonstrated that stationary cultures contained a major population of large and moderately granular cells and a minor population of small and agranular cells here referred to as recycling stem cells or RS-1 cells. During the lag phase, the RS-1 cells gave rise to a new population of small and densely granular cells (RS-2 cells). During the late log phase, the RS-2 cells decreased in number and regenerated the pool of RS-1 cells found in stationary cultures. In repeated passages in which the cells were plated at low density, they were amplified about 109-fold in 6 wk. The cells retained their ability to generate single-cell derived colonies and therefore apparently retained their multipotentiality for differentiation. PMID:10725391

  3. Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

    Science.gov (United States)

    2014-10-03

    Percutaneous vertebroplasty and kyphoplasty for the stand alone augmentation of osteoporosis induced ver tebral compression fractures: present status... induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6...formation and induced approximately zero-order degradation of the polymer. The consequent bal- ance of new bone formation and polymer degradation re- sulted

  4. Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

    DEFF Research Database (Denmark)

    Jensen, Simon S; Chen, B; Bornstein, Michael M

    2011-01-01

    Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole...... or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major...... challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed....

  5. Biphasic β-TCP mixed with silicon increases bone formation in critical site defects in rabbit calvaria.

    Science.gov (United States)

    Calvo-Guirado, José Luis; Garces, Miguel; Delgado-Ruiz, Rafael Arcesio; Ramirez Fernandez, Maria P; Ferres-Amat, Eduard; Romanos, Georgios E

    2015-08-01

    The aim of this study was to assess the bone regeneration of critical size defects in rabbit calvarias filled with β-TCP doped with silicon. Twenty-one New Zealand rabbits were used in this study. Two critical size defects were created in the parietal bones. Three experimental groups were evaluated: Test A (HA/β-TCP granules alone), Test B (HA/β-TCP granules plus 3% silicon), Control (empty defect). The animals were sacrificed at 8 and 12 weeks. Evaluation was performed by μCT analysis and histomorphometry. μCT evaluation showed higher volume reduction in Test A group compared with Test B (P TCP plus 3% silicon increases bone formation in critical size defects in rabbit calvarias, and the incorporation of 3% silicon reduces the resorption rate of the HA/β-TCP granules. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model.

    Directory of Open Access Journals (Sweden)

    Chufeng Liu

    Full Text Available OBJECTIVE: The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time. METHOD: Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression. RESULTS: The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63±0.10 mm and the average anchorage losses were 1.25±0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs. CONCLUSIONS: This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications. CLINICAL RELEVANCE: It may become a novel method to shorten the clinical orthodontic treatment time in the future.

  7. New bone formation at the site of autotransplanted developing mandibular canines: a case report.

    Science.gov (United States)

    Plakwicz, Pawel; Wojtaszek, Julita; Zadurska, Malgorzata

    2013-01-01

    Until recently, adequate bone at the recipient site has been a determinant for tooth autotransplantation. This article presents the transplantation of developing mandibular canines to a suboptimal position because of inadequate bone at the recipient sites. Five years later, after eruption and orthodontic alignment, all criteria for successful healing were fulfilled. In addition, new bone that was not present at the time of surgery was identified at the roots of the transplanted teeth, implying that transplanted developing teeth can stimulate bone to grow along their roots.

  8. Platelet lysate coating on scaffolds directly and indirectly enhances cell migration, improving bone and blood vessel formation.

    Science.gov (United States)

    Leotot, Julie; Coquelin, Laura; Bodivit, Gwellaouen; Bierling, Philippe; Hernigou, Philippe; Rouard, Helene; Chevallier, Nathalie

    2013-05-01

    Suitable colonization and vascularization of tissue-engineered constructs after transplantation represent critical steps for the success of bone repair. Human platelet lysate (hPL) is composed of numerous growth factors known for their proliferative, differentiative and chemo-attractant effects on various cells involved in wound healing and bone growth. The aim of this study was to determine whether the delivery of human mesenchymal stromal cells (hMSC) seeded on hPL-coated hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) scaffolds could enhance vascularization and bone formation, as well as to investigate the mechanisms by which hMSC participate in tissue regeneration. Our study demonstrates that hPL can be coated on HA/β-TCP scaffolds, which play direct and indirect effects on implanted and/or resident stem cells. Effectively, we show that hPL coating directly increases chemo-attraction to and adhesion of hMSC and endothelial cells on the scaffold. Moreover, we show that hPL coating induces hMSC to produce and secrete pro-angiogenic proteins (placental growth factor and vascular endothelial growth factor) which allow the proliferation and specific chemo-attraction of endothelial cells in vitro, thus improving in vivo neovascularization and new bone formation. This study highlights the potential of functionalizing biomaterials with hPL and shows that this growth factor combination can have synergistic effects leading to enhanced bone and blood vessel formation. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism.

    Science.gov (United States)

    Philbrick, Kenneth A; Wong, Carmen P; Branscum, Adam J; Turner, Russell T; Iwaniec, Urszula T

    2017-03-01

    Leptin, the protein product of the ob gene, is essential for normal bone growth, maturation and turnover. Peripheral actions of leptin occur at lower serum levels of the hormone than central actions because entry of leptin into the central nervous system (CNS) is limited due to its saturable transport across the blood-brain barrier (BBB). We performed a study in mice to model the impact of leptin production associated with different levels of adiposity on bone formation and compared the response with well-established centrally mediated actions of the hormone on energy metabolism. Leptin was infused (0, 4, 12, 40, 140 or 400 ng/h) for 12 days into 6-week-old female ob/ob mice (n = 8/group) using sc-implanted osmotic pumps. Treatment resulted in a dose-associated increase in serum leptin. Bone formation parameters were increased at EC50 infusion rates of 7-17 ng/h, whereas higher levels (EC50, 40-80 ng/h) were required to similarly influence indices of energy metabolism. We then analyzed gene expression in tibia and hypothalamus at dose rates of 0, 12 and 140 ng/h; the latter dose resulted in serum leptin levels similar to WT mice. Infusion with 12 ng/h leptin increased the expression of genes associated with Jak/Stat signaling and bone formation in tibia with minimal effect on Jak/Stat signaling and neurotransmitters in hypothalamus. The results suggest that leptin acts peripherally to couple bone acquisition to energy availability and that limited transport across the BBB insures that the growth-promoting actions of peripheral leptin are not curtailed by the hormone's CNS-mediated anorexigenic actions. © 2017 Society for Endocrinology.

  10. Rapid Formation of Molecular Bromine from Deliquesced NaBr Aerosol in the Presence of Ozone and UV Light

    Science.gov (United States)

    The formation of gas-phase bromine from aqueous sodium bromide aerosols is investigated through a combination of chamber experiments and chemical kinetics modeling. Experiments show that Br2(g) is produced rapidly from deliquesced NaBr aerosols in the presence of OH radicals prod...

  11. Design and fabrication of standardized hydroxyapatite scaffolds with a defined macro-architecture by rapid prototyping for bone-tissue-engineering research

    NARCIS (Netherlands)

    Wilson, C.E.; Wilson, C.E.; de Bruijn, Joost Dick; van Blitterswijk, Clemens; Verbout, A.J.; Dhert, W.J.A.

    2004-01-01

    This investigation describes the production and characterization of calcium phosphate scaffolds with defined and reproducible porous macro-architectures and their preliminary in vitro and in vivo bone-tissue-engineered response. Fugitive wax molds were designed and produced using a rapid prototyping

  12. Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    Science.gov (United States)

    Cheng, Lijia; Duan, Xin; Xiang, Zhou; Shi, Yujun; Lu, Xiaofeng; Ye, Feng; Bu, Hong

    2012-12-01

    Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/β-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone induction in the future.

  13. A Novel HA/β-TCP-Collagen Composite Enhanced New Bone Formation for Dental Extraction Socket Preservation in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

    Full Text Available Past studies in humans have demonstrated horizontal and vertical bone loss after six months following tooth extraction. Many biomaterials have been developed to preserve bone volume after tooth extraction. Type I collagen serves as an excellent delivery system for growth factors and promotes angiogenesis. Calcium phosphate ceramics have also been investigated because their mineral chemistry resembles human bone. The aim of this study was to compare the performance of a novel bioresorbable purified fibrillar collagen and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP ceramic composite versus collagen alone and a bovine xenograft-collagen composite in beagles. Collagen plugs, bovine graft-collagen composite and HA/β-TCP-collagen composite were implanted into the left and right first, second and third mandibular premolars, and the fourth molar was left empty for natural healing. In total, 20 male beagle dogs were used, and quantitative and histological analyses of the extraction ridge was done. The smallest width reduction was 19.09% ± 8.81% with the HA/β-TCP-collagen composite at Week 8, accompanied by new bone formation at Weeks 4 and 8. The HA/β-TCP-collagen composite performed well, as a new osteoconductive and biomimetic composite biomaterial, for socket bone preservation after tooth extraction.

  14. Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production

    Science.gov (United States)

    Kim, Won; Bae, Seyeon; Kim, Hyemin; Kim, Yejin; Choi, Jiwon; Lim, Sun Young; Lee, Hei Jin; Lee, Jihyuk; Choi, Jiyea; Jang, Mirim; Lee, Kyoung Eun; Chung, Sun G.; Hwang, Young-il

    2013-01-01

    The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels. PMID:24386598

  15. Incorporation of raloxifene-impregnated allograft around orthopedic titanium implants impairs early fixation but improves new bone formation.

    Science.gov (United States)

    Hermansen, Lars L; Sørensen, Mette; Barckman, Jeppe; Bechtold, Joan E; Søballe, Kjeld; Baas, Jørgen

    2015-02-01

    The anti-osteoporotic drug raloxifene reduces the risk of vertebral fractures by increasing bone mass density. We investigated whether raloxifene offers any benefits in augmenting early fixation of orthopedic implants in the setting of impaction bone grafting. 24 non-weight-bearing grafted gap implants were inserted bilaterally into the tibia of 12 dogs. The 2.5-mm peri-implant gap was filled with either raloxifene-impregnated or untreated bone allograft. Implants were harvested after 28 days. Implant fixation was assessed by mechanical testing and histomorphometric evaluation. Raloxifene-treated allograft reduced early implant fixation compared to untreated allograft, as measured by inferior maximum shear strength (p raloxifene group had more newly formed bone in the gap around the implant (p = 0.02), but also less allograft (p = 0.03). The accelerated allograft resorption in the raloxifene group explained the impaired early fixation, despite its stimulation of new bone formation. Our results with local and possible high-dose treatment are not consistent with current theory regarding the mechanism of how systemic raloxifene administration counteracts the decrease in BMD in postmenopausal women. Instead of being solely anti-resorptive as generally held, our results indicate a possible anabolic side of raloxifene.

  16. Effect of acemannan, an extracted polysaccharide from Aloe vera, on BMSCs proliferation, differentiation, extracellular matrix synthesis, mineralization, and bone formation in a tooth extraction model.

    Science.gov (United States)

    Boonyagul, Sani; Banlunara, Wijit; Sangvanich, Polkit; Thunyakitpisal, Pasutha

    2014-07-01

    Aloe vera is a traditional wound healing medicine. We hypothesized acemannan, a polysaccharide extracted from Aloe vera gel, could affect bone formation. Primary rat bone marrow stromal cells (BMSCs) were treated with various concentrations of acemannan. New DNA synthesis, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein, osteopontin expression, and mineralization were determined by [(3)H] thymidine incorporation assay, ELISA, biochemical assay, western blotting, and Alizarin Red staining, respectively. In an animal study, mandibular right incisors of male Sprague-Dawley rats were extracted and an acemannan treated sponge was placed in the socket. After 1, 2, and 4 weeks, the mandibles were dissected. Bone formation was evaluated by dual-energy X-ray absorptiometry and histopathological examination. The in vitro results revealed acemannan significantly increased BMSC proliferation, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein and osteopontin expression, and mineralization. In-vivo results showed acemannan-treated groups had higher bone mineral density and faster bone healing compared with untreated controls. A substantial ingrowth of bone trabeculae was observed in acemannan-treated groups. These data suggest acemannan could function as a bioactive molecule inducing bone formation by stimulating BMSCs proliferation, differentiation into osteoblasts, and extracellular matrix synthesis. Acemannan could be a candidate natural biomaterial for bone regeneration.

  17. Gellan gum based physical hydrogels incorporating highly valuable endogen molecules and associating BMP-2 as bone formation platforms.

    Science.gov (United States)

    López-Cebral, Rita; Civantos, Ana; Ramos, Viviana; Seijo, Begoña; López-Lacomba, José Luis; Sanz-Casado, José Vicente; Sanchez, Alejandro

    2017-07-01

    Physical hydrogels have been designed for a double purpose: as growth factor delivery systems and as scaffolds to support cell colonization and formation of new bone. Specifically, the polysaccharide gellan gum and the ubiquitous endogenous molecules chondroitin, albumin and spermidine have been used as exclusive components of these hydrogels. The mild ionotropic gelation technique was used to preserve the bioactivity of the selected growth factor, rhBMP-2. In vitro tests demonstrated the effective delivery of rhBMP-2 in its bioactive form. In vivo experiments performed in the muscle tissue of Wistar rats provided a proof of concept of the ability of the developed platforms to elicit new bone formation. Furthermore, this biological effect was better than that of a commercial formulation currently used for regenerative purposes, confirming the potential of these hydrogels as new and innovative growth factor delivery platforms and scaffolds for regenerative medicine applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Does stinging nettle (Urtica dioica) have an effect on bone formation in the expanded inter-premaxillary suture?

    Science.gov (United States)

    Irgin, Celal; Çörekçi, Bayram; Ozan, Fatih; Halicioğlu, Koray; Toptaş, Orçun; Birinci Yildirim, Arzu; Türker, Arzu; Yilmaz, Fahri

    2016-09-01

    To determine whether systemically given stinging nettle (SN) has an effect on bone formation in response to expansion of the rat inter-premaxillary suture. A total of 28 male Wistar albino rats were randomly divided into 4 equal groups: control (C), only expansion (OE), SN extract given only during the expansion and retention periods (SN group; a total of 17days), and SN extract given during the nursery phase before expansion (a period of 40days) and during the expansion and retention periods (N+SN group; a total of 57days). After the 5-day expansion period was completed, the rats in the OE, SN, and N+SN groups underwent 12days of mechanical retention, after which they were sacrificed, and their premaxilla were dissected and fixed. A histologic evaluation was done to determine the number of osteoblasts, osteoclasts, and capillaries, as well as the number and intensity of inflammatory cells and new bone formation. Statistically significant differences were found between the groups in all histologic parameters except the ratio of intensities of inflammatory cells. New bone formation and the number of capillaries were significantly higher in the SN groups than in the other groups. The statistical analysis also showed that the numbers of osteoblasts, osteoclasts, and capillaries were highest in the N+SN group. Systemic administration of SN may be effective in accelerating new bone formation and reducing inflammation in the maxillary expansion procedure. It may also be beneficial in preventing relapse after the expansion procedure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Rapid bone repair in a patient with lung cancer metastases to the spine using a novel herbal medicine: A case report.

    Science.gov (United States)

    Pu, Rong; Zhao, Qianhong; Li, Zhimei; Zhang, Lingyan; Luo, Xiaolu; Zeren, Yangji; Yu, Cui; Li, Xianyong

    2016-09-01

    The prognosis of lung carcinoma with metastasis to the bone, particularly to the spine, is poor. Chemotherapy and radiotherapy are established treatments for metastatic bone disease, but their effectiveness is unsatisfactory and bone repair following their use is slow and difficult. Medicine prepared from herbal extracts may be an alternative treatment option. The present study discusses the case of a 59-year-old patient diagnosed with squamous cell lung cancer (T2N3M1) in which first-line chemotherapy using docetaxel plus cisplatin failed. Heavy multiple bone metastases were detected in the T9 vertebra and sixth left rib, resulting in a high risk of pathological fracture. Eastern Cooperative Oncology Group (ECOG) and numerical rating scale (NRS) scores of pain were 2 and 4, respectively. A second-line treatment was chosen consisting of biological intracontrol treatment (BICT) plus bisphosphonates administered over 40 days. BICT is a therapy involving the use of herbal extracts (including ginseng, herba agrimoniae, hairyvein agrimonia herb, white flower patrinia herb and arginine) and palliative care. A partial positive response was reached following use of this regimen, particularly with regard to bone repair. A computed tomography scan revealed a 90% reduction in the broken area of the rib cage and T9 vertebra. The bone repair was rapid and almost complete. In addition, growth of the primary tumor in the right pulmonary hilar and metastasis in the mediastinal lymph nodes were stabilized following treatment. ECOG and NRS scores were decreased to 1 and 0, respectively, leading to an improved quality of life. Based on these results, the present study suggests that this herbal medicine-based regimen promotes bone repair and inhibits tumor growth, with low toxicity. However, the mechanism by which herbal medicine promotes rapid bone repair is unclear. Further studies are required to determine whether cells in the tumor microenvironment are stimulated to undergo re

  20. Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

    Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

  1. Fibrous dysplasia complicated by aneurysmal bone cyst formation affecting multiple cervical vertebrae

    Energy Technology Data Exchange (ETDEWEB)

    Lomasney, L.M.; Demos, T.C. [Dept. of Radiology, Loyola Univ. Medical Center, Maywood, IL (United States); Basu, A. [Stritch School of Medicine, Chicago, IL (United States); Laskin, W. [Dept. of Pathology, Northwestern Univ. Medical Center, Chicago, IL (United States)

    2003-09-01

    Fibrous dysplasia is a well-known benign dysplastic process of bone. However, fibrous dysplasia is very uncommon in the spine. Further, to our knowledge, co-existence of fibrous dysplasia and aneurysmal bone cyst in the spine has not been reported. This manuscript presents a patient who had both processes involving the cervical spine. (orig.)

  2. Type III collagen modulates fracture callus bone formation and early remodeling

    Science.gov (United States)

    Miedel, Emily L.; Brisson, Becky K.; Hamilton, Todd; Gleason, Hadley; Swain, Gary P.; Lopas, Luke; Dopkin, Derek; Perosky, Joseph E.; Kozloff, Kenneth M.; Hankenson, Kurt D.; Volk, Susan W.

    2015-01-01

    Type III collagen (Col3) has been proposed to play a key role in tissue repair based upon its temporospatial expression during the healing process of many tissues, including bone. Given our previous finding that Col3 regulates the quality of cutaneous repair, as well as our recent data supporting its role in regulating osteoblast differentiation and trabecular bone quantity, we hypothesized that mice with diminished Col3 expression would exhibit altered long-bone fracture healing. To determine the role of Col3 in bone repair, young adult wild-type (Col3+/+) and haploinsufficent (Col3 +/−) mice underwent bilateral tibial fractures. Healing was assessed 7, 14, 21, and 28 days following fracture utilizing microcomputed tomography (microCT), immunohistochemistry and histomorphometry. MicroCT analysis revealed a small but significant increase in bone volume fraction in Col3+/− mice at day 21. However, histological analysis revealed that Col3+/− mice have less bone within the callus at days 21 and 28, which is consistent with the established role for Col3 in osteogenesis. Finally, a reduction in fracture callus osteoclastic activity in Col3+/− mice suggests Col3 also modulates callus remodeling. Although Col3 haploinsufficiency affected biological aspects of bone repair, it did not affect the regain of mechanical function in the young mice that were evaluated in this study. These findings provide evidence for a modulatory role for Col3 in fracture repair and support further investigations into its role in impaired bone healing. PMID:25626998

  3. Strontium-Containing Apatite/Poly Lactide Composites Favoring Osteogenic Differentiation and in Vivo Bone Formation

    NARCIS (Netherlands)

    Luo, Xiaoman; Barbieri, D.; Zhang, Yunfei; Yan, Yonggang; de Bruijn, Joost Dick; Yuan, Huipin

    2015-01-01

    Strontium was shown to enhance bone growth; however, its oral administration may lead to severe side effects. The application of strontium in orthopedic biomaterials may therefore be an alternative to achieve targeted and sustained strontium treatment to the surgery site in aid of bone growth

  4. Rapid oriented fibril formation of fish scale collagen facilitates early osteoblastic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Matsumoto, Rena; Uemura, Toshimasa; Xu, Zhefeng; Yamaguchi, Isamu; Ikoma, Toshiyuki; Tanaka, Junzo

    2015-08-01

    We studied the effect of fibril formation of fish scale collagen on the osteoblastic differentiation of human mesenchymal stem cells (hMSCs). We found that hMSCs adhered easily to tilapia scale collagen, which remarkably accelerated the early stage of osteoblastic differentiation in hMSCs during in vitro cell culture. Osteoblastic markers such as ALP activity, osteopontin, and bone morphogenetic protein 2 were markedly upregulated when the hMSCs were cultured on a tilapia collagen surface, especially in the early osteoblastic differentiation stage. We hypothesized that this phenomenon occurs due to specific fibril formation of tilapia collagen. Thus, we examined the time course of collagen fibril formation using high-speed atomic force microscopy. Moreover, to elucidate the effect of the orientation of fibril formation on the differentiation of hMSCs, we measured ALP activity of hMSCs cultured on two types of tilapia scale collagen membranes with different degrees of fibril formation. The ALP activity in hMSCs cultured on a fibrous collagen membrane was significantly higher than on a non-fibrous collagen membrane even before adding osteoblastic differentiation medium. These results showed that the degree of the fibril formation of tilapia collagen was essential for the osteoblastic differentiation of hMSCs. © 2014 Wiley Periodicals, Inc.

  5. Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption.

    Science.gov (United States)

    Xu, Leqin; Luo, Jian; Jin, Rongrong; Yue, Zhiying; Sun, Peng; Yang, Zhengfeng; Yang, Xinghai; Wan, Wei; Zhang, Jishen; Li, Shichang; Liu, Mingyao; Xiao, Jianru

    2016-05-01

    Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-κB signaling-related cytokines, including TNFα, MCP-1, IL1α, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-κB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC-induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC-induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell-induced bone destruction in vivo As a result, bortezomib suppressed NF-κB-regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-κB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854-65. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients...... received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also...... studied in vitro. RESULTS: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro...

  7. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

    Science.gov (United States)

    Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

  8. Influence of the cutting edge angle of a titanium instrument on chip formation in the machining of trabecular and cortical bone.

    Science.gov (United States)

    von See, Constantin; Stoetzer, Marcus; Ruecker, Martin; Wagner, Max; Schumann, Paul; Gellrich, Nils-Claudius

    2014-01-01

    The placement of self-tapping implants is associated with microfractures and the formation of bone chips along the cutting flutes. This study was conducted to investigate the effect of different cutting edge angles on chip formation during the machining of trabecular and cortical bone using instruments with a rough titanium surface. Mandibular cortical and trabecular bone specimens were obtained from freshly slaughtered domestic pigs. A predefined thrust force was applied to the specimens. Four specially designed cutting instruments that simulated dental implants and had a rough titanium surface were allowed to complete one full revolution at cutting edge angles of 55, 65, 75, and 85 degrees, respectively. Torque and thrust were measured during the cutting process. Bone chips were measured and weighed under a microscope. Different cutting edge angles did not lead to significant differences in torque. The lowest torque values were measured when the cutting edges were positioned at 65 degrees in trabecular bone and at 85 degrees in cortical bone. Bone chips were significantly larger and heavier at angles of 55 and 65 degrees than at angles of 75 and 85 degrees in trabecular bone. Instruments with a rough titanium surface show considerable angle-dependent differences in chip formation. In addition to bone density, the angle of the cutting edges should be taken into consideration during the placement of dental implants. Good results were obtained when the cutting edges were positioned at an angle of 65 degrees. This angle can have positive effects on osseointegration.

  9. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Bleil, Janine; Maier, Rene

    2016-01-01

    Background: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor kappa B ligand (RANKL) blockade on severity...

  10. Organ printing: the future of bone regeneration?

    Science.gov (United States)

    Fedorovich, Natalja E; Alblas, Jacqueline; Hennink, Wim E; Oner, F Cumhur; Dhert, Wouter J A

    2011-12-01

    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. In Vivo Static Creep Loading of the Rat Forelimb Reduces Ulnar Structural Properties at Time-Zero and Induces Damage-Dependent Woven Bone Formation

    Science.gov (United States)

    Lynch, Jennifer A.; Silva, Matthew J.

    2008-01-01

    Periosteal woven bone forms in response to stress fractures and pathological overload. The mechanical factors that regulate woven bone formation are poorly understood. Fatigue loading of the rat ulna triggers a woven bone response in proportion to the level of applied fatigue displacement. However, because fatigue produces damage by application of cyclic loading it is unclear if the osteogenic response is due to bone damage (injury response) or dynamic strain (adaptive response). Creep loading, in contrast to fatigue, involves application of a static force. Our objectives were to use static creep loading of the rat forelimb to produce discrete levels of ulnar damage, and subsequently to determine the bone response over time. We hypothesized that 1) increases in applied displacement during loading correspond to ulnae with increased crack number, length and extent, as well as decreased mechanical properties; and 2) in vivo creep loading stimulates a damage-dependent dose-response in periosteal woven bone formation. Creep loading of the rat forelimb to progressive levels of sub-fracture displacement led to progressive bone damage (cracks) and loss of whole-bone mechanical properties (especially stiffness) at time-zero. For example, loading to 60% of fracture displacement caused a 60% loss of ulnar stiffness and a 25% loss of strength. Survival experiments showed that woven bone formed in a dose-dependent manner, with greater amounts of woven bone in ulnae that were loaded to higher displacements. Furthermore, after 14 days the mechanical properties of the loaded limb were equal or superior to control, indicating functional repair of the initial damage. We conclude that bone damage created without dynamic strain triggers a woven bone response, and thus infer that the woven bone response reported after fatigue loading and in stress fractures is in large part a response to bone damage. PMID:18295561

  12. The Effects of Pioglitazone on Bone Formation and Resorption Markers in Type 2 Diabetes Mellitus

    National Research Council Canada - National Science Library

    Mori, Hiroko; Okada, Yosuke; Tanaka, Yoshiya

    2017-01-01

    ...; however, the underlying mechanism is not clear. In this prospective study, we compared the effects of pioglitazone and metformin on bone metabolism in Japanese patients with type 2 diabetes mellitus...

  13. An in vivo study on bone formation behavior of microporous granular calcium phosphate.

    Science.gov (United States)

    Dalmônico, G M L; Franczak, P F; Levandowski, N; Camargo, N H A; Dallabrida, A L; da Costa, B D; Gil, O García; Cambra-Moo, O; Rodríguez, M A; Canillas, M

    2017-06-27

    This study was developed based on in vivo investigation of microporous granular biomaterials based on calcium phosphates, involving matrices of β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), biphasic compositions of both phases and a control group. The physicochemical characterization of materials was carried out by X-Ray diffraction (DRX) and mercury porosimetry. Biodegradability, bioactivity and neoformation processes were investigated by Raman spectroscopy, scanning electron microscopy (SEM) and polarized light conducted on biopsies obtained from in vivo tests for periods of 90 and 180 days. These were performed to evaluate the behavior of granular microporous compositions in relation to bone neoformation. Through the performance obtained from in vivo assays, excellent osseointegration and bone tissue neoformation were observed. The results are encouraging and show that the microporous granular biomaterials of HA, β-TCP and biphasic compositions show similar results with perfect osseointegration. Architectures simulating a bone structure can make the difference between biomaterials for bone tissue replacement and repair.

  14. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review.

    NARCIS (Netherlands)

    Rathe, F.; Junker, R.; Chesnutt, B.C.; Jansen, J.A.

    2009-01-01

    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic

  15. Short-term skeletal and dental changes following bone-borne versus tooth-borne surgically assisted rapid maxillary expansion: a randomized clinical trial study.

    Science.gov (United States)

    Zandi, Mohammad; Miresmaeili, Amirfarhang; Heidari, Ali

    2014-10-01

    To evaluate and compare the short-term (post-retention) skeletal and dental changes following bone-borne and tooth-borne surgically assisted rapid maxillary expansion (SARME) using cone beam computed tomography (CBCT). In this randomized clinical study, 30 patients with transverse maxillary deficiency underwent either tooth-borne (n = 15) or bone-borne (n = 15) SARME. Before treatment and immediately after the consolidation period, CBCT was obtained and the nasal floor width, interdental root distance, palatal bone width and interdental cusp distance were measured at first premolar and first molar regions of maxilla. Twenty eight patients completed the study protocol. In both tooth-borne (n = 13) and bone-borne (n = 15) groups the highest degree of expansion occurred in the dental arch, followed by palatal bone, and nasal floor (V-shaped widening in coronal dimension). The amount and pattern of expansion was comparable between anterior and posterior maxillary regions in each group (parallel posteroanterior expansion) and between the two groups. Dental and skeletal effects of tooth-borne and bone-borne devices were comparable. The overall complication rate was negligible. Selection of an expansion device should be based on each individual patient's requirements. Future long-term clinical trial studies to evaluate the stability and relapse of these two techniques are recommended. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Study of in Vitro and in Vivo Bone Formation in Composite Cryogels and the Influence of Electrical Stimulation.

    Science.gov (United States)

    Mishra, Ruchi; Raina, Deepak Bushan; Pelkonen, Mea; Lidgren, Lars; Tägil, Magnus; Kumar, Ashok

    2015-01-01

    This work studies osteoinduction and bone conduction in polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC) biocomposite cryogels along with the synergistic effect of electrical stimulation. In vitro osteoinduction of C2C12 myoblast towards osteogenic lineage is demonstrated through alkaline phosphatase assay, scanning electron microscopy and energy dispersive X-ray spectroscopy. These results were followed by in vivo implantation studies of PTAC biocomposite cryogel scaffolds in the bone conduction chamber model depicting bone formation after 24 days based on immunohistological staining for osteogenic markers, i.e., collagen type I (Col I), osteocalcin (OCN), osteopontin (OPN) and bone sialoprotein (BSP). Further, osteogenic differentiation of murine mesenchymal stem cells was studied with and without electrical stimulation. The q-PCR analysis shows that the electrically stimulated cryogels exhibit ~ 6 folds higher collagen type I and ~ 10 folds higher osteopontin mRNA level, in comparison to the unstimulated cryogels. Thus, PTAC biocomposite cryogels present osteoinductive and osteoconductive properties during in vitro and in vivo studies and support osteogenic differentiation of mesenchymal stem cells under the influence of electrical stimulation.

  17. Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats.

    Science.gov (United States)

    Brasilino, Matheus da Silva; Stringhetta-Garcia, Camila Tami; Pereira, Camila Scacco; Pereira, Ariana Aparecida Ferreira; Stringhetta, Karina; Leopoldino, Andréia Machado; Crivelini, Marcelo Macedo; Ervolino, Edilson; Dornelles, Rita Cássia Menegati; de Melo Stevanato Nakamune, Ana Cláudia; Chaves-Neto, Antonio Hernandes

    2017-10-14

    The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum. Histometry evidenced an increase in bone area (P extraction. Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.

  18. Active and energy-dependent rapid formation of cell aggregates in the thermophilic photosynthetic bacterium Chloroflexus aggregans.

    Science.gov (United States)

    Hanada, Satoshi; Shimada, Keizo; Matsuura, Katsumi

    2002-03-05

    The thermophilic filamentous phototroph Chloroflexus aggregans was able to form a bacterial mat-like dense cell aggregate rapidly. The aggregate formation, which was observed in growing cells in a liquid medium in a bottle, occurred every time within 20-30 min after the cells were dispersed by shaking. The aggregation depended on the energy supplied by photosynthesis or respiration. Cells aggregated most rapidly under temperature and pH conditions that support maximum growth. The aggregation was also accelerated by the addition of 3-isobutyl-1-methylxanthine that inhibits cyclic 3',5'-AMP phosphodiesterase. Microscopic observation revealed that the bacterium has a fast gliding mobility (1-3 microm s(-1)). The distinctive cell aggregation of C. aggregans was due to this rapid gliding movement.

  19. The role of estrogen in bone growth and formation: changes at puberty

    Directory of Open Access Journals (Sweden)

    Divya Singh

    2010-12-01

    Full Text Available Divya Singh1, Sabyasachi Sanyal2, Naibedya Chattopadhyay11Division of Endocrinology, 2Division of Drug Target Discovery and Development, Central Drug Research Institute (Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, IndiaAbstract: A high peak bone mass (PBM at skeletal maturity is a good predictor for lower rate of fracture risks in later life. Growth during puberty contributes significantly to PBM achievement in women and men. The growth hormone (GH/insulin-like growth factor 1 (IGF-1 axis has a critical role in pubertal bone growth. There is an increase in GH and IGF-1 levels during puberty; thus, it is assumed that sex steroids contribute to higher GH/IGF-1 action during growth. Recent studies indicate that estrogen increases GH secretion in boys and girls, and the major effect of testosterone on GH secretion is via aromatization to estrogen. Estrogen is pivotal for epiphyseal fusion in young men and women. From studies of individuals with a mutated aromatase gene and a case study of male patient with defective estrogen receptor-alpha (ER-α, it is clear that estrogen is indispensable for normal pubertal growth and growth plate fusion. ER-α and estrogen receptor-beta (ER-β have been localized in growth plate and bone. ER knockout studies have shown that ER-α-/- female mice have reduced linear appendicular growth, while ER-β-/- mice have increased appendicular growth. No such effect is seen in ER-β-/- males; however, repressed growth is seen in ER-α-/- males, resulting in shorter long bones. Thus, ER-β represses longitudinal bone growth in female mice, while it has no function in the regulation of longitudinal bone growth in male mice. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.Keywords: peak bone mass, puberty, estrogen, growth plate

  20. Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system

    Science.gov (United States)

    Arnaud, Sara B.; Whalen, Robert T.; Fung, Paul; Sherrard, Donald J.; Maloney, Norma

    1992-01-01

    The -6-deg head-down tilt (HDT) is employed in the study of 8 subjects to determine early responses in human bone and calcium endocrines during spaceflight. The average rates of bone formation in the iliac crest are determined by means of a single-dose labeling schedule and are found to decrease in 6 of the subjects. The decrease varies directly with walking miles, and increased excretion of urinary Ca and Na are observed preceding increased levels of ionized serum calcium on a bed-rest day late in the week. Reduced phosphorous excretions are also followed by increased serum phosphorous on day six, and reductions are noted in parathyroid hormone and vitamin D by the end of the experiment. The data demonstrate the responsiveness of the skeletal system to biomechanical stimuli such as the HDT.

  1. Monostotic fibrous dysplasia of a lumbar vertebral body with secondary aneurysmal bone cyst formation: a case report

    Directory of Open Access Journals (Sweden)

    Snieders Marieke N

    2009-06-01

    Full Text Available Abstract We report the case of a 25-year-old Caucasian woman with symptomatic monostotic fibrous dysplasia of the fourth lumbar vertebral body. The patient suffered from a five-week history of progressive low back pain, radiating continuously to the left leg. Her medical history and physical and neurological examination did not demonstrate any significant abnormalities. Radiographs, computed tomography and magnetic resonance imaging revealed an osteolytic expansive lesion with a cystic component of the fourth lumbar vertebral body. Percutaneous transpedicular biopsy showed histological characteristics of fibrous dysplasia superimposed by the formation of aneurysmal bone cyst components. The patient was treated by subtotal vertebrectomy of the L4 vertebral body with anterior reconstruction and her postoperative course was uncomplicated. To our knowledge, this is the first reported case of a monostotic fibrous dysplasia with superimposed secondary aneurysmal bone cysts of a lumbar vertebral body.

  2. Synergistic enhancement of ectopic bone formation by supplementation of freshly isolated marrow cells with purified MSC in collagen-chitosan hydrogel microbeads.

    Science.gov (United States)

    Wise, Joel K; Alford, Andrea I; Goldstein, Steven A; Stegemann, Jan P

    2016-11-01

    Bone marrow-derived mesenchymal stem cells (MSC) can differentiate osteogenic lineages, but their tissue regeneration ability is inconsistent. The bone marrow mononuclear cell (BMMC) fraction of adult bone marrow contains a variety of progenitor cells that may potentiate tissue regeneration. This study examined the utility of BMMC, both alone and in combination with purified MSC, as a cell source for bone regeneration. Fresh BMMC, culture-expanded MSC, and a combination of BMMC and MSC were encapsulated in collagen-chitosan hydrogel microbeads for pre-culture and minimally invasive delivery. Microbeads were cultured in growth medium for 3 days, and then in either growth or osteogenic medium for 17 days prior to subcutaneous injection in the rat dorsum. MSC remained viable in microbeads over 17 days in pre-culture, while some of the BMMC fraction were nonviable. After 5 weeks of implantation, microCT and histology showed that supplementation of BMMC with MSC produced a strong synergistic effect on the volume of ectopic bone formation, compared to either cell source alone. Microbeads containing only fresh BMMC or only cultured MSC maintained in osteogenic medium resulted in more bone formation than their counterparts cultured in growth medium. Histological staining showed evidence of residual microbead matrix in undifferentiated samples and indications of more advanced tissue remodeling in differentiated samples. These data suggest that components of the BMMC fraction can act synergistically with predifferentiated MSC to potentiate ectopic bone formation. The microbead system may have utility in delivering desired cell populations in bone regeneration applications.

  3. HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation--a long-term histological study.

    Science.gov (United States)

    Schopper, Christian; Ziya-Ghazvini, Farzad; Goriwoda, Walter; Moser, Doris; Wanschitz, Felix; Spassova, Else; Lagogiannis, Georgios; Auterith, Alexandra; Ewers, Rolf

    2005-07-01

    In the present study, two biphasic calcium phosphate biomaterials (BCP) with HA/TCP ratios of 50/50 and 30/70 were obtained from a pure HA biomaterial. The biomaterials which showed the same three-dimensional geometry were implanted into corticocancellous costal defects of sheep. In the specimens of all three biomaterials, abundant bone formation, mineral dissolution from the biomaterial scaffolds, and active cellular resorption of the scaffolds was present after 6 and 12 months. Backscattered electron microscopy showed bone invasion into the pores of the scaffolds and micromechanical interlocking at the bone/biomaterial interface without intervening soft tissue. The pattern of bone formation and scaffold resorption was different for cortical and cancellous bone. No time-based effect, however, was observed. Overall, the BCP biomaterials had formed significantly more bone than the HA biomaterial. Also, scaffold resorption, which was followed by a replacement with newly formed bone, was significantly higher in the BCP biomaterials. Although no significant differences were observed between both BCP biomaterials, the present study had confirmed the assumption that HA/TCP compounding was suitable to improve bone formation and scaffold resorption in the investigated biomaterials and at the same time maintain the osteoconductive properties of the scaffolds. Copyright 2005 Wiley Periodicals, Inc.

  4. Commercial Honeybush (Cyclopia spp. Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages—An in vitro Study

    Directory of Open Access Journals (Sweden)

    Amcois Visagie

    2015-10-01

    Full Text Available Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL, produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9, tartrate resistant acid phosphatase (TRAP and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone.

  5. The fluoride coated AZ31B magnesium alloy improves corrosion resistance and stimulates bone formation in rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Wei; Zhang, Guangdao [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Tan, Lili; Yang, Ke [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Ai, Hongjun, E-mail: aihongjuna@sina.com [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China)

    2016-06-01

    This study aimed to evaluate the effect of fluorine coated Mg alloy and clarify its mechanism in bone formation. We implanted the fluorine coated AZ31B Mg alloy screw (group F) in rabbit mandibular and femur in vivo. Untreated AZ31B Mg alloy screw (group A) and titanium screw (group T) were used as control. Then, scanning electron microscopy, the spectral energy distribution analysis, hard and decalcified bone tissues staining were performed. Immunohistochemistry was employed to examine the protein expressions of bone morphogenetic protein 2 (BMP-2) and collagen type I in the vicinity of the implant. Compared with the group A, the degradation of the alloy was reduced, the rates of Mg corrosion and Mg ion release were slowed down, and the depositions of calcium and phosphate increased in the group F in the early stage of implantation. Histological results showed that fluorine coated Mg alloy had well osteogenic activity and biocompatibility. Moreover, fluoride coating obviously up-regulated the expressions of collagen type I and BMP-2. This study confirmed that the fluorine coating might improve the corrosion resistance of AZ31B Mg alloy and promote bone formation by up-regulated the expressions of collagen type I and BMP-2. - Highlights: • Fluoride coating inhibited the degradation of the alloy in the early implantation. • Fluorine coating could slow down the rate of Mg corrosion and Mg ion release. • Fluorine coating could promote the deposition of Ca and P in vivo. • Fluorine coated Mg alloy had well osteogenic activity and biocompatibility. • Fluorine coating up-regulated the expression of BMP-2 and collagen type I protein.

  6. Ectopic Bone Formation by Mesenchymal Stem Cells Derived from Human Term Placenta and the Decidua.

    Directory of Open Access Journals (Sweden)

    Gina D Kusuma

    Full Text Available Mesenchymal stem cells (MSCs are one of the most attractive cell types for cell-based bone tissue repair applications. Fetal-derived MSCs and maternal-derived MSCs have been isolated from chorionic villi of human term placenta and the decidua basalis attached to the placenta following delivery, respectively. Chorionic-derived MSCs (CMSCs and decidua-derived MSCs (DMSCs generated in this study met the MSCs criteria set by International Society of Cellular Therapy. These criteria include: (i adherence to plastic; (ii >90% expression of CD73, CD105, CD90, CD146, CD44 and CD166 combined with <5% expression of CD45, CD19 and HLA-DR; and (iii ability to differentiate into osteogenic, adipogenic, and chondrogenic lineages. In vivo subcutaneous implantation into SCID mice showed that both bromo-deoxyuridine (BrdU-labelled CMSCs and DMSCs when implanted together with hydroxyapatite/tricalcium phosphate particles were capable of forming ectopic bone at 8-weeks post-transplantation. Histological assessment showed expression of bone markers, osteopontin (OPN, osteocalcin (OCN, biglycan (BGN, bone sialoprotein (BSP, and also a marker of vasculature, alpha-smooth muscle actin (α-SMA. This study provides evidence to support CMSCs and DMSCs as cellular candidates with potent bone forming capacity.

  7. The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children.

    Science.gov (United States)

    Wawrzyk, Magdalena; Sokal, Jan; Andrzejewska, Ewa; Przewratil, Przemysław

    2015-01-01

    In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the

  8. Three-dimensional analysis of maxillary changes associated with facemask and rapid maxillary expansion compared with bone anchored maxillary protraction.

    Science.gov (United States)

    Hino, Claudia Toyama; Cevidanes, Lucia H S; Nguyen, Tung T; De Clerck, Hugo J; Franchi, Lorenzo; McNamara, James A

    2013-11-01

    Our objectives in this study were to evaluate in 3 dimensions the growth and treatment effects on the midface and the maxillary dentition produced by facemask therapy in association with rapid maxillary expansion (RME/FM) compared with bone-anchored maxillary protraction (BAMP). Forty-six patients with Class III malocclusion were treated with either RME/FM (n = 21) or BAMP (n = 25). Three-dimensional models generated from cone-beam computed tomographic scans, taken before and after approximately 1 year of treatment, were registered on the anterior cranial base and measured using color-coded maps and semitransparent overlays. The skeletal changes in the maxilla and the right and left zygomas were on average 2.6 mm in the RME/FM group and 3.7 mm in the BAMP group; these were different statistically. Seven RME/FM patients and 4 BAMP patients had a predominantly vertical displacement of the maxilla. The dental changes at the maxillary incisors were on average 3.2 mm in the RME/FM group and 4.3 mm in the BAMP group. Ten RME/FM patients had greater dental compensations than skeletal changes. This 3-dimensional study shows that orthopedic changes can be obtained with both RME/FM and BAMP treatments, with protraction of the maxilla and the zygomas. Approximately half of the RME/FM patients had greater dental than skeletal changes, and a third of the RME/FM compared with 17% of the BAMP patients had a predominantly vertical maxillary displacement. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-κB Activation, and IκBα Degradation

    Directory of Open Access Journals (Sweden)

    Shengnan Qin

    2015-11-01

    Full Text Available Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis.

  10. Bone bridge formation across the neuroforamen 14 years after instrumented fusion for isthmic spondylolisthesis?a case report

    OpenAIRE

    Lim, Joel Louis; Tan, Kimberly-Anne; Hey, Hwee Weng Dennis

    2017-01-01

    This case report describes the first case of a bone bridge formation across the left L5/S1 neuroforamen after instrumented posterolateral fusion for L5/S1 isthmic spondylolisthesis. Our patient was a 70-year-old lady who had grade 2, L5/S1 isthmic spondylolisthesis and bilateral S1 nerve root compression. She suffered from mechanical low back pain and neurogenic claudication, with radicular pain over both S1 dermatomes. She underwent in-situ, instrumented, posterolateral fusion and was asympt...

  11. Three-Dimensional Finite Element Analysis of Stress Distribution and Displacement of the Maxilla Following Surgically Assisted Rapid Maxillary Expansion with Tooth- and Bone-Borne Devices.

    Science.gov (United States)

    Dalband, Mohsen; Kashani, Jamal; Hashemzehi, Hadi

    2015-04-01

    The aim of this study was to investigate the displacement and stress distribution during surgically assisted rapid maxillary expansion under different surgical conditions with tooth- and bone-borne devices. Three-dimensional (3D) finite element model of a maxilla was constructed and an expansion force of 100 N was applied to the left and right molars and premolars with tooth-borne devices and the left and right of mid-palatal sutures at the first molar level with bone-borne devices. Five computer-aided design (CAD) models were simulated as follows and surgical procedures were used: G1: control group (without surgery); G2: Le Fort I osteotomy; G3: Le Fort I osteotomy and para-median osteotomy; G4: Le Fort I osteotomy and pterygomaxillary separation; and G5: Le Fort I osteotomy, para-median osteotomy, and pterygomaxillary separation. Maxillary displacement showed a gradual increase from G1 to G5 in all three planes of space, indicating that Le Fort I osteotomy combined with para-median osteotomy and pterygomaxillary separation produced the greatest displacement of the maxilla with both bone- and tooth-borne devices. Surgical relief and bone-borne devices resulted in significantly reduced stress on anchored teeth. Combination of Le Fort I and para-median osteotomy with pterygomaxillary separation seems to be an effective procedure for increasing maxillary expansion, and excessive stress side effects are lowered around the anchored teeth with the use of bone-borne devices.

  12. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells

    Science.gov (United States)

    Kalinkovich, Alexander; Itkin, Tomer; Ludin, Aya; Kao, Wei-Ming; Battista, Michela; Tesio, Melania; Kollet, Orit; Cohen, Neta Netzer; Margalit, Raanan; Buss, Eike C.; Baleux, Francoise; Oishi, Shinya; Fujii, Nobutaka; Larochelle, Andre; Dunbar, Cynthia E.; Broxmeyer, Hal E.; Frenette, Paul S.; Lapidot, Tsvee

    2014-01-01

    Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine SDF-1 to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady-state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4+ human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, while β2-adrenergic antagonist inhibited both steady-state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes. PMID:21494253

  13. Strategic camouflage treatment of skeletal Class III malocclusion (mandibular prognathism) using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy.

    Science.gov (United States)

    Seo, Yu-Jin; Lin, Lu; Kim, Seong-Hun; Chung, Kyu-Rhim; Nelson, Gerald

    2016-01-01

    This case report presents the camouflage treatment that successfully improved the facial profile of a patient with a skeletal Class III malocclusion using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy. The patient was an 18-year-old woman with chief complaints of crooked teeth and a protruded jaw. Camouflage treatment was chosen because she rejected orthognathic surgery under general anesthesia. A hybrid type of bone-borne rapid maxillary expander with palatal mini-implants was used to correct the transverse discrepancy, and a mandibular anterior subapical osteotomy was conducted to achieve proper overjet with normal incisal inclination and to improve her lip and chin profile. As a result, a Class I occlusion with a favorable inclination of the anterior teeth and a good esthetic profile was achieved with no adverse effects. Therefore, the hybrid type of bone-borne rapid maxillary expander and a mandibular anterior subapical osteotomy can be considered effective camouflage treatment of a skeletal Class III malocclusion, providing improved inclination of the dentition and lip profile. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  14. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    2015-01-12

    Jan 12, 2015 ... appliances (helical springs fabricated from 0.012‑inch stainless ... were monitored for infection and appliance failure throughout .... Many players are involved, including growth factors, inflammatory cytokines, antioxidants, bone breakdown cells (osteoclasts), bone‑building cells (osteoblasts), hormones, ...

  15. Effect of gentamicin loaded PMMA bone cement on Staphylococcus aureus biofilm formation

    NARCIS (Netherlands)

    Poelstra, KA; Busscher, HJ; Schenk, W; van Horn, [No Value; van der Mei, HC

    1999-01-01

    PMMA (poly-methyl-methacrylate) bone cement is widely used in prosthetic implant surgery and is currently prepared with vacuum-mixing for improved mechanical properties. Revision of implants due to infection occurs in about 1% of cases, mostly involving staphylococcal strains. Antibiotic loaded

  16. Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ditzel, Nicholas; Kassem, Moustapha

    2008-01-01

    , by employing human specific antibodies or in situ hybridization using human specific Alu-repeat probes. Recently, several methods have been developed to quantitate the newly formed bone using histomorphometric methods or using non-invasive imaging methods. This chapter describes the use of in vivo...

  17. Bone formation induced in an infant by systemic prostaglandin-E2 administration

    DEFF Research Database (Denmark)

    Jørgensen, H R; Svanholm, H; Høst, A

    1988-01-01

    We report a case of long-term systemic administration of prostaglandin E2 (PGE2) to a newborn infant with ductus-dependent congenital heart disease. After 46 days of treatment, radiography showed cortical hyperostosis of the long bones. The child died 62 days after discontinuation of prostaglandi...

  18. Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation

    NARCIS (Netherlands)

    Kisiel, M.; Klar, A.S.; Ventura, M.; Buijs, J.; Mafina, M.K.; Cool, S.M.; Hilborn, J.

    2013-01-01

    Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed

  19. Identification and analysis of genes involved in bone formation - a genetic approach in zebrafish -

    NARCIS (Netherlands)

    Spoorendonk, K.M.

    2009-01-01

    For many years bone research has been mainly performed in mice, chicken, cell culture systems, or human material from the clinic. In this thesis, we make use of the zebrafish (Danio rerio), a relatively new model system in this field. This small teleost offers possibilities which makes it a great

  20. Identification and analysis of genes involved in bone formation – a genetic approach in zebrafish –

    NARCIS (Netherlands)

    Spoorendonk, K.M.

    2009-01-01

    For many years bone research has been mainly performed in mice, chicken, cell culture systems, or human material from the clinic. In this thesis, we make use of the zebrafish (Danio rerio), a relatively new model system in this field. This small teleost offers possibilities which makes it a great

  1. Effect of polygonimitin C on bone formation and resorption in human ...

    African Journals Online (AJOL)

    Western blot assay was used to evaluate the effect of PC on the expressions of osterix (OSX), bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), fibronectin (FN), type I collagen (COL I), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) proteins in ...

  2. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  3. Modeling second-phase formation during rapid resolidification of stainless steel alloys

    Energy Technology Data Exchange (ETDEWEB)

    Elmer, J.W. (Lawrence Livermore National Lab., CA (USA)); Eagar, T.W.; Allen, S.M. (Massachusetts Inst. of Tech., Cambridge, MA (USA))

    1991-01-28

    Many common stainless steel (SS) alloy microstructures consist of a mixture of ferrite and austenite phases, however, when these alloys are rapidly resolidified using laser beam (LB) or electron beam (EB) processes they solidify in the single-phase-austenite or single-phase-ferrite mode. This paper investigates the influence of solidification rate on the reduction, and eventual elimination, of second phases during the rapid solidification of SS alloys. The influence of solidification rate on the ferrite content of these alloys was studied by calculating the dendrite-tip undercooling and then incorporating these results into a solute-redistribution model to calculate the relative fractions of primary and secondary phase that solidify from the melt. Single-phase solidification was predicted at high cooling rates and was confirmed through STEM analysis, showing solidification microstructures void of any significant microchemical composition gradients. Results showed a rapid-solidification model was used to calculate the relative fractions of primary and secondary phases that form during the resolidification of stainless steel alloys. The rapid-solidification model shows that the ferrite content of primary-austenite solidified alloys decreases and the ferrite content of primary-ferrite solidified alloys increases with increasing cooling rate. Results of the model indicate that primary-austenite alloys will solidify in the single-phase mode at all interface velocities greater than about 20 mm/s. This value correlates well with experiments. Results of the model indicate that primary-ferrite alloys will solidify in the single-phase mode at all interface velocities greater than about 50 mm/s. The experimentally-observed interface velocity for single-phase-ferrite solidification is significantly less (10 mm/s). This discrepancy is proposed to be related to the relative difficulty of nucleating austenite from the eutectic liquid. 13 refs., 5 figs., 2 tabs.

  4. Effects of prostaglandin F2 alpha on bone formation and resorption in cultured neonatal mouse calvariae: Role of prostaglandin E2 production

    Energy Technology Data Exchange (ETDEWEB)

    Raisz, L.G.; Alander, C.B.; Fall, P.M.; Simmons, H.A. (Univ. of Connecticut Health Center, Farmington (USA))

    1990-02-01

    Although most studies show that prostaglandin E2 (PGE2) is the most potent and effective of the prostanoids in bone, recent data in cell culture suggest that PGF2 alpha may have unique effects, particularly on cell replication. The present study was undertaken to compare the effects of PGF2 alpha and PGE2 in cultured neonatal mouse parietal bones by simultaneous measurement of bone resorption as release of previously incorporated 45Ca, bone formation as incorporation of (3H)proline into collagenase-digestible (CDP) and noncollagen protein, and DNA synthesis as incorporation of (3H)thymidine. PGF2 alpha was less effective than PGE2 as a stimulator of bone resorption, and its effects were partially inhibited by indomethacin and markedly inhibited by glucocorticoids. In contrast, the resorptive response to PGE2 was unaffected by indomethacin and only partially inhibited by cortisol. PGF2 alpha had little effect on bone formation, in contrast to the biphasic effect of PGE2, which inhibited labeling of CDP in the absence of cortisol and stimulated CDP labeling in the presence of cortisol. PGF2 alpha increased thymidine incorporation into DNA, but the effect was smaller than that of PGE2 and was inhibited by indomethacin. These observations suggested that PGF2 alpha might act in part by stimulating PGE2 production. By RIA, PGE2 concentrations were increased in the medium of bones treated with PGF2 alpha, and this increase was blocked by indomethacin. By HPLC, bones prelabeled with (3H)arachidonic acid showed an increase in labeled PGE2 release, and RIA showed an increase in PGE2 after PGF2 alpha treatment. These results indicate that PGF2 alpha is a relatively weak agonist in bone compared to PGE2 and that some of the effects of PGF2 alpha on bone resorption, formation, and cell replication may be mediated by an increase in endogenous PGE2 production.

  5. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    Science.gov (United States)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels; Garnero, Patrick; Pedersen, Per T; Ormstrup, Tina; Delaissé, Jean-Marie; Plesner, Torben

    2010-01-01

    Objectives: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions: Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. PMID:20528908

  6. Monitoring rapid valve formation in the pennate diatom Navicula salinarum (Bacillariophyceae)

    NARCIS (Netherlands)

    Hazelaar, S; van der Strate, HJ; Gieskes, WWC; Vrieling, EG

    After each division of a diatom cell, a new siliceous hypovalve is formed inside the silica deposition vesicle (SDV). We present the sequence of this early formation of the new valve in the pennate marine diatom Navicula salinarum (Grunow) Hustedt, visualized by using the fluorescent probe

  7. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

  8. Glucosamine and chondroitin sulfate association increases tibial epiphyseal growth plate proliferation and bone formation in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Roberta Bastos Wolff

    2014-01-01

    Full Text Available OBJECTIVE: The growth plate consists of organized hyaline cartilage and serves as a scaffold for endochondral ossification, a process that mediates longitudinal bone growth. Based on evidence showing that the oral administration of glucosamine sulfate (GS and/or chondroitin sulfate (CS is clinically valuable for the treatment of compromised articular cartilage, the current study evaluated the effects of these molecules on the tibial epiphyseal growth plate in female rats. METHOD: The animals were divided into two control groups, including vehicle treatment for 45 days (GC45 and 60 days (GC60 and six ovariectomized (OVX groups, including vehicle treatment for 45 days (GV45, GS for 45 days (GE45GS, GS+CS for 45 days (GE45GS+CS, vehicle for 60 days (GV60, GS for 60 days (GE60GS and GS+CS for 60 days (GE60GS+CS. At the end of treatment, the tibias were dissected, decalcified and processed for paraffin embedding. Morphological and morphometric methods were employed for analyzing the distal tibial growth plates using picrosirius red staining and the samples were processed for histochemical hyaluronan detection. Morphometric analyses were performed using the 6.0ProPlus¯ Image system. RESULTS: Notably, after 60 days of treatment, the number of proliferative chondrocytes increased two-fold, the percentage of remaining cartilage increased four-fold and the percentage of trabecular bone increased three-fold in comparison to the control animals. CONCLUSION: GS and CS treatment drugs led to marked cellular proliferation of the growth plate and bone formation, showing that drug targeting of the tibial epiphyseal growth plate promoted longitudinal bone growth.

  9. Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance and Lead to Significant Bone Tissue Formation

    Science.gov (United States)

    Cusella-De Angelis, Maria Gabriella; Laino, Gregorio; Piattelli, Adriano; Pacifici, Maurizio; De Rosa, Alfredo; Papaccio, Gianpaolo

    2007-01-01

    Background Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear. Methodology and Findings In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80–120 µm in diameter and 40–100 µm in depth, which we termed primary; and (ii) smaller microcavities of 10–20 µm in diameter and 3–10 µm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold. Conclusion In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and

  10. A new platelet cryoprecipitate glue promoting bone formation after ectopic mesenchymal stromal cell-loaded biomaterial implantation in nude mice.

    Science.gov (United States)

    Trouillas, Marina; Prat, Marie; Doucet, Christelle; Ernou, Isabelle; Laplace-Builhé, Corinne; Blancard, Patrick Saint; Holy, Xavier; Lataillade, Jean-Jacques

    2013-01-04

    This study investigated the promising effect of a new Platelet Glue obtained from Cryoprecipitation of Apheresis Platelet products (PGCAP) used in combination with Mesenchymal Stromal Cells (MSC) loaded on ceramic biomaterials to provide novel strategies enhancing bone repair. PGCAP growth factor content was analyzed by ELISA and compared to other platelet and plasma-derived products. MSC loaded on biomaterials (65% hydroxyapatite/35% beta-TCP or 100% beta-TCP) were embedded in PGCAP and grown in presence or not of osteogenic induction medium for 21 days. Biomaterials were then implanted subcutaneously in immunodeficient mice for 28 days. Effect of PGCAP on MSC was evaluated in vitro by proliferation and osteoblastic gene expression analysis and in vivo by histology and immunohistochemistry. We showed that PGCAP, compared to other platelet-derived products, allowed concentrating large amount of growth factors and cytokines which promoted MSC and osteoprogenitor proliferation. Next, we found that PGCAP improves the proliferation of MSC and osteogenic-induced MSC. Furthermore, we demonstrated that PGCAP up-regulates the mRNA expression of osteogenic markers (Collagen type I, Osteonectin, Osteopontin and Runx2). In vivo, type I collagen expressed in ectopic bone-like tissue was highly enhanced in biomaterials embedded in PGCAP in the absence of osteogenic pre-induction. Better results were obtained with 65% hydroxyapatite/35% beta-TCP biomaterials as compared to 100% beta-TCP. We have demonstrated that PGCAP is able to enhance in vitro MSC proliferation, osteoblastic differentiation and in vivo bone formation in the absence of osteogenic pre-induction. This clinically adaptable platelet glue could be of interest for improving bone repair.

  11. Insight into the transgenerational effect of benzo[a]pyrene on bone formation in a teleost fish (Oryzias latipes).

    Science.gov (United States)

    Seemann, Frauke; Peterson, Drew R; Witten, P Eckhard; Guo, Bao-Sheng; Shanthanagouda, Adamane H; Ye, Rui R; Zhang, Ge; Au, Doris W T

    2015-12-01

    Recent cross-generational studies in teleost fish have raised the awareness that high levels of benzo[a]pyrene (BaP) could affect skeletal integrity in the directly exposed F0 and their F1-F2. However, no further details were provided about the causes for abnormalities on the molecular and cellular level and the persistence of such sub-organismal impairments at the transgenerational scale (beyond F2). Adult Oryzias latipes were exposed to 1μg/L BaP for 21days. The F1-F3 were examined for skeletal deformities, histopathological alterations of vertebral bodies and differential expression of key genes of bone metabolism. Significant increase of dorsal-ventral vertebral compression was evident in ancestrally exposed larvae. Histopathological analysis revealed abnormal loss of notochord sheath, a lack of notochord epithelial integrity, reduced bone tissue and decreased osteoblast abundance. A significant downregulation of ATF4 and/or osterix and a high biological variability of COL10, coupled with a significant deregulation of SOX9a/b in the F1-F3 suggest that ancestral BaP exposure most likely perturbed chordoblasts, chondroblast and osteoblast differentiation, resulting in defective notochord sheath repair and rendering the vertebral column more vulnerable to compression. The present findings provide novel molecular and cellular insights into BaP-induced transgenerational bone impairment in the unexposed F3. From the ecological risk assessment perspective, BaP needs to be regarded as a transgenerational skeletal toxicant, which exerts a far-reaching impact on fish survival and fitness. Given that basic mechanisms of cartilage/bone formation are conserved between medaka and mammals, the results may also shed light on the potential transgenerational effect of BaP on the genesis of skeletal diseases in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Body fat loss induced by calcium in co-supplementation with conjugated linoleic acid is associated with increased expression of bone formation genes in adult mice.

    Science.gov (United States)

    Chaplin, Alice; Palou, Andreu; Serra, Francisca

    2015-12-01

    The potential of conjugated linoleic acids (CLA) and calcium in weight management in animal models and human studies has been outlined, as well as their use to prevent bone loss at critical stages. In addition, it has been suggested that bone remodeling and energy metabolism are regulated by shared pathways and involve common hormones such as leptin. We have previously shown that supplementation with CLA and calcium in adult obese mice decreases body weight and body fat. The aim of the present study was to assess the effects of these two compounds on bone and energy metabolism markers on bone. Mice (C57BL/6J) were divided into five groups according to diet and treatment (up to 56 days): control (C), high-fat diet (HF), HF+CLA (CLA), HF+calcium (Ca) and HF with both compounds (CLA+Ca). At the end of treatment, bone formation markers were determined in plasma and expression of selected bone and energy markers was determined in tibia by quantitative polymerase chain reaction. Results show that CLA was associated with decreased tibia weight and minor impact on bone markers, whereas calcium, either alone or co-supplemented with CLA, maintained bone weight and promoted the expression of bone formation genes such as bone gamma-carboxyglutamate protein 2 (Bglap2) and collagen Iα1 (Col1a1). Furthermore, it had a significant effect on key players in energy metabolism, in particular leptin and adiponectin tibia receptors. Overall, in addition to the weight loss promoting properties of calcium, on its own or co-supplemented with CLA, our results support beneficial effects on bone metabolism in mice. Copyright © 2015. Published by Elsevier Inc.

  13. Bone bridge formation across the neuroforamen 14 years after instrumented fusion for isthmic spondylolisthesis-a case report.

    Science.gov (United States)

    Lim, Joel Louis; Tan, Kimberly-Anne; Hey, Hwee Weng Dennis

    2017-03-01

    This case report describes the first case of a bone bridge formation across the left L5/S1 neuroforamen after instrumented posterolateral fusion for L5/S1 isthmic spondylolisthesis. Our patient was a 70-year-old lady who had grade 2, L5/S1 isthmic spondylolisthesis and bilateral S1 nerve root compression. She suffered from mechanical low back pain and neurogenic claudication, with radicular pain over both S1 dermatomes. She underwent in-situ, instrumented, posterolateral fusion and was asymptomatic for more than 13 years before developing progressive onset of left radicular pain over the L5 dermatome. Imaging revealed a bisected left L5/S1 neuroforamen secondary to a bone bridge formation resulting in stenosis. The pars defect in this case may have had sufficient osteogenic and osteoinductive factors to heal following spinal stabilization. Although in-situ posterolateral fusion is an accepted surgical treatment for isthmic spondylolisthesis, surgeons should consider reduction of the spondylolisthesis and excision of the pars defects to avoid this possible long-term complication.

  14. Effect of bone-borne rapid maxillary expanders with and without surgical assistance on the craniofacial structures using finite element analysis.

    Science.gov (United States)

    Lee, Seong Cheon; Park, Jae Hyun; Bayome, Mohamed; Kim, Ki Beom; Araujo, Eustaquio A; Kook, Yoon-Ah

    2014-05-01

    The aim of this study was to analyze stress distribution and displacement of the craniofacial structures resulting from bone-borne rapid maxillary expanders with and without surgical assistance using finite element analysis. Five designs of rapid maxillary expanders were made: a tooth-borne hyrax expander (type A); a bone-borne expander (type B); and 3 bone-borne surgically assisted modalities: separation of the midpalatal suture (type C), added separation of the pterygomaxillary sutures (type D), and added LeFort I corticotomy (type E). The geometric nonlinear theory was applied to evaluate the Von Mises stress distribution and displacement. The surgical types C, D, and E demonstrated more transverse movement than did the nonsurgical types A and B. The amounts of expansion were greater in the posterior teeth in types A and B, but in types C, D, and E, the amounts of expansion were greater in the anterior teeth. At the midpalatal suture, the nonsurgical types showed more anterior expansion than did the posterior region, and higher stresses than with the surgical types. Type B showed the highest stresses at the infraorbital margin, anterior and posterior nasal spines, maxillary tuberosity, and pterygoid plate and hamulus. The 3 surgical models showed similar amounts of stress and displacement along the teeth, midpalatal sutures, and craniofacial sutures. Therefore, when using a bone-borne rapid maxillary expander in an adult, it is recommended to assist it with midpalatal suture separation, which requires minimal surgical intervention. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  15. Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats.

    Science.gov (United States)

    Gad Allam, Hayam Ibrahim

    2016-01-01

    To determine the systemic effect of sclerostin monoclonal antibody (Scl-AbIII) administration on markers of bone formation and compare it with a combination of sclerostin antibody and raloxifene. Experimental study. Medical College Animal House at King Khaled University Hospital, Riyadh, Saudi Arabia, from January to November 2014. Forty-five female rats were divided into 5 groups equally; 1 control group and 4 groups of ovariectomized (OVX) rats: control OVX rats and OVX rats treated by Scl-AbIII, raloxifene or Scl-AbIII+raloxifene one month after ovariectomy, continued for 4 weeks. At the end of treatment, serum levels of Bone Specific Alkaline Phosphatase (BSAP), alkaline phosphatase, osteocalcin, Insulin-like Growth Factor-1 (IGF-1), Parathyroid Hormone (PTH), Ca2+ and phosphorus were measured. Uterus was weighed and body weight change was calculated. Scl-AbIII or raloxifene treatment produced significant increase of serum BSAP, osteocalcin, IGF-1, PTH and Ca2+ levels. Raloxifene, either alone or combined with Scl-AbIII attenuated the decrease in uterus wet weight, and the increase in body weight seen in OVX rats. Combination therapy of Scl-AbIII, and raloxifene produced significant increase of serum alkaline phosphatase, osteocalcin and IGF-1 levels than treatment with either Scl-AbIII or raloxifene alone. Combination therapy of Scl-AbIII and raloxifene is an attractive strategy to enhance bone formation and can offer better gain over treatment with either one of them alone. Confirmation of these preliminary observations must await careful long-term studies.

  16. High fat diet rapidly suppresses B lymphopoiesis by disrupting the supportive capacity of the bone marrow niche.

    Directory of Open Access Journals (Sweden)

    Benjamin J Adler

    Full Text Available The bone marrow (BM niche is the primary site of hematopoiesis, and cues from this microenvironment are critical to maintain hematopoiesis. Obesity increases lifetime susceptibility to a host of chronic diseases, and has been linked to defective leukogenesis. The pressures obesity exerts on hematopoietic tissues led us to study the effects of a high fat diet (HFD: 60% Kcal from fat on B cell development in BM. Seven week old male C57Bl/6J mice were fed either a high fat (HFD or regular chow (RD diet for periods of 2 days, 1 week and 6 weeks. B-cell populations (B220+ were not altered after 2 d of HFD, within 1 w B-cell proportions were reduced by -10%, and by 6 w by -25% as compared to RD (p<0.05. BM RNA was extracted to track the expression of B-cell development markers Il-7, Ebf-1 and Pax-5. At 2 d, the expression of Il-7 and Ebf-1 were reduced by -20% (p = 0.08 and -11% (p = 0.06 whereas Pax-5 was not significantly impacted. At one week, however, the expressions of Il-7, Ebf-1, and Pax-5 in HFD mice fell by -19%, -20% and -16%, and by six weeks were further reduced to -23%, -29% and -34% as compared to RD (p<0.05 for all, a suppression paralleled by a +363% increase in adipose encroachment within the marrow space (p<0.01. Il-7 is a critical factor in the early B-cell lineage which is secreted by supportive cells in the BM niche, and is necessary for B-cell commitment. These data indicate that BM Il-7 expression, and by extension B-cell differentiation, are rapidly impaired by HFD. The trend towards suppressed expression of Il-7 following only 2 d of HFD demonstrates how susceptible the BM niche, and the cells which rely on it, are to diet, which ultimately could contribute to disease susceptibility in metabolic disorders such as obesity.

  17. ESR study of MMA polymerization by a peroxide/amine system: bone cement formation.

    Science.gov (United States)

    Oldfield, F F; Yasuda, H K

    1999-03-15

    Electron spin resonance (ESR) spectroscopy was used to gain insight at the molecular level into the curing of bone cement. Methyl methacrylate was polymerized using a N,N-dimethyl-p-toluidine (TD)/benzoyl peroxide (BPO) redox system in the presence of polymethyl methacrylate (PMMA) powder. The conventional nine-line ESR spectrum for the growing polymer radical was detected at the gel stage of polymerization. While the optimum free radical concentration was observed near the equimolar amine/BPO concentration, excess amine led to a change in the chemical structure of the trapped radical and inhibited the polymerization process. At a high amine/BPO ratio the nine-line signal disappeared and a three-line nitroxide-based radical appeared. The appearance of this nitroxide signal seems to depend on the amine/BPO molar ratio and on the presence of PMMA. An excess amount of amine with respect to BPO was found to inhibit the polymerization process. When BPO was removed, the system still polymerized but with a longer gelation time and a lower radical concentration. These results demonstrate that trapped free radicals in the bulk polymerization of MMA convert to polymeric peroxides that act as initiators in bone cement. When the accelerator 4-dimethylamino phenethyl alcohol (TDOH) was used, a higher radical concentration was observed in the polymerizing system. TDOH shows potential for being a more effective accelerator than TD for bone cement curing. Copyright 1999 John Wiley & Sons, Inc.

  18. Bio-silica and bio-polyphosphate: applications in biomedicine (bone formation).

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Wiens, Matthias; Ushijima, Hiroshi; Müller, Werner E G

    2012-08-01

    Bio-silica represents the main mineral component of the sponge skeletal elements (siliceous spicules), while bio-polyphosphate (bio-polyP), a multifunctional polymer existing in microorganisms and animals acts, among others, as reinforcement for pores in cell membranes. These natural inorganic bio-polymers, which can be readily prepared, either by recombinant enzymes (bio-silica and bio-polyP) or chemically (polyP), are promising materials/substances for the amelioration and/or treatment of human bone diseases and dysfunctions. It has been demonstrated that bio-silica causes in vitro a differential effect on the expression of the genes OPG and RANKL, encoding two mediators that control the tuned interaction of the anabolic (osteoblasts) and catabolic (osteoclasts) pathways in human bone cells. Since bio-silica and bio-polyP also induce the expression of the key mediator BMP2 which directs the differentiation of bone-forming progenitor cells to mature osteoblasts and in parallel inhibits the function of osteoclasts, they are promising candidates for treatment of osteoporosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Relating cell proliferation to in vivo bone formation in porous Ca/P scaffolds.

    Science.gov (United States)

    van Gaalen, Steven M; de Bruijn, Joost D; Wilson, Clayton E; van Blitterswijk, Clemens A; Verbout, Abraham J; Alblas, Jacqueline; Dhert, Wouter J A

    2010-01-01

    Most current methods for cell monitoring on 3D porous scaffolds involve end-stage investigation of scaffolds. Repeated measurements on scaffolds, without disturbing cell vitality and proliferation, are needed to relate in vitro to in vivo data. Alamar Blue was used for this purpose. Two different Ca/P scaffolds were studied, using rat BMSCs with three different seeding densities [2.5 x 10(4) (SD1), 2.5 x 10(5) (SD2), 2.5 x 10(6) (SD3) cells]. Alamar Blue readings were done on days 1, 3, 5 and 7. After 7 days all 96 scaffolds (n = 16) were implanted in 16 mice for 4 weeks. Bone histomorphometry was performed. For both scaffolds, seeding efficiencies were highest with SD1 and SD2, cell proliferation was optimal in SD1, whereas SD3 resulted in an initial drop in vital cell number in the first 3 days. In vivo, upscaling from SD1 to SD2 lead to significantly more bone contact% in both scaffolds. Alamar Blue was shown to be a valuable tool in relating in vitro to in vivo data. Cell proliferation may differ depending on seeding density and scaffold type used. Seeding more cells may not necessarily result in more in vivo bone contact%.

  20. Spontaneous bone formation on the maxillary sinus floor in association with surgery to remove a migrated dental implant: a case report.

    Science.gov (United States)

    Scarano, A; Piattelli, A; Iezzi, G; Varvara, G

    2014-10-01

    A variety of surgical techniques have been developed to reconstruct the posterior maxilla when bone volume is insufficient. For some decades, sinus augmentation, using various bone substitutes, has been used to reconstruct the posterior maxilla for dental implant placement. Even if new bone formation is achieved in the sinus after bone grafting, the possibility of new bone formation with only a membrane elevation in the maxillary sinus has been reported in human and animal studies. The aim of this case report was to document an unexpected healing pattern after the removal of a dental implant migrated in the maxillary sinus. In October 2009 a 49-year-old man with a partially edentulous maxilla underwent implant placement. Specifically, a total of 5 implants were inserted, 2 in the left and 3 in the right posterior maxilla. Four months later, at the time of abutment connection, the implant at the site of the maxillary left first molar was accidentally pushed in the sinus. A surgical removal of the implant from the maxillary sinus was proposed and the patient consented to the surgical intervention. Computed axial tomography (CAT) scan images revealed opacification of the left maxillary sinus with mucosal thickening, and the dental implant displaced within the sinus. The planned treatment sequence was: 1) removal of the implant; 2) sinus augmentation procedure after 5 months; 3) implant insertion 5 months after the bone graft. The implant was removed. Five months later, the patient was admitted for the bone-grafting augmentation procedure. A new CAT scan image revealed normal mucosal thickness and no opacification of the left maxillary sinus; bone formation was evident. The surgery was undertaken with local anesthesia and conscious sedation. At reentry, the sinus wall was found to be totally healed. Newly formed bone (21.2%) with wide osteocyte lacunae and large marrow spaces (73.8%) were present with newly formed vessels and no inflammatory cell infiltrate. The

  1. Rapid formation of massive black holes in close proximity to embryonic protogalaxies

    Science.gov (United States)

    Regan, John A.; Visbal, Eli; Wise, John H.; Haiman, Zoltán; Johansson, Peter H.; Bryan, Greg L.

    2017-03-01

    The appearance of supermassive black holes at very early times1-3 in the Universe is a challenge to our understanding of star and black hole formation. The direct-collapse4,5 black hole scenario provides a potential solution. A prerequisite for forming a direct-collapse black hole is that the formation of (much less massive) population III stars be avoided6,7; this can be achieved by destroying H2 by means of Lyman-Werner radiation (photons of energy around 12.6 eV). Here we show that two conditions must be met in the protogalaxy that will host the direct-collapse black hole. First, prior star formation must be delayed; this can be achieved with a background Lyman-Werner flux of JBG ≳ 100J21 (J21 is the intensity of background radiation in units of 10-21 erg cm-2 s-1 Hz-1 sr-1). Second, an intense burst of Lyman-Werner radiation from a neighbouring star-bursting protogalaxy is required, just before the gas cloud undergoes gravitational collapse, to suppress star formation completely. Using high-resolution hydrodynamical simulations that include full radiative transfer, we find that these two conditions inevitably move the host protogalaxy onto the isothermal atomic cooling track, without the deleterious effects of either photo-evaporating the gas or polluting it with heavy elements. These atomically cooled, massive protogalaxies are expected ultimately to form a direct-collapse black hole of mass 104-105M⊙.

  2. Rapid formation of isoprene photo-oxidation products observed in Amazonia

    Directory of Open Access Journals (Sweden)

    T. Karl

    2009-10-01

    Full Text Available Isoprene represents the single most important reactive hydrocarbon for atmospheric chemistry in the tropical atmosphere. It plays a central role in global and regional atmospheric chemistry and possible climate feedbacks. Photo-oxidation of primary hydrocarbons (e.g. isoprene leads to the formation of oxygenated VOCs (OVOCs. The evolution of these intermediates affects the oxidative capacity of the atmosphere (by reacting with OH and can contribute to secondary aerosol formation, a poorly understood process. An accurate and quantitative understanding of VOC oxidation processes is needed for model simulations of regional air quality and global climate. Based on field measurements conducted during the Amazonian Aerosol Characterization Experiment (AMAZE-08 we show that the production of certain OVOCs (e.g. hydroxyacetone from isoprene photo-oxidation in the lower atmosphere is significantly underpredicted by standard chemistry schemes. Recently reported fast secondary production could explain 50% of the observed discrepancy with the remaining part possibly produced via a novel primary production channel, which has been proposed theoretically. The observations of OVOCs are also used to test a recently proposed HOx recycling mechanism via degradation of isoprene peroxy radicals. If generalized our observations suggest that prompt photochemical formation of OVOCs and other uncertainties in VOC oxidation schemes could result in uncertainties of modelled OH reactivity, potentially explaining a fraction of the missing OH sink over forests which has previously been largely attributed to a missing source of primary biogenic VOCs.

  3. Vasoactive intestinal polypeptide excites medial pontine reticular formation neurons in the brainstem rapid eye movement sleep-induction zone

    DEFF Research Database (Denmark)

    Kohlmeier, Kristi Anne; Reiner, P B

    1999-01-01

    Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key...... conclude that VIP excites mPRF neurons by activation of a sodium current. This effect is mediated at least in part by G-protein stimulation of adenylyl cyclase, cAMP, and protein kinase A. These data suggest that VIP may play a physiological role in REM induction by its actions on mPRF neurons....

  4. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation.

    Science.gov (United States)

    Xue, Feng; Wu, Er-Jun; Zhang, Pei-Xun; Li-Ya, A; Kou, Yu-Hui; Yin, Xiao-Feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  5. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  6. Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li

    2015-01-01

    Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...... for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo...... that pharmacological inhibition of PRKG1 in hMSC implanted at the site of bone defect can enhance bone regeneration. Stem Cells 2015....

  7. Efficiency of high molecular weight backbone degradable HPMA copolymer-prostaglandin E1 conjugate in promotion of bone formation in ovariectomized rats.

    Science.gov (United States)

    Pan, Huaizhong; Sima, Monika; Miller, Scott C; Kopečková, Pavla; Yang, Jiyuan; Kopeček, Jindřich

    2013-09-01

    Multiblock, high molecular weight, linear, backbone degradable HPMA copolymer-prostaglandin E1 (PGE1) conjugate has been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA), which contains an enzymatically degradable oligopeptide sequence flanked by two dithiobenzoate groups, followed by postpolymerization aminolysis and thiol-ene chain extension. The multiblock conjugate contains Asp8 as the bone targeting moiety and enzymatically degradable bonds in the polymer backbone; in vivo degradation produces cleavage products that are below the renal threshold. Using an ovariectomized (OVX) rat model, the accumulation in bone and efficacy to promote bone formation was evaluated; low molecular weight conjugates served as control. The results indicated a higher accumulation in bone, greater enhancement of bone density, and higher plasma osteocalcin levels for the backbone degradable conjugate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Efficiency of High Molecular Weight Backbone Degradable HPMA Copolymer – Prostaglandin E1 Conjugate in Promotion of Bone Formation in Ovariectomized Rats

    Science.gov (United States)

    Pan, Huaizhong; Sima, Monika; Miller, Scott C.; Kopečková, Pavla; Yang, Jiyuan; Kopeček, Jindřich

    2013-01-01

    Multiblock, high molecular weight, linear, backbone degradable HPMA copolymer-prostaglandin E1 (PGE1) conjugate has been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA), which contains an enzymatically degradable oligopeptide sequence flanked by two dithiobenzoate groups, followed by post-polymerization aminolysis and thiol-ene chain extension. The multiblock conjugate contains Asp8 as the bone-targeting moiety and enzymatically degradable bonds in the polymer backbone; in vivo degradation produces cleavage products that are below the renal threshold. Using an ovariectomized (OVX) rat model, the accumulation in bone and efficacy to promote bone formation was evaluated; low molecular weight conjugates served as control. The results indicated a higher accumulation in bone, greater enhancement of bone density, and higher plasma osteocalcin levels for the backbone degradable conjugate. PMID:23731780

  9. Altered composition of bone as triggered by irradiation facilitates the rapid erosion of the matrix by both cellular and physicochemical processes.

    Directory of Open Access Journals (Sweden)

    Danielle E Green

    Full Text Available Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the 'biologically orchestrated' resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice exposed to 5 Gy of Cs(137 γ-irradiation were compared to age-matched control at 2d, 10d, or 8w following exposure. By 10d, irradiation had led to significant loss of trabecular bone volume fraction. Assessed by reflection-based Fourier transform infrared imaging (FTIRI, chemical composition of the irradiated matrix indicated that mineralization had diminished at 2d by -4.3±4.8%, and at 10d by -5.8±3.2%. These data suggest that irradiation facilitates the dissolution of the matrix through a change in the material itself, a conclusion supported by a 13.7±4.5% increase in the elastic modulus as measured by nanoindentation. The decline in viable cells within the marrow of irradiated mice at 2d implies that the immediate collapse of bone quality and inherent increased risk of fracture is not solely a result of an overly-active biologic process, but one fostered by alterations in the material matrix that predisposes the material to erosion.

  10. Progesterone and Bone: Actions Promoting Bone Health in Women

    Directory of Open Access Journals (Sweden)

    Vanadin Seifert-Klauss

    2010-01-01

    Full Text Available Estradiol (E2 and progesterone (P4 collaborate within bone remodelling on resorption (E2 and formation (P4. We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2 and onset of ovulation (P4 both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD related to subclinical ovulatory disturbances (SODs. Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.

  11. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats.

    Science.gov (United States)

    Zhang, Dan; Gao, Peng; Li, Qin; Li, Jinda; Li, Xiaojuan; Liu, Xiaoning; Kang, Yunqing; Ren, Liling

    2017-06-05

    There is a critical need for the management of large bone defects. The purpose of this study was to engineer a biomimetic periosteum and to combine this with a macroporous β-tricalcium phosphate (β-TCP) scaffold for bone tissue regeneration. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were harvested and cultured in different culture media to form undifferentiated rBMSC sheets (undifferentiated medium (UM)) and osteogenic cell sheets (osteogenic medium (OM)). Simultaneously, rBMSCs were differentiated to induced endothelial-like cells (iECs), and the iECs were further cultured on a UM to form a vascularized cell sheet. At the same time, flow cytometry was used to detect the conversion rates of rBMSCs to iECs. The pre-vascularized cell sheet (iECs/UM) and the osteogenic cell sheet (OM) were stacked together to form a biomimetic periosteum with two distinct layers, which mimicked the fibrous layer and cambium layer of native periosteum. The biomimetic periostea were wrapped onto porous β-TCP scaffolds (BP/β-TCP) and implanted in the calvarial bone defects of rats. As controls, autologous periostea with β-TCP (AP/β-TCP) and β-TCP alone were implanted in the calvarial defects of rats, with a no implantation group as another control. At 2, 4, and 8 weeks post-surgery, implants were retrieved and X-ray, microcomputed tomography (micro-CT), histology, and immunohistochemistry staining analyses were performed. Flow cytometry results showed that rBMSCs were partially differentiated into iECs with a 35.1% conversion rate in terms of CD31. There were still 20.97% rBMSCs expressing CD90. Scanning electron microscopy (SEM) results indicated that cells from the wrapped cell sheet on the β-TCP scaffold apparently migrated into the pores of the β-TCP scaffold. The histology and immunohistochemistry staining results from in vivo implantation indicated that the BP/β-TCP and AP/β-TCP groups promoted the formation of blood vessels and new bone tissues in the bone

  12. Rapid Formation of 1D Titanate Nanotubes Using Alkaline Hydrothermal Treatment and Its Photocatalytic Performance

    Directory of Open Access Journals (Sweden)

    Chin Wei Lai

    2015-01-01

    Full Text Available One-dimensional (1D titanate nanotubes (TNT were successfully synthesized using alkaline hydrothermal treatment of commercial TiO2 nanopowders in a Teflon lined stainless steel autoclave at 150°C. The minimum time required for the formation of the titanate nanotubes was 9 h significantly. After the hydrothermal processing, the layered titanate was washed with acid and water in order to control the amount of Na+ ions remaining in the sample solutions. In this study, the effect of different reaction durations in a range of 3 h to 24 h on the formation of nanotubes was carried out. As the reaction duration is extended, the changes in structure from particle to tubular shapes of alkaline treated TiO2 were obtained via scanning electron microscope (SEM. Also, the significant impact on the phase transformation and crystal structure of TNT was characterized through XRD and Raman analysis. Indeed, the photocatalytic activity of TNT was investigated through the degradation of methyl orange aqueous solution under the ultraviolet light irradiation. As a result, TNT with reaction duration at 6 h has a better photocatalytic performance than other samples which was correlated to the higher crystallinity of the samples as shown in XRD patterns.

  13. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing

    Science.gov (United States)

    Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice GT; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D.

    2017-01-01

    during fracture repair, but it plays an important role in coordinating chondrocyte, osteoclast, and endothelial responses that all contribute to the endochondral bone formation required for normal fracture repair. PMID:25801198

  14. Regulation of bone formation by baicalein via the mTORC1 pathway

    Directory of Open Access Journals (Sweden)

    Li SF

    2015-09-01

    Full Text Available Sheng-fa Li,1,2,* Jia-jun Tang,1,2,* Jian Chen,1–3,* Pei Zhang,4,* Ting Wang,5 Tian-yu Chen,1,2 Bo Yan,1,2 Bin Huang,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Zhong-min Zhang,1,2 Da-di Jin1,21Academy of Orthopedics of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Three Gorges Central Hospital of Chongqing, Chongqing, People’s Republic of China; 4School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L, to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1 signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2, in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months

  15. Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic rhBMP-2 and anti-resorptive agents.

    Science.gov (United States)

    Yu, N Y C; Gdalevitch, M; Murphy, C M; Mikulec, K; Peacock, L; Fitzpatrick, J; Cantrill, L C; Ruys, A J; Cooper-White, J J; Little, D G; Schindeler, A

    2014-01-31

    Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 µg) ± anti-resorptive agents: zoledronic acid (5 µg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 µg ZA/2% HA) or IkappaB kinase (IKK) inhibitor (10 µg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3% TV, p augmented rhBMP-induced bone formation.

  16. 3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

    Science.gov (United States)

    Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

    2017-07-17

    Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

  17. A novel Rapid Additive Manufacturing concept for architectural composite shell construction inspired by the shell formation in land snails.

    Science.gov (United States)

    Felbrich, Benjamin; Wulle, Frederik; Allgaier, Christoph; Menges, Achim; Verl, Alexander; Wurst, Karl-Heinz; Nebelsick, James

    2018-01-04

    State of the art rapid additive manufacturing (RAM), specifically Fused Filament Fabrication (FFF) has gained popularity among architects, engineers and designers for quick prototyping of technical devices, rapid production of small series and even construction scale fabrication of architectural elements. The spectrum of producible shapes and the resolution of detail, however, are determined and constrained by the layer-based nature of the fabrication process. These aspects significantly limit FFF-based approaches for the prefabrication and in-situ fabrication of freeform shells at the architectural scale. Snails exhibit a shell building process that suggests ways to overcome these limits. They produce a soft, pliable proteinaceous film - the periostracum - which later hardens and serves, among other functions, as a form-giving surface for an inner calcium carbonate layer. Snail shell formation behavior is interpreted from a technical point of view to extract potentially useful aspects for a biomimetic transfer. A RAM concept for continuous extrusion of thin free form composite shells inspired by the snail shell formation is presented. © 2018 IOP Publishing Ltd.

  18. Design of a biological method for rapid detection of presence of PCR inhibitors in aged bone DNA.

    Science.gov (United States)

    Ghasemi, Akram; Mahdieh, Nejat; Tavallaei, Mahmood; Aslani, Mohammad Mehdi; Zafari, Zahra; Shirkavand, Atefeh; Farzad, Maryam Sharafi; Naderi, Mahdi; Azariyan, Sajjad Habibi; Zeinali, Sirous

    2012-01-01

    Molecular human identification is one of the most important tests performed in forensic laboratories. Some of these tests are applied for identification of human remains from natural disasters, wars, etc., but problems may occur as a result of DNA degradation and external DNA contamination. We investigated effects of bacterial DNA on identifying the presence or absence of PCR inhibitors in aged bone DNA. DNA samples were extracted from blood, bone remains and Escherichia coli. These DNA were amplified using human and bacterial specific primers. Using different blood, aged bone, and bacterial DNA dilutions along with PCR based methods; we checked their positive, negative effects, or detecting presence of inhibitors in aged bone DNA by PCR method. Our observation indicated that the addition of bacterial DNA could be a valid biological method for testing the quality of bone DNA to enable us to obtain a usable profile for the identification of human remains. This method will help to test the presence of inhibitors, quantity or even quality of DNA which are of importance in profiling archeological remains. Our method will help to determine if PCR failure is due to presence of inhibitors or lack of amplifiable DNA either because of degradation, minute amount or absence of human DNA.

  19. Negative effect of rapidly resorbing properties of bioactive glass-ceramics as bone graft substitute in a rabbit lumbar fusion model.

    Science.gov (United States)

    Lee, Jae Hyup; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Lee, Do-Yoon; Chang, Bong-Soon; Lee, Choon-Ki

    2014-03-01

    Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass-ceramics are resorbed before bony fusion.

  20. Rapid Formation of Supermassive Black Hole Binaries in Galaxy Mergers with Gas

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, L.; /Zurich U. /Zurich, ETH; Kazantzidis, S.; /KIPAC, Menlo Park; Madau, P.; /UC, Santa Cruz /Garching, Max Planck Inst.; Colpi, M.; /Milan Bicocca U.; Quinn, T.; /Washington U., Seattle; Wadsley, J.; /McMaster U.

    2008-03-24

    Supermassive black holes (SMBHs) are a ubiquitous component of the nuclei of galaxies. It is normally assumed that, following the merger of two massive galaxies, a SMBH binary will form, shrink due to stellar or gas dynamical processes and ultimately coalesce by emitting a burst of gravitational waves. However, so far it has not been possible to show how two SMBHs bind during a galaxy merger with gas due to the difficulty of modeling a wide range of spatial scales. Here we report hydrodynamical simulations that track the formation of a SMBH binary down to scales of a few light years following the collision between two spiral galaxies. A massive, turbulent nuclear gaseous disk arises as a result of the galaxy merger. The black holes form an eccentric binary in the disk in less than a million years as a result of the gravitational drag from the gas rather than from the stars.

  1. Ectopic bone formation as a complication of surgical rehabilitation in patients with Moebius' syndrome.

    Science.gov (United States)

    Franz, Marcus; Berndt, Alexander; Wehrhan, Falk; Schleier, Peter; Clement, Joachim; Hyckel, Peter

    2007-01-01

    Treatment of facial paralysis by muscular neurotization resulted in ectopic ossification in 1 of 134 cases in this department. That patient suffering from Moebius syndrome (MS) is presented. Reviewing the literature concerning MS, Hox genes and bone morphogenetic protein dysregulation, a pathogenesis of ossification in MS is suggested. The MS patient exhibited a congenital facial nerve palsy, which was treated by muscular neurotization (Lexer-Rosenthal). Because of postoperative ossification of scarred areas, osteotomy of the processus muscularis and mobilization of the masseter muscle was performed. Nevertheless, further ossification occurred at the interface between the mandible and zygoma and in two masticatory muscles. So, the construction of a neoarthrosis became necessary. Three years later, the iatrogenic bone defect had reossified despite of an active opening therapy. Ectopic ossification after muscular neurotization seems to be restricted to patients with MS and is triggered by trauma. Molecular pathogenesis: facial malformations in MS are caused by disturbances in embryonic patterning. Failure in the development of the second pharyngeal arch leads to a spatial BMP-4 dysregulation responsible for ossification after wounding of muscle fascia. Therefore, surgical rehabilitation of facial function by muscular neurotization is contra indicated in MS patients.

  2. Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation.

    Science.gov (United States)

    Tang, Yi; Weiss, Stephen J

    2017-03-04

    Snail and Slug are zinc-finger transcription factors that play key roles in directing the epithelial-mesenchymal transition (EMT) programs associated with normal development as well as disease progression. More recent work suggests that these EMT-associated transcription factors also modulate the function of both embryonic and adult stem cells. Interestingly, YAP and TAZ, the co-transcriptional effectors of the Hippo pathway, likewise play an important role in stem cell self-renewal and lineage commitment. While direct intersections between the Snail/Slug and Hippo pathways have not been described previously, we recently described an unexpected cooperative interaction between Snail/Slug and YAP/TAZ that controls the self-renewal and differentiation properties of bone marrow-derived mesenchymal stem cells (MSCs), a cell population critical to bone development. Additional studies revealed that both Snail and Slug are able to form binary complexes with either YAP or TAZ that, together, control YAP/TAZ transcriptional activity and function throughout mouse development. Given the more recent observations that MSC-like cell populations are found in association throughout the vasculature where they participate in tissue regeneration, fibrosis and cancer, the Snail/Slug-YAP/TAZ axis is well-positioned to regulate global stem cell function in health and disease.

  3. Fluoride’s Effects on the Formation of Teeth and Bones, and the Influence of Genetics

    Science.gov (United States)

    Everett, E.T.

    2011-01-01

    Fluorides are present in the environment. Excessive systemic exposure to fluorides can lead to disturbances of bone homeostasis (skeletal fluorosis) and enamel development (dental/enamel fluorosis). The severity of dental fluorosis is also dependent upon fluoride dose and the timing and duration of fluoride exposure. Fluoride’s actions on bone cells predominate as anabolic effects both in vitro and in vivo. More recently, fluoride has been shown to induce osteoclastogenesis in mice. Fluorides appear to mediate their actions through the MAPK signaling pathway and can lead to changes in gene expression, cell stress, and cell death. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride. Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations. Ultimately, this can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization. PMID:20929720

  4. Vesicle formation in the membrane of onion cells (Allium cepa) during rapid osmotic dehydration.

    Science.gov (United States)

    Assani, Akym; Moundanga, Sylvie; Beney, Laurent; Gervais, Patrick

    2009-12-01

    Optimization of osmotic dehydration in different plant cells has been investigated through the variation of parameters such as the nature of the sugar used, the concentration of osmotic solutions and the processing time. In micro-organisms such as the yeast, Saccharomyces cerevisiae, the exposure of a cell to a slow increase in osmotic pressure preserves cell viability after rehydration, while sudden dehydration involves a lower rate of cell viability, which could be due to membrane vesiculation. The aim of this work is to study cytoplasmic vesicle formation in onion epidermal cells (Allium cepa) as a function of the kinetics of osmotic pressure variation in the external medium. Onion epidermal cells were submitted either to an osmotic shock or to a progressive osmotic shift from an osmotic pressure of 2 to 24 MPa to induce plasmolysis. After 30 min in the treatment solution, deplasmolysis was carried out. Cells were observed by microscopy during the whole cycle of dehydration-rehydration. The application of an osmotic shock to onion cells, from an initial osmotic pressure of 2 MPa to a final one of 24 MPa for osmotic shift, from an initial osmotic pressure of 2 MPa to a final one of 24 MPa for 30 min, no vesicles were observed. Additionally, the absence of Hechtian strand connections led to the bursting of vesicles in the case of the osmotic shock. It is concluded that the kinetics of osmotic dehydration strongly influence vesicle formation in onion cells, and that Hechtian strand connections between protoplasts and exocytotic vesicles are a prerequisite for successful deplasmolysis. These results suggest that a decrease in the area-to-volume ratio of a cell could cause cell death following an osmotic shock.

  5. Multi-composite bioactive osteogenic sponges featuring mesenchymal stem cells, platelet-rich plasma, nanoporous silicon enclosures, and Peptide amphiphiles for rapid bone regeneration.

    Science.gov (United States)

    Murphy, Matthew B; Blashki, Daniel; Buchanan, Rachel M; Fan, Dongmei; De Rosa, Enrica; Shah, Ramille N; Stupp, Samuel I; Weiner, Bradley K; Simmons, Paul J; Ferrari, Mauro; Tasciotti, Ennio

    2011-06-21

    A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone) (PCL) scaffolds, platelet-rich plasma (PRP), BMP2-loaded nanoporous silicon enclosure (NSE) microparticles, mineralizing peptide amphiphiles (PA), and mesenchymal stem cells (MSC). Primary MSC from cortical bone (CB)  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM). Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.

  6. The Formation of Rapidly Rotating Black Holes in High-mass X-Ray Binaries

    Science.gov (United States)

    Batta, Aldo; Ramirez-Ruiz, Enrico; Fryer, Chris

    2017-09-01

    High-mass X-ray binaries (HMXRBs), such as Cygnus X-1, host some of the most rapidly spinning black holes (BHs) known to date, reaching spin parameters a≳ 0.84. However, there are several effects that can severely limit the maximum BH spin parameter that could be obtained from direct collapse, such as tidal synchronization, magnetic core-envelope coupling, and mass loss. Here, we propose an alternative scenario where the BH is produced by a failed supernova (SN) explosion that is unable to unbind the stellar progenitor. A large amount of fallback material ensues, whose interaction with the secondary naturally increases its overall angular momentum content, and therefore the spin of the BH when accreted. Through SPH hydrodynamic simulations, we studied the unsuccessful explosion of an 8 {M}⊙ pre-SN star in a close binary with a 12 {M}⊙ companion with an orbital period of ≈1.2 days, finding that it is possible to obtain a BH with a high spin parameter a≳ 0.8 even when the expected spin parameter from direct collapse is a≲ 0.3. This scenario also naturally explains the atmospheric metal pollution observed in HMXRB stellar companions.

  7. Rapid Single-step Formation of Liposomes by Flow Assisted Stationary Phase Interdiffusion.

    Science.gov (United States)

    Has, Chandra; Phapal, Sopan M; Sunthar, P

    2018-01-17

    Laboratory preparation of unilamellar liposomes often involves multiple steps carried out over several hours to achieve a monodisperse size distribution. Here we present a methodology, based on a recently introduced lipid self-assembly principle-stationary phase interdiffusion (SPI)-to prepare large unilamellar vesicles (LUVs) of a monodisperse population in a short period of about 10min. The stationary interface between a lipid-ethanol phase and an aqueous phase is created by a density difference induced convective flow in a horizontal capillary. The average size of the liposomes, as expected from the SPI principle, is modulated only by the temperature and the type of lipids. Lipid concentration, ethanol content, pH of the aqueous phase, and the time duration of the experiment have little influence on the mean diameter of the vesicles. This simple methodology can be easily carried out with a capillary and a micro-needled syringe, and provides a rapid production tool for researchers requiring reproducible liposome suspensions. Refined natural lipids, based on soy and egg lecithin mixtures, yield LUVs in the range 100-200 nm, suitable for drug delivery applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Runx2-I isoform contributes to fetal bone formation even in the absence of specific N-terminal amino acids.

    Directory of Open Access Journals (Sweden)

    Hideaki Okura

    Full Text Available The Runt-related transcription factor 2 (Runx2 gene encodes the transcription factor Runx2, which is the master regulator of osteoblast development; insufficiency of this protein causes disorders of bone development such as cleidocranial dysplasia. Runx2 has two isoforms, Runx2-II and Runx2-I, and production of each isoform is controlled by a unique promoter: a distal promoter (P1 and a proximal promoter (P2, respectively. Although several studies have focused on differences and similarities between the two Runx2 isoforms, their individual roles in bone formation have not yet been determined conclusively, partly because a Runx2-I-targeted mouse model is not available. In this study, we established a novel Runx2-manipulated mouse model in which the first ATG of Runx2-I was replaced with TGA (a stop codon, and a neomycin-resistant gene (neo cassette was inserted at the first intron of Runx2-I. Homozygous Runx2-Ineo/neo mice showed severely reduced expression of Runx2-I, whereas Runx2-II expression was largely retained. Runx2-Ineo/neo mice showed neonatal lethality, and in these mice, intramembranous ossification was more severely defective than endochondral ossification, presumably because of the greater involvement of Runx2-I, compared with that of Runx2-II in intramembranous ossification. Interestingly, the depletion of neo rescued the above-described phenotypes, indicating that the isoform-specific N-terminal region of Runx2-I is not functionally essential for bone development. Taken together, our results provide a novel clue leading to a better understanding of the roles of Runx2 isoforms in osteoblast development.

  9. Effect of a Particulate and a Putty-Like Tricalcium Phosphate-Based Bone-grafting Material on Bone Formation, Volume Stability and Osteogenic Marker Expression after Bilateral Sinus Floor Augmentation in Humans.

    Science.gov (United States)

    Knabe, Christine; Adel-Khattab, Doaa; Kluk, Esther; Struck, Rainer; Stiller, Michael

    2017-07-29

    This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. 10% autogenous bone chips were added to the grafting material during surgery. The grain size of the TCP granules was 700 to 1400 µm for TCP-G and 125 to 250 µm and 500 to 700 µm (ratio 1:1) for TCP-P. Biopsies were processed for immunohistochemical analysis of resin-embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the