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.......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...... formation and graft resorption in vivo. MATERIAL AND METHODS: Four harvesting techniques were used: (i) corticocancellous blocks particulated by a bone mill; (ii) bone scraper; (iii) piezosurgery; and (iv) bone slurry collected from a filter device upon drilling. The grafts were placed into bone defects...

The study of morphology and formation mechanism for tourmaline nodules of aplites from Khaku area (Hamedan with using fractal and three dimensional analysis

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Ali Asghar Sepahi-Gerow

2017-03-01

Full Text Available In aplites of Khaku area, located in the east of the Alvand body, tourmaline noduleswith spherical and dendritic shapes are dispersed. Some of these nodules have light halothat is actually a transition zone between the core of nodules and the host aplites.Geometrically, these nodules are fractal shapes. In these nodules fractal dimension vary from 1.46 in dendritic nodules to 1.92 in spherical nodules. In three-dimensionalreconstructions of the studied nodule, the average volume for the core is 34% and 66%for its margin. Based on evidences such as lack of veins between nodules, tourmalineswith anhedral forms, presence of a leucocratic halo in the aureole of some nodules, theirspherical shape, their linear and flow dispersion in the host rock these nodules have been crystallized in magmatic condition. In the final stages of magma crystallizationand the B content increment followed by beginning of unmixing in the melt, distinctspherical bubbles have been developed which gave rise to nodules formation. Magmaticsystem acts as chaotic systems and the presence of rotational and limited closed areas inthe vicinity of areas with disturbed paths has led to the formation of rounded anddendritic nodules beside each other.

A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts

DEFF Research Database (Denmark)

Henriksen, Kim; Andreassen, Kim V; Thudium, Christian S

2012-01-01

Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium wa...... dependent and independent of their resorptive activity, secrete factors stimulating osteoblastic bone formation.......Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium...... release. The osteoblastic cell line 2T3 was treated with 50% of CM or non-CM for 12days. Bone formation was assessed by Alizarin Red extraction. CM from mature osteoclasts induced bone formation, while CM from macrophages did not. Non-resorbing osteoclasts generated from osteopetrosis patients showed...

Heterotopic new bone formation causes resorption of the inductive bone matrix

International Nuclear Information System (INIS)

Nilsson, O.S.; Persson, P.E.; Ekelund, A.

1990-01-01

The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM

Dynamics of formation of ferromanganese nodules in the Indian Ocean

Digital Repository Service at National Institute of Oceanography (India)

Mukhopadhyay, R.; Ghosh, A.K.

., 2008). It is therefore interesting to examine and model the various factors that might influence the formation, growth and characters of nodules in the neighbouring sectors within the IONF (sector A to D, Fig. 2). The seafloor underlying... these sectors, originated from the Indian Ocean Ridge System (IORS), and is strikingly different from one sector to another. For example, the sectors A and C were formed during crustal stretching, and are characterised by a largely smooth seafloor...

Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts

International Nuclear Information System (INIS)

Utting, J.C.; Robins, S.P.; Brandao-Burch, A.; Orriss, I.R.; Behar, J.; Arnett, T.R.

2006-01-01

We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO 2 from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO 2 was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by 3 H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that collagen fibrils deposited by osteoblasts cultured in 2% O 2 were less organized and much less abundant than in 20% O 2 cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia

Nod factor supply under water stress conditions modulates cytokinin biosynthesis and enhances nodule formation and N nutrition in soybean.

Science.gov (United States)

Prudent, Marion; Salon, Christophe; Smith, Donald L; Emery, R J Neil

2016-09-01

Nod factors (NF) are molecules produced by rhizobia which are involved in the N 2 -fixing symbiosis with legume plants, enabling the formation of specific organs called nodules. Under drought conditions, nitrogen acquisition by N 2 -fixation is depressed, resulting in low legume productivity. In this study, we evaluated the effects of NF supply on nitrogen acquisition and on cytokinin biosynthesis of soybean plants grown under drought. NF supply to water stressed soybeans increased the CK content of all organs. The profile of CK metabolites also shifted from t-Z to cis-Z and an accumulation of nucleotide and glucoside conjugates. The changes in CK coincided with enhanced nodule formation with sustained nodule specific activity, which ultimately increased the total nitrogen fixed by the plant.

Atypical Localized Rheumatoid Nodule: Case Report

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KORHAN BARIS BAYRAM

2015-01-01

Full Text Available Rheumatoid nodules can be seen in about 30% of patiens with rheumatoid arthritis. They are occasionally localized subcutaneous, but they can rarely seen in visceral organs. Their appearance can be confused with many clinical conditions when they have atypical localizations. To exclude the presence of a malignancy, these lesions should always be investigated. We aimed to discuss a patient with rheumatoid nodule localized in close neighborhood of hyoid bone, presumed as malignancy.

Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

DEFF Research Database (Denmark)

Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

2011-01-01

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 f...

Observation of microscopic bone structure during bone formation. Application of micro-computed tomography for evaluation of bone quality

International Nuclear Information System (INIS)

Ueno, Takaaki; Yamamoto, Hiromitsu; Mizukawa, Nobuyoshi; Mishima, Katsuaki; Takagi, Shin; Sugahara, Toshio

1998-01-01

Bone formation in the autogenous periosteum of the tibia grafted to the floor of the mouth to bridge the mandible was studied by micro-CT to assess its efficacy in evaluating bone formation in rabbits. On soft radiographs, bone formation was observed from both ends of the periosteum on day 14. The bone increased in width and extended medially; contact was made in the center on day 28. The time course of the development of bone trabeculae was well demonstrated three-dimensionally on micro-CT. Indices of bone quality such as Tb-Th, Tb.N, and BV, which reflect the growth of trabeculae, increased gradually from days 14 to 21 and more rapidly from days 21 to 28, whereas Tb. S decreased gradually after grafting. The results suggest that micro-CT is useful in evaluating bone formation three-dimensionally. (author)

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...... volume measurements of the recovered grafts do not differentiate between viable and dead bone. We studied fresh syngeneic full-thickness bone grafts from calvaria, mandibula, tibia diaphysis, and iliac bone implanted in the back muscles of young Lewis rats. Bone formation in grafts recovered 3 weeks...... that the anatomical area of harvest is important regarding new bone formation in syngeneic bone grafts. However, the results do not support the contention that better maintenance of volume of calvarial grafts compared with iliac bone grafts is due to enhanced osteogenesis in the former....

Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

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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.

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....

[Nodulation competitiveness of nodule bacteria: Genetic control and adaptive significance].

Science.gov (United States)

Onishchuk, O P; Vorobyov, N I; Provorov, N A

2017-01-01

The most recent data on the system of cmp (competitiveness) genes that determine the nodulation competitiveness of rhizobial strains, i.e., the ability to compete for nodule formation in leguminous plants, is analyzed. Three genetic approaches for the construction of economically valuable strains of rhizobia are proposed: the amplification of positive regulators of competitiveness, the inactivation of the negative regulators of this trait, and the introduction of efficient competitiveness factors into strains capable of active nitrogen fixation.

Histological study on the new bone formation of the implanted bone allograft in sheep

International Nuclear Information System (INIS)

Li Youchen; Sun Guiying; Shi Zhancheng

1999-01-01

The purpose of this study is to compare the formation of new bone in the implanted frozen irradiated bone allograft with the fresh bone autograft. The work on animal model included resection and implantation of sheep's tibial diaphysis and intramedullary nail fixation, with total number 20. Tibias were harvested at 6, 12, and 24 months after operation. Sheep were fed with tetracycline I week before bone harvesting. Bones were examined with usual and fluorescence microscopes. The results showed that the progress of graft incorporation in allografts were generally similar to that of autografts. Capillaries penetration and callus formation extended from the host end to surround the host-graft junction in 6 months. Incorporation of new bone was nearly completed in 12 months; then the speed of new bone formation was decreased, and the implanted bone graft was almost completely substituted with non-nal bone structure in 24 months

Morphological assessment of bone mineralization in tibial metaphyses of ascorbic acid-deficient ODS rats.

Science.gov (United States)

Hasegawa, Tomoka; Li, Minqi; Hara, Kuniko; Sasaki, Muneteru; Tabata, Chihiro; de Freitas, Paulo Henrique Luiz; Hongo, Hiromi; Suzuki, Reiko; Kobayashi, Masatoshi; Inoue, Kiichiro; Yamamoto, Tsuneyuki; Oohata, Noboru; Oda, Kimimitsu; Akiyama, Yasuhiro; Amizuka, Norio

2011-08-01

Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.

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

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

Does simvastatin stimulate bone formation in vivo?

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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.

Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation

Energy Technology Data Exchange (ETDEWEB)

Severson, A.R. (Minnesota Univ., Duluth, MN (United States). Dept. of Anatomy and Cell Biology); Haut, C.F.; Firling, C.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biology); Huntley, T.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biochemistry and Molecular Biology)

1992-12-01

The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification. Thus, aluminum administration to rats appears to alter the differentiation and calcification of developing cartilage and bone in the DBM-induced bone formation model and suggests that aluminum by some mechanism alters the matrix calcification in growing bones. (orig.).

Leptin regulates bone formation via the sympathetic nervous system

Science.gov (United States)

Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

2002-01-01

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Functional Diversity of Fibroblast Growth Factors in Bone Formation

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Yuichiro Takei

2015-01-01

Full Text Available The functional significance of fibroblast growth factor (FGF signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs. Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.

Foliar application of pyraclostrobin fungicide enhances the growth, rhizobial-nodule formation and nitrogenase activity in soybean (var. JS-335).

Science.gov (United States)

Joshi, Juhie; Sharma, Sonika; Guruprasad, K N

2014-09-01

A field study was conducted to investigate the impact of the fungicide pyraclostrobin (F500 - Headline®; a.i. 20%) on the activity of nitrogenase in soybean (var. JS-335). Pyraclostrobin (F500) was applied on the leaves of soybean plants at 10 and 20 days after emergence (DAE) of seedlings at concentrations ranging from 0.05% to 1%. Leghemoglobin (Lb) content and nitrogenase activity in root nodules were analyzed at 45(th)day after emergence of seedlings indicated a remarkable increase in Lb content and enhanced activity of nitrogenase in the root nodules of pyraclostrobin treated plants. The fungicide also enhanced the number of nodules along with weight of nodules, root biomass and growth of shoot and leaves. Enhanced nitrogen fixation in the root nodules by pyraclostrobin improves the growth of the plant in soybean before flowering and pod formation which ultimately resulted in yield and yield attributes. These results suggest that pyraclostrobin (F500) can be successfully employed as a foliar spray under field conditions to enhance the growth, nitrogen assimilation and hence yield of soybean. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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......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...

Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation

NARCIS (Netherlands)

Croes, M.; Kruyt, M. C.; Groen, W. M.; Van Dorenmalen, K. M.A.; Dhert, W. J.A.; Öner, F. C.; Alblas, J.

2018-01-01

Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is

Organogenic nodule formation in hop: a tool to study morphogenesis in plants with biotechnological and medicinal applications.

Science.gov (United States)

Fortes, Ana M; Santos, Filipa; Pais, Maria S

2010-01-01

The usage of Humulus lupulus for brewing increased the demand for high-quality plant material. Simultaneously, hop has been used in traditional medicine and recently recognized with anticancer and anti-infective properties. Tissue culture techniques have been reported for a wide range of species, and open the prospect for propagation of disease-free, genetically uniform and massive amounts of plants in vitro. Moreover, the development of large-scale culture methods using bioreactors enables the industrial production of secondary metabolites. Reliable and efficient tissue culture protocol for shoot regeneration through organogenic nodule formation was established for hop. The present review describes the histological, and biochemical changes occurring during this morphogenic process, together with an analysis of transcriptional and metabolic profiles. We also discuss the existence of common molecular factors among three different morphogenic processes: organogenic nodules and somatic embryogenesis, which strictly speaking depend exclusively on intrinsic developmental reprogramming, and legume nitrogen-fixing root nodules, which arises in response to symbiosis. The review of the key factors that participate in hop nodule organogenesis and the comparison with other morphogenic processes may have merit as a study presenting recent advances in complex molecular networks occurring during morphogenesis and together, these provide a rich framework for biotechnology applications.

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

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

Science.gov (United States)

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Vibration acceleration promotes bone formation in rodent models.

Directory of Open Access Journals (Sweden)

Ryohei Uchida

Full Text Available 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

Glucocorticoids and inhibition of bone formation induced by skeletal unloading

International Nuclear Information System (INIS)

Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.

1988-01-01

Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

Interleukin-1beta-induced release of matrix proteins into culture media causes inhibition of mineralization of nodules formed by periodontal ligament cells in vitro.

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Chien, H H; Lin, W L; Cho, M I

1999-05-01

The mechanism by which interleukin-1beta (IL-1) inhibits the formation of mineralized tissue nodules by periodontal ligament (PDL) cells in vitro was investigated through the processes of morphological analysis, immunoprecipitation, and Northern blot analysis. PDL cells were obtained from a 2-day-old coagulum in tooth socket and cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bone serum (FBS) and antibiotics. Confluent cells were grown for up to 3 weeks in the presence of ascorbic acid (AA), beta-glycerophosphate (GP), and dexamethasone (Dex), or IL-1. PDL cells cultured in the presence of GP and AA did not differentiate, but those treated with Dex, GP, and AA (Dex group) underwent differentiation, showing four stages (confluent, multilayer, nodule, and mineralization) of disparate morphological characteristics. In contrast, the cells treated with IL-1, Dex, GP, and AA (IL-1 group) did form multilayers but failed to form mineralized nodules. Electron microscopy demonstrated that the Dex-induced mineralized nodules contain multilayers of fibroblastic cells, numerous collagen fibrils, and dense globular as well as fused electron dense patches that are associated with numerous apatite crystals. The nodule-like structures in the IL-1 group were also comprised of multilayered fibroblastic cells, but they contained only a small number of collagen fibrils, and no dense globular or fused patches. Von Kossa staining confirmed the presence of numerous mineralized nodules in the Dex group and their scarceness in the IL-1 group. Northern blot analysis of IL-1-treated cells, however, revealed the presence of mRNAs for type I collagen (Col I), secreted protein, acidic and rich in cysteine (SPARC), osteopontin (OPN), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), whose expression patterns and levels were comparable to those of the Dex group. Immunoprecipitation analysis of OPN and BSP in the cell/matrix layers and the culture

Rescuing loading induced bone formation at senescence.

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Sundar Srinivasan

2010-09-01

Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

Formation of blood clot on biomaterial implants influences bone healing.

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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.

Local induction of inflammation affects bone formation

NARCIS (Netherlands)

Croes, M; Kruyt, M C; Loozen, L; Kragten, A H; Yuan, H; Dhert, W J; Öner, F C; Alblas, J

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

Activation of cell divisions in legume nodulation

DEFF Research Database (Denmark)

Nadzieja, Marcin

organogenesis. Coordination of these two interdependent processes results in formation of nodules - bacterial accommodating structures where fixation of atmospheric nitrogen takes place. Plant hormones such as auxin and cytokinin play important roles in nodulation. In some legumes the infection process...... of auxin transport inhibitors or cytokinin alone was shown to induce cortical cell divisions in the absence of rhizobia in certain legume species. While the roles of auxin and cytokinin in nodulation have been studied extensively, the precise timing, location and means of molecular crosstalk between...

Radiostrontium clearance and bone formation in response to simulated internal screw fixation

International Nuclear Information System (INIS)

Daum, W.J.; Simmons, D.J.; Fenster, R.; Shively, R.A.

1987-01-01

Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling

Automatic Solitary Lung Nodule Detection in Computed Tomography Images Slices

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Sentana, I. W. B.; Jawas, N.; Asri, S. A.

2018-01-01

Lung nodule is an early indicator of some lung diseases, including lung cancer. In Computed Tomography (CT) based image, nodule is known as a shape that appears brighter than lung surrounding. This research aim to develop an application that automatically detect lung nodule in CT images. There are some steps in algorithm such as image acquisition and conversion, image binarization, lung segmentation, blob detection, and classification. Data acquisition is a step to taking image slice by slice from the original *.dicom format and then each image slices is converted into *.tif image format. Binarization that tailoring Otsu algorithm, than separated the background and foreground part of each image slices. After removing the background part, the next step is to segment part of the lung only so the nodule can localized easier. Once again Otsu algorithm is use to detect nodule blob in localized lung area. The final step is tailoring Support Vector Machine (SVM) to classify the nodule. The application has succeed detecting near round nodule with a certain threshold of size. Those detecting result shows drawback in part of thresholding size and shape of nodule that need to enhance in the next part of the research. The algorithm also cannot detect nodule that attached to wall and Lung Chanel, since it depend the searching only on colour differences.

Influence of demineralized bone matrix's embryonic origin on bone formation: an experimental study in rats.

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Stavropoulos, Andreas; Kostopoulos, Lambros; Mardas, Nicolaos; Karring, Thorkild

2003-01-01

There are results suggesting that differences regarding bone-inducing potential, in terms of amount and/or rate of bone formation, exist between demineralized bone matrices (DBMs) of different embryonic origins. The aim of the present study was to examine whether the embryonic origin of DBM affects bone formation when used as an adjunct to guided tissue regeneration (GTR). Endomembranous (EM) and endochondral (ECH) DBMs were produced from calvarial and long bones of rats, respectively. Prior to the study the osteoinductive properties of the DBMs were confirmed in six rats following intramuscular implantation. Following surgical exposure of the mandibular ramus, a rigid hemispheric Teflon capsule loosely packed with a standardized quantity of DBM was placed with its open part facing the lateral surface of the ramus in both sides of the jaw in 30 rats. In one side of the jaw, chosen at random, the capsule was filled with EM-DBM, whereas in the other side ECH-DBM was used. Groups of 10 animals were sacrificed after healing periods of 1, 2, and 4 months, and undecalcified sections of the capsules were produced and subjected to histologic analysis and computer-assisted planimetric measurements. During the experiment increasing amounts of newly formed bone were observed inside the capsules in both sides of the animals' jaws. Limited bone formation was observed in the 1- and 2-month specimens, but after 4 months of healing, the newly formed bone in the ECH-DBM grafted sides occupied 59.1% (range 45.6-74.7%) of the area created by the capsule versus 46.9% (range 23.0-64.0%) in the EM-DBM grafted sides (p =.01). It is concluded that the embryonic origin of DBM influences bone formation by GTR and that ECH-DBM is superior to EM-DBM.

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...

Bone marrow mesenchymal stem cells differentiation and proliferation on the surface of coral implant

International Nuclear Information System (INIS)

Al-Salihi, K.A.; Samsudin, A.R.

2004-01-01

This study was designed to evaluate the ability of natural coral implant to provide an environment for marrow cells to differentiate into osteoblasts and function suitable for mineralized tissue formation. DNA content, alkaline phosptatase (ALP) activity, calcium (Ca) content and mineralized nodules, were measured at day 3, day 7 and day 14, in rat bone marrow stromal cells cultured with coral discs glass discs, while cells alone and coral disc alone cultured as control. DNA content, ALP activity, Ca content measurements showed no difference between coral, glass and cells groups at 3 day which were higher than control (coral disc alone), but there were higher asurement at day 7 and 14 in the cell cultured on coral than on glass discs, control cells and control coral discs. Mineralized nodules formation (both in area and number) was more predominant on the coral surface than in control groups. These results showed that natural coral implant provided excellent and favorable situation for marrow cell to differentiate to osteoblasts, lead to large amount of mineralized tissue formation on coral surface. This in vitro result could explain the rapid bone bonding of coral in vivo. (Author)

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.

Nódulos linfóides medulares Bone marrow lymphoid nodules

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Silvia M. M. Magalhães

2003-06-01

Full Text Available A biópsia de medula óssea é parte integrante do estadiamento e seguimento de pacientes com doenças hematológicas. Nódulos linfóides são um achado comum, usualmente observados em associação com doenças inflamatórias crônicas, infecção, hemólise, síndromes mieloproliferativas e doenças auto-imunes. São, em geral, considerados reacionais. Sendo a medula óssea o sítio extranodal mais comumente envolvido nos linfomas foliculares, o diagnóstico diferencial mais importante é a infiltração medular por doença linfoproliferativa. Do ponto de vista prático, os infiltrados linfóides são, em geral, facilmente distinguíveis ao estudo histológico. Agregados reacionais são pequenos, têm bordas delimitadas, são compostos por uma população celular heterogênea e têm localização central. Nódulos malignos infiltram a medula óssea na região paratrabecular e são compostos por células clivadas. A análise imunofenotípica, utilizando um painel de anticorpos monoclonais, é capaz de definir a linhagem celular, subpopulação e estágio de diferenciação da população neoplásica, contribuindo para a confirmação do diagnóstico. Nos casos controversos, a análise molecular da proliferação linfóide pode ser útil. A monoclonalidade pode ser demonstrada pela restrição de cadeias leves ou através do rearranjo do DNA da cadeia pesada das imunoglobulinas. Idealmente, os resultados da análise molecular devem ser interpretados em conjunto com a análise morfológica e imunofenotípica. A morfologia continua sendo o padrão-ouro na avaliação da infiltração medular por linfoma folicular e as análises imunofenotípica e molecular devem ser consideradas complementares.Bone marrow trephine biopsies are an integral part of the diagnosis, staging and follow-up of patients with haematologic disorders. Lymphoid nodules are a common finding, usually reported in association with chronic inflammatory syndromes, infection

Low-intensity pulsed ultrasound enhances bone formation around miniscrew implants.

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Ganzorig, Khaliunaa; Kuroda, Shingo; Maeda, Yuichi; Mansjur, Karima; Sato, Minami; Nagata, Kumiko; Tanaka, Eiji

2015-06-01

Miniscrew implants (MSIs) are currently used to provide absolute anchorage in orthodontics; however, their initial stability is an issue of concern. Application of low-intensity pulsed ultrasound (LIPUS) can promote bone healing. Therefore, LIPUS application may stimulate bone formation around MSIs and enhance their initial stability. To investigate the effect of LIPUS exposure on bone formation after implantation of titanium (Ti) and stainless steel (SS) MSIs. MSIs made of Ti-6Al-4V and 316L SS were placed on rat tibiae and treated with LIPUS. The bone morphology around MSIs was evaluated by scanning electron microscopy and three-dimensional micro-computed tomography. MC3T3-E1 cells cultured on Ti and SS discs were treated with LIPUS, and the temporary expression of alkaline phosphatase (ALP) was examined. Bone-implant contact increased gradually from day 3 to day 14 after MSI insertion. LIPUS application increased the cortical bone density, cortical bone thickness, and cortical bone rate after implantation of Ti and SS MSIs (P<0.05). LIPUS exposure induced ALP upregulation in MC3T3-E1 cells at day 3 (P<0.05). LIPUS enhanced bone formation around Ti and SS MSIs, enhancing the initial stability of MSIs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fate of bone marrow stromal cells in a syngenic model of bone formation.

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Boukhechba, Florian; Balaguer, Thierry; Bouvet-Gerbettaz, Sébastien; Michiels, Jean-François; Bouler, Jean-Michel; Carle, Georges F; Scimeca, Jean-Claude; Rochet, Nathalie

2011-09-01

Bone marrow stromal cells (BMSCs) have been demonstrated to induce bone formation when associated to osteoconductive biomaterials and implanted in vivo. Nevertheless, their role in bone reconstruction is not fully understood and rare studies have been conducted to follow their destiny after implantation in syngenic models. The aim of the present work was to use sensitive and quantitative methods to track donor and recipient cells after implantation of BMSCs in a syngenic model of ectopic bone formation. Using polymerase chain reaction (PCR) amplification of the Sex determining Region Y (Sry) gene and in situ hybridization of the Y chromosome in parallel to histological analysis, we have quantified within the implants the survival of the donor cells and the colonization by the recipient cells. The putative migration of the BMSCs in peripheral organs was also analyzed. We show here that grafted cells do not survive more than 3 weeks after implantation and might migrate in peripheral lymphoid organs. These cells are responsible for the attraction of host cells within the implants, leading to the centripetal colonization of the biomaterial by new bone.

The aluminosilicate fraction of North Pacific manganese nodules

Science.gov (United States)

Bischoff, J.L.; Piper, D.Z.; Leong, K.

1981-01-01

Nine nodules collected from throughout the deep North Pacific were analyzed for their mineralogy and major-element composition before and after leaching with Chester-Hughes solution. Data indicate that the mineral phillipsite accounts for the major part (> 75%) of the aluminosilicate fraction of all nodules. It is suggested that formation of phillipsite takes place on growing nodule surfaces coupled with the oxidation of absorbed manganous ion. All the nodules could be described as ternary mixtures of amorphous iron fraction (Fe-Ti-P), manganese oxide fraction (Mn-Mg Cu-Ni), and phillipsite fraction (Al-Si-K-Na), these fractions accounting for 96% of the variability of the chemical composition. ?? 1981.

Evidence for the formation of different-sized nodules by different accretionary processes

Digital Repository Service at National Institute of Oceanography (India)

Valsangkar, A.B.; Karisiddaiah, S.M.

suggests that the smaller (M and I) nodules are diagenetic and the larger (S, B, L, and V) are hydrogenetic, exhibiting variations in todorokite abundance and in chemical composition. There is also substantial evidence that the nodules of high economic...

Nonlinear pattern formation in bone growth and architecture

Directory of Open Access Journals (Sweden)

Phil eSalmon

2015-01-01

Full Text Available The 3D morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatio-temporal 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 nonlinear 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 simulation of bone modeling.What insights has NPF provided to bone biology? One example concerns the genetic disorder Juvenile Pagets Disease (JPD 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 consequence of the

Formation of calcareous nodules in loess-paleosol sequences: Reviews of existing models with a proposed new "per evapotranspiration model"

Science.gov (United States)

Li, Yanrong; Zhang, Weiwei; Aydin, Adnan; Deng, Xiaohong

2018-04-01

Loess is a product of aeolian deposition during Quaternary glaciation cycles. Loess-paleosol sequences are rich in calcareous nodules (CNs). In the literature, two models are widely cited for the formation of CNs, namely "per descendum" and "per ascendum". However, there has been no direct testing or monitoring to support either of these contradictory models. This paper reviews a large number of multidisciplinary literature to evaluate the consistency, reliability and rationality of these two models. Three main conclusions are drawn: (1) the causative factors (variation of pH value along loess-paleosol sequence, decrease of CO2 partial pressure, and reduction of solvent water) that are used to support the per descendum model do not completely explain the supersaturation of infiltration solution with CaCO3, thereby making this model questionable; (2) the per ascendum model explains the formation of CNs along narrow horizons through upward evaporation; however, it fails to produce sporadic distributions and irregular shapes of nodules on loess slope faces and the frequent appearance of nodules around plant roots. In order to reconcile these deficiencies, we conducted an extensive field survey in various parts of Shanxi province. Based on this new set of observations, it was concluded that the "per ascendum" model can be extended to explain all occurrences of CNs. This extended model is called "per evapotranspiration".

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

Science.gov (United States)

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

International Nuclear Information System (INIS)

Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

2013-01-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

Science.gov (United States)

Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

2013-11-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

International Nuclear Information System (INIS)

Otsuru, Satoru; Tamai, Katsuto; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

2007-01-01

Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood

Spaceflight-induced vertebral bone loss in ovariectomized rats is associated with increased bone marrow adiposity and no change in bone formation

Science.gov (United States)

Keune, Jessica A; Philbrick, Kenneth A; Branscum, Adam J; Iwaniec, Urszula T; Turner, Russell T

2016-01-01

There is often a reciprocal relationship between bone marrow adipocytes and osteoblasts, suggesting that marrow adipose tissue (MAT) antagonizes osteoblast differentiation. MAT is increased in rodents during spaceflight but a causal relationship between MAT and bone loss remains unclear. In the present study, we evaluated the effects of a 14-day spaceflight on bone mass, bone resorption, bone formation, and MAT in lumbar vertebrae of ovariectomized (OVX) rats. Twelve-week-old OVX Fischer 344 rats were randomly assigned to a ground control or flight group. Following flight, histological sections of the second lumbar vertebrae (n=11/group) were stained using a technique that allowed simultaneous quantification of cells and preflight fluorochrome label. Compared with ground controls, rats flown in space had 32% lower cancellous bone area and 306% higher MAT. The increased adiposity was due to an increase in adipocyte number (224%) and size (26%). Mineral apposition rate and osteoblast turnover were unchanged during spaceflight. In contrast, resorption of a preflight fluorochrome and osteoclast-lined bone perimeter were increased (16% and 229%, respectively). The present findings indicate that cancellous bone loss in rat lumbar vertebrae during spaceflight is accompanied by increased bone resorption and MAT but no change in bone formation. These findings do not support the hypothesis that increased MAT during spaceflight reduces osteoblast activity or lifespan. However, in the context of ovarian hormone deficiency, bone formation during spaceflight was insufficient to balance increased resorption, indicating defective coupling. The results are therefore consistent with the hypothesis that during spaceflight mesenchymal stem cells are diverted to adipocytes at the expense of forming osteoblasts. PMID:28725730

[Endogenous pyrogen formation by bone marrow cells].

Science.gov (United States)

Efremov, O M; Sorokin, A V; El'kina, O A

1978-01-01

The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

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

2018-01-01

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

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

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

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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.

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

Science.gov (United States)

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin 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 beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

VsENOD5, VsENOD12 and VsENOD40 expression during Rhizobium-induced nodule formation on Vicia sativa roots

DEFF Research Database (Denmark)

Vijn, I; Yang, W C; Pallisgård, N

1995-01-01

We isolated ENOD5, ENOD12 and ENOD40 homologues from Vicia sativa and studied their expression pattern during Rhizobium-induced nodule formation. Comparison of the VsENOD40 nucleotide sequence with the pea, soybean and alfalfa ENOD40 sequences showed that the sequences contain two conserved regions...... the expression pattern of VsENOD5, VsENOD12 and VsENOD40 during Rhizobium-induced nodule formation. Although the expression of these genes is largely similar to that of the pea counterparts, differences where found for the expression of VsENOD12 and VsENOD40 in Vicia. VsENOD12 is expressed in the whole...... prefixation zone II, whereas in pea ENOD12 is only expressed in the distal part of this zone. VsENOD40 is expressed in the uninfected cells of interzone II-III, while in pea ENOD40 is expressed in both the uninfected and infected cells of this zone. Udgivelsesdato: 1995-Sep...

Trauma-induced heterotopic bone formation and the role of the immune system: A review.

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Kraft, Casey T; Agarwal, Shailesh; Ranganathan, Kavitha; Wong, Victor W; Loder, Shawn; Li, John; Delano, Matthew J; Levi, Benjamin

2016-01-01

Extremity trauma, spinal cord injuries, head injuries, and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities, and joint contractures. The immune system has been increasingly implicated in this debilitating condition. This review summarizes the various roles immune cells and inflammation play in the formation of ectopic bone and highlights potential areas of future investigation and treatment. Cell types in both the innate and adaptive immune system such as neutrophils, macrophages, mast cells, B cells, and T cells have all been implicated as having a role in ectopic bone formation through various mechanisms. Many of these cell types are promising areas of therapeutic investigation for potential treatment. The immune system has also been known to also influence osteoclastogenesis, which is heavily involved in ectopic bone formation. Chronic inflammation is also known to have an inhibitory role in the formation of ectopic bone, whereas acute inflammation is necessary for ectopic bone formation.

Late Effects of Heavy Ion Irradiation on Ex Vivo Osteoblastogenesis and Cancellous Bone Microarchitecture

Science.gov (United States)

Tran, Luan Hoang; Alwood, Joshua; Kumar, Akhilesh; Limoli, C. L.; Globus, Ruth

2012-01-01

Prolonged spaceflight causes degeneration of skeletal tissue with incomplete recovery even after return to Earth. We hypothesize that heavy ion irradiation, a component of Galactic Cosmic Radiation, damages osteoblast progenitors and may contribute to bone loss during long duration space travel beyond the protection of the Earth's magnetosphere. Male, 16 week old C57BL6/J mice were exposed to high LET (56 Fe, 600MeV) radiation using either low (5 or 10cGy) or high (50 or 200cGy) doses at the NASA Space Radiation Lab and were euthanized 3 - 4, 7, or 35 days later. Bone structure was quantified by microcomputed tomography (6.8 micron pixel size) and marrow cell redox assessed using membrane permeable, free radical sensitive fluorogenic dyes. To assess osteoblastogenesis, adherent marrow cells were cultured ex vivo, then mineralized nodule formation quantified by imaging and gene expression analyzed by RT PCR. Interestingly, 3 - 4 days post exposure, fluorogenic dyes that reflect cytoplasmic generation of reactive nitrogen/oxygen species (DAF FM Diacetate or CM H2DCFDA) revealed irradiation (50cGy) reduced free radical generation (20-45%) compared to sham irradiated controls. Alternatively, use of a dye showing relative specificity for mitochondrial superoxide generation (MitoSOX) revealed an 88% increase compared to controls. One week after exposure, reactive oxygen/nitrogen levels remained lower(24%) relative to sham irradiated controls. After one month, high dose irradiation (200 cGy) caused an 86% decrement in ex vivo nodule formation and a 16-31% decrement in bone volume to total volume and trabecular number (50, 200cGy) compared to controls. High dose irradiation (200cGy) up regulated expression of a late osteoblast marker (BGLAP) and select genes related to oxidative metabolism (Catalase) and DNA damage repair (Gadd45). In contrast, lower doses (5, 10cGy) did not affect bone structure or ex vivo nodule formation, but did down regulate iNOS by 0.54 - 0.58 fold

Callus formation in bone fractures combined with brain injury in rat

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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.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

Science.gov (United States)

Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

2016-01-01

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc.

Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone.

Science.gov (United States)

Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

2013-06-01

Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.

[Thyroid nodule].

Science.gov (United States)

Clerc, Jérôme

2005-01-31

The thyroid nodule is a frequent, most often benign, chronic, multifocal and slowly progressive disease. The first line strategy is to diagnose cancerous nodules (thyroid nodules is controversial since the prognosis of thyroid cancer is excellent for lesions measuring less than 20 mm. Though imaging accuracy is quite limited in assessing the diagnosis of thyroid cancer, both ultrasounds (US) and thyroid scan are helpful to enhance nodular identification (>30%), to sort the nodules relevant for cytological sampling and to optimize the follow-up, the major source of health costs. Suspicious and non contributive FNAs must have a control FNA within 6 months. Nodules with a non suspicious FNA (>85%) require long term follow-up. This follow-up is mainly morphological. New or evolutive nodules, as assessed by palpation or US, will require iterative FNAs or should be considered for surgery. In patients with hyperfunctioning nodules on the scan (10 to 20%), a yearly evaluation of the TSH level is sufficient. These nodules account either for autonomously functioning ones, which slowly develop towards thyrotoxicosis, or for hyperplastic nodules frequently disclosing a lymphocytic thyroiditis. Morbidity due to thyroid autonomy is still underestimated especially in aging patients with TSH levels thyroid nodule is suggested.

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

Science.gov (United States)

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

Science.gov (United States)

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

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

In vitro study on bone formation and surface topography from the standpoint of biomechanics.

Science.gov (United States)

Kawahara, H; Soeda, Y; Niwa, K; Takahashi, M; Kawahara, D; Araki, N

2004-12-01

Effect of surface topography upon cell-adhesion, -orientation and -differentiation was investigated by in vitro study on cellular responses to titanium substratum with different surface roughness. Cell-shape, -function and -differentiation depending upon the surface topography were clarified by use of bone formative group cells (BFGCs) derived from bone marrow of beagle's femur. BFGCs consisted of hematopoietic stem cells (HSC) and osteogenetic stem cells (OSC). Cell differentiation of BFGCs was expressed and promoted by structural changes of cytoskeleton, and cell-organella, which was caused by mechanical stress with cytoplasmic stretching of cell adhesions to the substratum. Phagocytic monocytes of HSC differentiated to osteomediator cells (OMC) by cytoplasmic stretching with cell adhesion to the substratum. The OMC mediated and promoted cell differentiation from OSC to osteoblast through osteoblastic phenotype cell (OBC) by cell-aggregation of nodules with "pile up" phenomenon of OBC onto OMC. The osteogenesis might be performed by coupling work of both cells, OMC originated from monocyte of HSC and OBC originated from OSC, which were explained by SEM, TEM and fluorescent probe investigation on BFGCs on the test plate of cp titanium plates with different topographies. This osteogenetic process was proved by investigating cell proliferation, DNA contents, cell-adhesion, alkaline phosphatase activity and osteocalcine productivity for cells on the titanium plates with different topographies. The study showed increased osteogenic effects for cells cultured on Ti with increased surface roughness. Possible mechanisms were discussed from a biomechanical perspective.

Evaluation of radiographic imaging techniques in lung nodule detection

International Nuclear Information System (INIS)

Ho, J.T.; Kruger, R.A.

1989-01-01

Dual-energy radiography appears to be the most effective technique to address bone superposition that compromises conventional chest radiography. A dual-energy, single-exposure, film-based technique was compared with a dual-energy, dual-exposure technique and conventional chest radiography in a simulated lung nodule detection study. Observers detected more nodules on images produced by dual-energy techniques than on images produced by conventional chest radiography. The difference between dual-energy and conventional chest radiography is statistically significant and the difference between dual-energy, dual-exposure and single-exposure techniques is statistically insignificant. The single-exposure technique has the potential to replace the dual-exposure technique in future clinical application

Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

Science.gov (United States)

Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

2010-01-01

Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.

[Painless skin nodules and ecchymosis in a school-aged girl].

Science.gov (United States)

Liu, Ying-Ting; Yang, Ming-Hua; Cao, Li-Zhi; Huang, Ye-Hong; Xie, Min; Yang, Liang-Chun; Yang, Hui; Tang, Xing

2015-10-01

A 7-year-old girl was admitted to Xiangya Hospital due to systemic lymphadenectasis for 2 months and skin ecchymosis for 3 days. Nine months ago, the girl experienced painless nodules in the left lower extremity with no apparent causes. Three months later, dermatorrhagia and ecchymosis occurred in many regions such as the periocular areas, conjunctiva, oral mucosa, perineal area, and groin, with a "raccoon sign" in both eyes; superficial lymphadenectasis and hepatosplenomegaly were also observed in many regions. The pathological sections for the skin nodules showed malignant tumors in lymphohematopoietic cells, and in combination with clinical manifestations, immunohistochemistry, and positive results for CD4, CD56, and CD123 by bone marrow flow cytometry, the girl was diagnosed with blastic plasmacytoid dendritic cell neoplasm. Then high-risk ALL regimen was applied as the chemotherapy for this girl. At present, the girl has been followed up for 3 months; ecchymosis has disappeared, and the enlarged lymph nodes have shrunk. No abnormal cells have been found in bone marrow morphological examination, and bone marrow flow cytometry has shown that primitive precursor cells account for 1.5% and express CD33, CD34, CD123, and CD117.

Effect of exogenous application of rhizopine on lucerne root nodulation

African Journals Online (AJOL)

Rhizopine, 3-0 -methyl scyllo-inosamine was applied to the roots of luceme seedling inoculated with either rhizopine synthesizing Sinorhizobium meliloti strain L530 or the non-rhizopine synthesizing strain Rm 1021 . There was an initial delay in nodule formation. A significant increase in the number of nodules formed in ...

cell- and tissue-specific transcriptome analyses of Medicago truncatula root nodules.

Directory of Open Access Journals (Sweden)

Erik Limpens

Full Text Available Legumes have the unique ability to host nitrogen-fixing Rhizobium bacteria as symbiosomes inside root nodule cells. To get insight into this key process, which forms the heart of the endosymbiosis, we isolated specific cells/tissues at different stages of symbiosome formation from nodules of the model legume Medicago truncatula using laser-capture microdissection. Next, we determined their associated expression profiles using Affymetrix Medicago GeneChips. Cells were collected from the nodule infection zone divided into a distal (where symbiosome formation and division occur and proximal region (where symbiosomes are mainly differentiating, as well as infected cells from the fixation zone containing mature nitrogen fixing symbiosomes. As non-infected cells/tissue we included nodule meristem cells and uninfected cells from the fixation zone. Here, we present a comprehensive gene expression map of an indeterminate Medicago nodule and selected genes that show specific enriched expression in the different cells or tissues. Validation of the obtained expression profiles, by comparison to published gene expression profiles and experimental verification, indicates that the data can be used as digital "in situ". This digital "in situ" offers a genome-wide insight into genes specifically associated with subsequent stages of symbiosome and nodule cell development, and can serve to guide future functional studies.

Marginal zinc deficiency in pregnant rats impairs bone matrix formation and bone mineralization in their neonates.

Science.gov (United States)

Nagata, Masashi; Kayanoma, Megumu; Takahashi, Takeshi; Kaneko, Tetsuo; Hara, Hiroshi

2011-08-01

Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups and fed AIN-93G-based experimental diets containing 35 mg Zn/kg (Zn adequately supplied, N) or 7 mg Zn/kg (low level of Zn, L) from 14-day preconception to 20 days of gestation, that is, 1 day before normal delivery. Neonates were delivered by cesarean section. Litter size and neonate weight were not different between the two groups. However, in the L-diet-fed dam group, bone matrix formation in isolated neonatal calvaria culture was clearly impaired and was not recovered by the addition of Zn into the culture media. Additionally, serum concentration of osteocalcin, as a bone formation parameter, was lower in neonates from the L-diet-fed dam group. Impaired bone mineralization was observed with a significantly lower content of phosphorus in neonate femurs from L-diet-fed dams compared with those from N-diet-fed dams. Moreover, Zn content in the femur and calvaria of neonates from the L-diet group was lower than that of the N-diet-fed group. In the marginally Zn-deficient dams, femoral Zn content, serum concentrations of Zn, and osteocalcin were reduced when compared with control dams. We conclude that maternal Zn deficiency causes impairment of bone matrix formation and bone mineralization in neonates, implying the importance of Zn intake during pregnancy for proper bone development of offspring.

Nodules size: An important factor in nodule mining?

Digital Repository Service at National Institute of Oceanography (India)

Valsangkar, A.B.

A study of about 850 different sized nodules from 234 sites in the Central Indian Basin (CIB) showed a clear inverse relationship between size and grade of nodules. Among the different sized nodules, only the small (less than 2 cm) and medium (2...

Pharmacotherapy for thyroid nodules. A systematic review and meta-analysis.

Science.gov (United States)

Richter, Bernd; Neises, Gudrun; Clar, Christine

2002-09-01

The review highlights the uncertainty in the management of nodular thyroid disease. Thyroxine suppressive treatment is given in the hope that nodules might decrease in size, sometimes assuming that dependency on TSH is different in benign and malignant nodular disease. Follow-up of benign nodules over 10 years suggested that most remain the same, shrink, or disappear [14]. TSH suppression may lead to hyperthyroidism, reduced bone density [37.39], and atrial fibrilation; however, apart from reduction of nodule size or arrest in nodule growth, thyroxine therapy may benefit patients by reducing perinodular volume. Consequently, both pressure symptoms and cosmetic complaints could improve. Unfortunately, no information concerning symptoms or well-being is available from published randomized trials. In conclusion, more high quality studies of sufficient duration with adequate power estimation are needed. Uncertainty about predictors of response or the impact on outcomes that are important to patients leaves considerable doubt about the wisdom of applying suppressive therapy. Future studies shoudl include patient-important outcomes including thyroid cancer incidence, health-related quality of life and costs.

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

International Nuclear Information System (INIS)

Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

2013-01-01

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 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 and

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F FDG PET/CT and 99mTc HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

International Nuclear Information System (INIS)

Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun

2011-01-01

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent 99mT c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

Radiologic study of the experimentally produced bone destruction and bone formation

International Nuclear Information System (INIS)

Chei, Soon Chul; Ahn, Hyung Kyu

1988-01-01

Bone destruction was induced experimentally by the insertion of a bit of the arsenic compound into the pulp chambers of the right premolars and the artificial bone defects were produced in the periapical regions of the left premolars in 7 dogs. The serial standardized periapical radiographs using aluminum stepwedge attached to the XCP instruments and resin bite blocks were taken following insertion of arsenic compound and at 2, 4, 7, 10, 14, 17, 21, 24 and 28 days in case of bone destruction and following bone injury and weekly thereafter for a total of 14 weeks in case of bone formation . The errors of the method were determined with error estimators described by the Duinkerke. All radiographs were evaluated by the visual examination after joint evaluation by three dental radiologists and analysed with densitometer. The following results were obtained; 1. Analysis of the bone destruction process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.04 mm, S.D. for the over-all error; 0.06 mm, S.D. for the positioning error; 0.05 mm) 2) The radiographic changes were observed after 7 days in 6 cases, 4 days in 1 case and 10 days in 1 case by the visual examination. 3) Aluminum equivalent values were diminished after 2 days and the diminution of 0.58 ± 0.19 mm was demanded to be detected by the visual examination. 2. Analysis of the bone formation process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.03 mm, S.D. for the over-all error; 0.04 mm, S.D. for the positioning error; 0.04 mm) 2) The radiographic changes were observed after 2 weeks in 5 cases and 3 weeks in 2 cases by the visual examination. 3) Aluminum equivalent values were increased after 1 week and the increase of 0.45 ± 0.15 mm was demanded to be detected by the visual examination. 4) Aluminum equivalent values were increased continuously for 7 or 9 weeks but there was only extremely small

Bone induction by surface-double-modified true bone ceramics in vitro and in vivo

International Nuclear Information System (INIS)

Li, Jingfeng; Chen, Liaobin; Deng, Yu; Zheng, Qixin; Guo, Xiaodong; Zou, Zhenwei; Liu, Yudong; Lan, Shenghui

2013-01-01

True bone ceramic (TBC), obtained by twice sintering fresh bovine cancellous bone at high temperatures, is an osteoconductive and bioactive bone substitute material that exhibits excellent biocompatibility with hard tissue. The authors have previously synthesized a novel BMP-2-related peptide, P24, and found that it could enhance the osteoblastic differentiation of cells. The objective of the present study was to construct a double-modified TBC via mineralization into simulated body fluid and P24 incorporation for enhanced bone formation. In vitro experiments revealed that surface mineralization-modified (SMM) TBC scaffolds demonstrated efficiency for sustained release of P24. The P24/SMM-TBC composite exhibited increased osteogenic activity by cell adhesion rate determination, MTT assay, alkaline phosphatase staining, and calcium nodule staining with alizarin red compared with SMM-TBC and TBC. In vivo studies showed that the P24/SMM-TBC composite scaffold promoted significant bone defect repair, in marked contrast to stand-alone SMM-TBC and TBC, based on the results of radiographic evaluation and histological examination. These findings indicate that SMM-TBC is a good scaffold for the controlled release of P24 and that the P24/SMM-TBC composite could improve the adhesion, proliferation and differentiation of cells and repair bone defects. The double-modified P24/SMM-TBC composite biomaterial shows potential for clinical application in bone tissue engineering. (paper)

Thyroid nodule

International Nuclear Information System (INIS)

McKenney, J.F.

1975-01-01

A palpable mass or nodule may represent any one of a large and diverse group of conditions that involve the thyroid. Whether the patient is euthyroid, hypothyroid, or hyperthyroid can be assessed, and the cause of hypofunction or hyperfunction can usually be determined. Scintiscanning provides important information on the anatomic structure of thyroid nodules. A hot nodule should be ablated by either radioiodine or surgery. A warm nodule usually responds to suppression therapy; if regression does not occur, the problem should be reevaluated. A cold nodule should be surgically excised, as microscopic study of such a lesion is mandatory

Lung nodule detection by microdose CT versus chest radiography (standard and dual-energy subtracted).

Science.gov (United States)

Ebner, Lukas; Bütikofer, Yanik; Ott, Daniel; Huber, Adrian; Landau, Julia; Roos, Justus E; Heverhagen, Johannes T; Christe, Andreas

2015-04-01

The purpose of this study was to investigate the feasibility of microdose CT using a comparable dose as for conventional chest radiographs in two planes including dual-energy subtraction for lung nodule assessment. We investigated 65 chest phantoms with 141 lung nodules, using an anthropomorphic chest phantom with artificial lung nodules. Microdose CT parameters were 80 kV and 6 mAs, with pitch of 2.2. Iterative reconstruction algorithms and an integrated circuit detector system (Stellar, Siemens Healthcare) were applied for maximum dose reduction. Maximum intensity projections (MIPs) were reconstructed. Chest radiographs were acquired in two projections with bone suppression. Four blinded radiologists interpreted the images in random order. A soft-tissue CT kernel (I30f) delivered better sensitivities in a pilot study than a hard kernel (I70f), with respective mean (SD) sensitivities of 91.1%±2.2% versus 85.6%±5.6% (p=0.041). Nodule size was measured accurately for all kernels. Mean clustered nodule sensitivity with chest radiography was 45.7%±8.1% (with bone suppression, 46.1%±8%; p=0.94); for microdose CT, nodule sensitivity was 83.6%±9% without MIP (with additional MIP, 92.5%±6%; pmicrodose CT for readers 1, 2, 3, and 4 were 84.3%, 90.7%, 68.6%, and 45.0%, respectively. Sensitivities with chest radiography for readers 1, 2, 3, and 4 were 42.9%, 58.6%, 36.4%, and 90.7%, respectively. In the per-phantom analysis, respective sensitivities of microdose CT versus chest radiography were 96.2% and 75% (pmicrodose CT, the applied dose was 0.1323 mSv. Microdose CT is better than the combination of chest radiography and dual-energy subtraction for the detection of solid nodules between 5 and 12 mm at a lower dose level of 0.13 mSv. Soft-tissue kernels allow better sensitivities. These preliminary results indicate that microdose CT has the potential to replace conventional chest radiography for lung nodule detection.

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.

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 prostaglandin...... treatment. Histologic examination of tubular bones showed hyperostosis presumably due to prostaglandin-induced rapid formation of primitive bone. The additional finding of extensive resorption of the outer cortical surface and bone formation at the inner surface suggested a reversible phase after...

Gut microbiota induce IGF-1 and promote bone formation and growth

Science.gov (United States)

Yan, Jing; Herzog, Jeremy W.; Tsang, Kelly; Brennan, Caitlin A.; Bower, Maureen A.; Garrett, Wendy S.; Sartor, Balfour R.; Charles, Julia F.

2016-01-01

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth. PMID:27821775

Understanding coupling between bone resorption and formation

DEFF Research Database (Denmark)

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

2013-01-01

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...

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.

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

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

International Nuclear Information System (INIS)

Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

2011-01-01

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

Science.gov (United States)

de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

2015-04-01

Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

Science.gov (United States)

Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

Proteome reference maps of the Lotus japonicus nodule and root

DEFF Research Database (Denmark)

Dam, Svend Secher; Dyrlund, Thomas F.; Ussatjuk, Anna

2014-01-01

formation mutant (snf1) was determined. From nodules and roots, 780 and 790 protein spots from 2D gels were identified and approximately 45% of the corresponding unique gene accessions were common. Including a previous proteomics set from Lotus pod and seed, the common gene accessions were decreased to 7...... stress level at this developmental stage. In contrast, protein spots corresponding to nodulins such as leghemoglobin, asparagine synthetase, sucrose synthase, and glutamine synthetase were prevalent in red nodules. The distinct biochemical state of nodules was further highlighted by the conspicuous...

Early nodulins in root nodule development

NARCIS (Netherlands)

Scheres, B.

1990-01-01

The symbiotic interaction between bacteria of the genus Rhizobium and leguminous plants leads to the formation of root nodules, which are specific nitrogen-fixing organs on the roots of plants. Bacteria enter the root by infection threads, and concomitantly cell

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 Sintered hydroxyapatites induce bone formation in adult baboons via intrinsic osteoinductivity regulated by the geometry of the substratum. Bone is thereby formed without exogenous bone morphogenetic proteins (BMPs), well-characterized inducers...

Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover.

Science.gov (United States)

Hussein, H; Dulin, J; Smanik, L; Drost, W T; Russell, D; Wellman, M; Bertone, A

2017-08-01

Our investigations evaluated the effect of VEL-0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX-1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis of plasma bone biomarkers (CTX-1 and osteocalcin), poststudy bone fluorescent labeling, and bone biopsy were performed. Bone specimens were further processed for microcomputed tomography and bone histomorphometry. Each dose of this CatKI transiently inhibited plasma CTX-1 (reflecting inhibition of bone collagen resorption) and increased bone plasma osteocalcin concentrations, with no detectable adverse effect on normal bone turnover in the face of exercise. Bone morphology, density, and formation rate were not different between control and treated group. Further investigation of CatK inhibition in abnormal bone turnover is required in animals with bone diseases. © 2016 John Wiley & Sons Ltd.

Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

Directory of Open Access Journals (Sweden)

J O Eniwumide

2007-08-01

Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

Proteomic insights into intra- and intercellular plant-bacteria symbiotic association during root nodule formation

Directory of Open Access Journals (Sweden)

Afshin eSalavati

2013-02-01

Full Text Available Over the last several decades, there have been a large number of studies done on the all aspects of legumes and bacteria which participate in nitrogen-fixing symbiosis. The analysis of legume-bacteria interaction is not just a matter of numerical complexity in terms of variants of gene products that can arise from a single gene. Bacteria regulate their quorum-sensing genes to enhance their ability to induce conjugation of plasmids and symbiotic islands, and various protein secretion mechanisms; that can stimulate a collection of chain reactions including species-specific combinations of plant-secretion isoflavonoids, complicated calcium signaling pathways and autoregulation of nodulation mechanisms. Quorum-sensing systems are introduced by the intra- and intercellular organization of gene products lead to protein–protein interactions or targeting of proteins to specific cellular structures. In this study, an attempt has been made to review significant contributions related to nodule formation and development and their impacts on cell proteome for better understanding of plant-bacterium interaction mechanism at protein level. This review would not only provide new insights into the plant-bacteria symbiosis response mechanisms but would also highlights the importance of studying changes in protein abundance inside and outside of cells in response to symbiosis. Furthermore, the application to agriculture programe of plant-bacteria interaction will be discussed.

Multi-protein delivery by nanodiamonds promotes bone formation.

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Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

2013-11-01

Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.

Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells

International Nuclear Information System (INIS)

Tu Qisheng; Valverde, Paloma; Chen, Jake

2006-01-01

Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of α1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively

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

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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.

Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

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Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

2012-03-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

Effects of Different Reconstruction Parameters on CT Volumetric Measurement 
of Pulmonary Nodules

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Rongrong YANG

2012-02-01

Full Text Available Background and objective It has been proven that volumetric measurements could detect subtle changes in small pulmonary nodules in serial CT scans, and thus may play an important role in the follow-up of indeterminate pulmonary nodules and in differentiating malignant nodules from benign nodules. The current study aims to evaluate the effects of different reconstruction parameters on the volumetric measurements of pulmonary nodules in chest CT scans. Methods Thirty subjects who underwent chest CT scan because of indeterminate pulmonary nodules in General Hospital of Tianjin Medical University from December 2009 to August 2011 were retrospectively analyzed. A total of 52 pulmonary nodules were included, and all CT data were reconstructed using three reconstruction algorithms and three slice thicknesses. The volumetric measurements of the nodules were performed using the advanced lung analysis (ALA software. The effects of the reconstruction algorithms, slice thicknesses, and nodule diameters on the volumetric measurements were assessed using the multivariate analysis of variance for repeated measures, the correlation analysis, and the Bland-Altman method. Results The reconstruction algorithms (F=13.6, P<0.001 and slice thicknesses (F=4.4, P=0.02 had significant effects on the measured volume of pulmonary nodules. In addition, the coefficients of variation of nine measurements were inversely related with nodule diameter (r=-0.814, P<0.001. The volume measured at the 2.5 mm slice thickness had poor agreement with the volumes measured at 1.25 mm and 0.625 mm, respectively. Moreover, the best agreement was achieved between the slice thicknesses of 1.25 mm and 0.625 mm using the bone algorithm. Conclusion Reconstruction algorithms and slice thicknesses have significant impacts on the volumetric measurements of lung nodules, especially for the small nodules. Therefore, the reconstruction setting in serial CT scans should be consistent in the follow

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

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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.

[Experimental study of the effect of new bone formation on new type artificial bone composed of bioactive ceramics].

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Zhu, Minghua; Zeng, Yi; Sun, Tao; Peng, Qiang

2005-03-15

To investigate the osteogenic potential of four kinds of new bioactive ceramics combined with bovine bone morphogenetic proteins (BMP) and to explore the feasibility of using compounds as bone substitute material. Ninety-six rats were divided into 4 groups (24 in each group). BMP was combined with hydroxyapatite (HA), tricalcium phosphate (TCP), fluoridated-HA (FHA), and collagen-HA(CHA) respectively. The left thighs of the rats implanted with HA/BMP, TCP/BMP, FHA/BMP, and CHA/BMP were used as experimental groups. The right thighs of the rats implanted with HA, TCP, CHA, and decalcified dentin matrix (DDM) were used as control groups. The rats were sacrificed 1, 3, 5 and 7 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP), phosphorus (P), and total protein (TP) measurement. The histological observation and electronic microscope scanning of the implants were also made. The cartilage growth in the 4 experimental groups and the control group implanted with DDM was observed 1 week after operation and fibrous connective tissues were observed in the other 3 control groups. 3 weeks after implantation, lamellar bone with bone marrow and positive reaction in ALP stain were observed in the 4 experimental groups. No bone formation or positive reaction in ALP stain were observed in the control groups. The amount of ALP activity, P value, and new bone formation in the experimental groups were higher than those in the control group(P < 0.05). The amount of ALP activity, P value, and new bone formation in TCP/BMP group were higher than those in HA/BMP, CHA/BMP and FHA/BMP groups (P < 0.05). There was no significant difference in TP between the BMP treatment group and the control groups. From 5th to 7th week, new bone formation, histochemistry evaluation, and the level of ALP, P, TP value were as high as those in the 3rd week. New composite artificial bone of TCP/BMP, HA/BMP, CHA/BMP, and FHA/BMP all prove to be effective, but TCP/BMP is the

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

International Nuclear Information System (INIS)

Choi, Eui Hwan; Kim, Su Gwan

1999-01-01

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.

Automated lung nodule classification following automated nodule detection on CT: A serial approach

International Nuclear Information System (INIS)

Armato, Samuel G. III; Altman, Michael B.; Wilkie, Joel; Sone, Shusuke; Li, Feng; Doi, Kunio; Roy, Arunabha S.

2003-01-01

We have evaluated the performance of an automated classifier applied to the task of differentiating malignant and benign lung nodules in low-dose helical computed tomography (CT) scans acquired as part of a lung cancer screening program. The nodules classified in this manner were initially identified by our automated lung nodule detection method, so that the output of automated lung nodule detection was used as input to automated lung nodule classification. This study begins to narrow the distinction between the 'detection task' and the 'classification task'. Automated lung nodule detection is based on two- and three-dimensional analyses of the CT image data. Gray-level-thresholding techniques are used to identify initial lung nodule candidates, for which morphological and gray-level features are computed. A rule-based approach is applied to reduce the number of nodule candidates that correspond to non-nodules, and the features of remaining candidates are merged through linear discriminant analysis to obtain final detection results. Automated lung nodule classification merges the features of the lung nodule candidates identified by the detection algorithm that correspond to actual nodules through another linear discriminant classifier to distinguish between malignant and benign nodules. The automated classification method was applied to the computerized detection results obtained from a database of 393 low-dose thoracic CT scans containing 470 confirmed lung nodules (69 malignant and 401 benign nodules). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the classifier to differentiate between nodule candidates that correspond to malignant nodules and nodule candidates that correspond to benign lesions. The area under the ROC curve for this classification task attained a value of 0.79 during a leave-one-out evaluation

Early nodule senescence is activated in symbiotic mutants of pea (Pisum sativum L.) forming ineffective nodules blocked at different nodule developmental stages.

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Serova, Tatiana A; Tsyganova, Anna V; Tsyganov, Viktor E

2018-04-03

Plant symbiotic mutants are useful tool to uncover the molecular-genetic mechanisms of nodule senescence. The pea (Pisum sativum L.) mutants SGEFix - -1 (sym40), SGEFix - -3 (sym26), and SGEFix - -7 (sym27) display an early nodule senescence phenotype, whereas the mutant SGEFix - -2 (sym33) does not show premature degradation of symbiotic structures, but its nodules show an enhanced immune response. The nodules of these mutants were compared with each other and with those of the wild-type SGE line using seven marker genes that are known to be activated during nodule senescence. In wild-type SGE nodules, transcript levels of all of the senescence-associated genes were highest at 6 weeks after inoculation (WAI). The senescence-associated genes showed higher transcript abundance in mutant nodules than in wild-type nodules at 2 WAI and attained maximum levels in the mutant nodules at 4 WAI. Immunolocalization analyses showed that the ethylene precursor 1-aminocyclopropane-1-carboxylate accumulated earlier in the mutant nodules than in wild-type nodules. Together, these results showed that nodule senescence was activated in ineffective nodules blocked at different developmental stages in pea lines that harbor mutations in four symbiotic genes.

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

Competitive Advantage Provided by Bacterial Motility in the Formation of Nodules by Rhizobium meliloti

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Ames, Peter; Bergman, Kostia

1981-01-01

The effect of motility on the competitive success of Rhizobium meliloti in nodule production was investigated. A motile strain formed more nodules than expected when mixed at various unfavorable ratios with either flagellated or nonflagellated nonmotile derivatives. We conclude that motility confers a selective advantage on rhizobia when competing with nonmotile strains. PMID:7298580

[Biocompatibility of poly-L-lactic acid/Bioglass-guided bone regeneration membranes processed with oxygen plasma].

Science.gov (United States)

Fang, Wei; Zeng, Shu-Guang; Gao, Wen-Feng

2015-04-01

To prepare and characterize a nano-scale fibrous hydrophilic poly-L-lactic acid/ Bioglass (PLLA/BG) composite membrane and evaluate its biocompatibility as a composite membrane for guiding bone regeneration (GBR). PLLA/BG-guided bone regeneration membrane was treated by oxygen plasma to improved its hydrophilicity. The growth of MG-63 osteoblasts on the membrane was observed using Hoechst fluorescence staining, and the biocompatibility of the membrane was evaluated by calculating the cells adhesion rate and proliferation rate. Osteogenesis of MG-63 cells was assessed by detecting alkaline phosphatase (ALP), and the formation of calcified nodules and cell morphology changes were observed using scanning electron microscope (SEM). The cell adhesion rates of PLLA/BG-guided bone regeneration membrane treated with oxygen plasma were (30.570±0.96)%, (47.27±0.78)%, and (66.78±0.69)% at 1, 3, and 6 h, respectively, significantly higher than those on PLLA membrane and untreated PLLA/BG membrane (Pmembranes increased with time, but highest on oxygen plasma-treated PLLA/BG membrane (Pplasma treatment of the PLLA/BG membrane promoted cell adhesion. The membranes with Bioglass promoted the matrix secretion of the osteoblasts. Under SEM, the formation of calcified nodules and spindle-shaped cell morphology were observed on oxygen plasma-treated PLLA/BG membrane. Oxygen plasma-treated PLLA/BG composite membrane has good biocompatibility and can promote adhesion, proliferation and osteogenesis of the osteoblasts.

Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis

International Nuclear Information System (INIS)

Santos, Vitorino Modesto dos; Lima, Marcus Aurelho de; Marinho, Euripedes Oliveira; Marinho, Marco Aurelio de Oliveira; Santos, Lister Arruda Modesto dos; Raphael, Cristiane Mendes

2000-01-01

A case of parasitic thyroid nodule is presented. The patient was a non symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid trauma or surgery, she presented a 1.6 x 0.7 x 0.5 cm right pre-laryngeal lymph node-like mass which, on ultrasonography, appeared distinct from the gland. TSH, thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated and T4-free level was normal. Thyroid and total body 99m Tc isonitrile scintiscan showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle aspiration of the nodule showed epithelial cells with nuclear atypia and oncocitic changes plus intense lymphoid infiltration and germinative center formation, simulating lymph node metastasis of papillary thyroid carcinoma. Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic thyroiditis. Parasitic thyroid nodule must always be remembered so that unnecessary surgical assessment and undesirable sequels may be avoided. (author)

Enhancement of bone formation in rabbits by recombinant human growth hormone

International Nuclear Information System (INIS)

Ehrnberg, A.; Brosjoe, O.; Laaftman, P.; Nilsson, O.; Stroemberg, L.

1993-01-01

We studied the effect of human recombinant growth hormone on diaphyseal bone in 40 adult rabbits. The diaphyseal periosteum of one femur in each animal was mechanically stimulated by a nylon cerclage band. The bands induced an increase in bone formation, bone mineral content, and maximum torque capacity of the diaphyseal bone at 1 and 2 months. Growth hormone enhanced the anabolic effect of the cerclage bands on bone metabolism, evidenced by a further increase in torsional strength of the femurs. (au) (32 refs.)

Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

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Mathilde Doyard

Full Text Available Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation

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Md. Abdullah Al Mamun

Full Text Available BACKGROUND: Tridaxprocumbens flavonoids (TPFs are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2 CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using {sup 18F} FDG PET/CT and {sup 99mT}c HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

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Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

2011-09-15

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent {sup 99mT}c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

The relationship between inflammation and new bone formation in patients with ankylosing spondylitis

OpenAIRE

Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

2008-01-01

Introduction Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Methods Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondyl...

Diffuse Anterior Retinoblastoma with Sarcoidosis-Like Nodule

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Koji Kitazawa

2015-12-01

Full Text Available Background: Retinoblastomas account for 4% of malignancies in children, 1-2% of which are diffuse infiltrating retinoblastomas. Diffuse anterior retinoblastoma is rare and does not involve the retina. Here, we report on a diffuse anterior retinoblastoma with large sarcoidosis-like nodules on the iris that were responsive to anti-inflammatory therapy. Case: We present a 6-year-old girl who had anterior uveitis with white nodules on the iris and posterior surface of the cornea in her right eye. The nodules initially responded well to anti-inflammatory treatment. However, anterior segment optical coherence tomography (AS-OCT showed that the nodules gradually grew, shrinking the iris. We then collected the aqueous humor for diagnosis. A biopsy revealed clusters of small cells with a high nuclear-to-cytoplasm ratio with partial rosette formation. Therefore, we diagnosed diffuse anterior retinoblastoma without retinal involvement and performed enucleation of the right eye. The histopathology demonstrated undifferentiated cells similar to those seen on the biopsy, and tumor cells invaded the iris stroma, posterior surface of the cornea, ciliary body, and sclera. After the enucleation, she underwent chemotherapy and remains alive. Conclusion: A differential diagnosis of retinoblastoma should be considered when white nodules refractory to anti-inflammatory therapy occur in the eye, even in the absence of obvious retinal masses. AS-OCT findings are useful in assessing retinoblastoma.

Functionalized Surface Geometries Induce: “Bone: Formation by Autoinduction”

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Ugo Ripamonti

2018-02-01

Full Text Available The induction of tissue formation, and the allied disciplines of tissue engineering and regenerative medicine, have flooded the twenty-first century tissue biology scenario and morphed into high expectations of a fulfilling regenerative dream of molecularly generated tissues and organs in assembling human tissue factories. The grand conceptualization of deploying soluble molecular signals, first defined by Turing as forms generating substances, or morphogens, stemmed from classic last century studies that hypothesized the presence of morphogens in several mineralized and non-mineralized mammalian matrices. The realization of morphogens within mammalian matrices devised dissociative extractions and chromatographic procedures to isolate, purify, and finally reconstitute the cloned morphogens, found to be members of the transforming growth factor-β (TGF-β supergene family, with insoluble signals or substrata to induce de novo tissue induction and morphogenesis. Can we however construct macroporous bioreactors per se capable of inducing bone formation even without the exogenous applications of the osteogenic soluble molecular signals of the TGF-β supergene family? This review describes original research on coral-derived calcium phosphate-based macroporous constructs showing that the formation of bone is independent of the exogenous application of the osteogenic soluble signals of the TGF-β supergene family. Such signals are the molecular bases of the induction of bone formation. The aim of this review is to primarily describe today's hottest topic of biomaterials' science, i.e., to construct and define osteogenetic biomaterials' surfaces that per se, in its own right, do initiate the induction of bone formation. Biomaterials are often used to reconstruct osseous defects particularly in the craniofacial skeleton. Edentulism did spring titanium implants as tooth replacement strategies. No were else that titanium surfaces require functionalized

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

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Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

2016-08-24

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. Copyright © 2016, American Association for the Advancement of Science.

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

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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.

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. ...

Deep learning aided decision support for pulmonary nodules diagnosing: a review.

Science.gov (United States)

Yang, Yixin; Feng, Xiaoyi; Chi, Wenhao; Li, Zhengyang; Duan, Wenzhe; Liu, Haiping; Liang, Wenhua; Wang, Wei; Chen, Ping; He, Jianxing; Liu, Bo

2018-04-01

Deep learning techniques have recently emerged as promising decision supporting approaches to automatically analyze medical images for different clinical diagnosing purposes. Diagnosing of pulmonary nodules by using computer-assisted diagnosing has received considerable theoretical, computational, and empirical research work, and considerable methods have been developed for detection and classification of pulmonary nodules on different formats of images including chest radiographs, computed tomography (CT), and positron emission tomography in the past five decades. The recent remarkable and significant progress in deep learning for pulmonary nodules achieved in both academia and the industry has demonstrated that deep learning techniques seem to be promising alternative decision support schemes to effectively tackle the central issues in pulmonary nodules diagnosing, including feature extraction, nodule detection, false-positive reduction, and benign-malignant classification for the huge volume of chest scan data. The main goal of this investigation is to provide a comprehensive state-of-the-art review of the deep learning aided decision support for pulmonary nodules diagnosing. As far as the authors know, this is the first time that a review is devoted exclusively to deep learning techniques for pulmonary nodules diagnosing.

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

Science.gov (United States)

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

Skin metastasis from conventional giant cell tumor of bone: conceptual significance

International Nuclear Information System (INIS)

Tyler, W.; Barrett, T.; Frassica, F.; McCarthy, E.

2002-01-01

A conventional giant cell tumor of the proximal femur recurred twice locally and developed pulmonary nodules. The lung lesions were felt to be an example of ''benign'' metastases. Eight months after the initial presentation, the patient developed a single skin nodule on the contralateral leg. Histologic features of the skin nodule showed conventional giant cell tumor identical to the bone lesion. This nodule is a manifestation of arterial metastasis typical of any malignant tumor and seemingly contradicts the concept of ''benign '' metastasis. (orig.)

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

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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.

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

, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION......Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... 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...

The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

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Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

1985-01-01

The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

Root nodule symbiosis in Lotus japonicus drives the establishment of distinctive rhizosphere, root, and nodule bacterial communities.

Science.gov (United States)

Zgadzaj, Rafal; Garrido-Oter, Ruben; Jensen, Dorthe Bodker; Koprivova, Anna; Schulze-Lefert, Paul; Radutoiu, Simona

2016-12-06

Lotus japonicus has been used for decades as a model legume to study the establishment of binary symbiotic relationships with nitrogen-fixing rhizobia that trigger root nodule organogenesis for bacterial accommodation. Using community profiling of 16S rRNA gene amplicons, we reveal that in Lotus, distinctive nodule- and root-inhabiting communities are established by parallel, rather than consecutive, selection of bacteria from the rhizosphere and root compartments. Comparative analyses of wild-type (WT) and symbiotic mutants in Nod factor receptor5 (nfr5), Nodule inception (nin) and Lotus histidine kinase1 (lhk1) genes identified a previously unsuspected role of the nodulation pathway in the establishment of different bacterial assemblages in the root and rhizosphere. We found that the loss of nitrogen-fixing symbiosis dramatically alters community structure in the latter two compartments, affecting at least 14 bacterial orders. The differential plant growth phenotypes seen between WT and the symbiotic mutants in nonsupplemented soil were retained under nitrogen-supplemented conditions that blocked the formation of functional nodules in WT, whereas the symbiosis-impaired mutants maintain an altered community structure in the nitrogen-supplemented soil. This finding provides strong evidence that the root-associated community shift in the symbiotic mutants is a direct consequence of the disabled symbiosis pathway rather than an indirect effect resulting from abolished symbiotic nitrogen fixation. Our findings imply a role of the legume host in selecting a broad taxonomic range of root-associated bacteria that, in addition to rhizobia, likely contribute to plant growth and ecological performance.

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.

Tissue-engineered bone formation using human bone marrow stromal cells and novel β-tricalcium phosphate

International Nuclear Information System (INIS)

Liu Guangpeng; Zhao Li; Cui Lei; Liu Wei; Cao Yilin

2007-01-01

In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel β-tricalcium phosphate (β-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous β-TCP scaffolds with pores of 300-500 μm in size were prepared by the polymeric sponge method. β-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous β-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In β-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in β-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous β-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering

Tissue-engineered bone formation using human bone marrow stromal cells and novel {beta}-tricalcium phosphate

Energy Technology Data Exchange (ETDEWEB)

Liu Guangpeng [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Zhao Li [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cui Lei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Liu Wei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cao Yilin [National Tissue Engineering Research and Development Center, Shanghai 200235 (China)

2007-06-01

In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel {beta}-tricalcium phosphate ({beta}-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous {beta}-TCP scaffolds with pores of 300-500 {mu}m in size were prepared by the polymeric sponge method. {beta}-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous {beta}-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In {beta}-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in {beta}-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous {beta}-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering.

The Use of Injectable Chitosan/Nanohydroxyapatite/Collagen Composites with Bone Marrow Mesenchymal Stem Cells to Promote Ectopic Bone Formation In Vivo

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Bo Yu

2013-01-01

Full Text Available The aim of this study was to evaluate ectopic in vivo bone formation with or without rat bone mesenchymal stem cells (rBMSCs of an injectable Chitosan/Nanohydroxyapatite/Collagen (CS/nHAC composite. The CS/nHAC composites were injected subcutaneously into the backs of Wistar rats with freshly loaded rBMSCs at a density of 10×106 cells/mL, and the CS/nHAC composites without cells were used as negative controls. New bone formation, degradation of composites, and degree of calcification were evaluated by Computed Tomography (CT and three-dimensional (3D CT reconstruction. Histological evaluations were performed to further assess bone structure and extracellular matrix by HE and Masson staining. The inflammatory reactions related to osteogenesis were also investigated in the present study. In comparison with the CS/nHAC composites, this study revealed that CS/nHAC/rBMSCs composites showed relatively higher percentage of calcification, better establishment of ECM, and less degradation rate. Meanwhile, different extents of inflammatory reactions were also observed in the CS/nHAC and CS/nHAC/rBMSCs explants at 2 and 4 weeks after implantation. Altogether, CS/nHAC/rBMSCs composites are superior to CS/nHAC composites in ectopic bone formation. In conclusion, the rBMSCs-seeded CS/nHAC composites may be beneficial to enhancing ectopic bone formation in vivo.

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation.

Science.gov (United States)

Winkler, I G; Pettit, A R; Raggatt, L J; Jacobsen, R N; Forristal, C E; Barbier, V; Nowlan, B; Cisterne, A; Bendall, L J; Sims, N A; Lévesque, J-P

2012-07-01

The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

Science.gov (United States)

Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

2013-05-01

During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

Computer-aided detection of pulmonary nodules: influence of nodule characteristics on detection performance

International Nuclear Information System (INIS)

Marten, K.; Engelke, C.; Seyfarth, T.; Grillhoesl, A.; Obenauer, S.; Rummeny, E.J.

2005-01-01

AIM: To evaluate prospectively the influence of pulmonary nodule characteristics on detection performances of a computer-aided diagnosis (CAD) tool and experienced chest radiologists using multislice CT (MSCT). MATERIALS AND METHODS: MSCT scans of 20 consecutive patients were evaluated by a CAD system and two independent chest radiologists for presence of pulmonary nodules. Nodule size, position, margin, matrix characteristics, vascular and pleural attachments and reader confidence were recorded and data compared with an independent standard of reference. Statistical analysis for predictors influencing nodule detection or reader performance included chi-squared, retrograde stepwise conditional logistic regression with odds ratios and nodule detection proportion estimates (DPE), and ROC analysis. RESULTS: For 135 nodules, detection rates for CAD and readers were 76.3, 52.6 and 52.6%, respectively; false-positive rates were 0.55, 0.25 and 0.15 per examination, respectively. In consensus with CAD the reader detection rate increased to 93.3%, and the false-positive rate dropped to 0.1/scan. DPEs for nodules ≤5 mm were significantly higher for ICAD than for the readers (p<0.05). Absence of vascular attachment was the only significant predictor of nodule detection by CAD (p=0.0006-0.008). There were no predictors of nodule detection for reader consensus with CAD. In contrast, vascular attachment predicted nodule detection by the readers (p=0.0001-0.003). Reader sensitivity was higher for nodules with vascular attachment than for unattached nodules (sensitivities 0.768 and 0.369; 95% confidence intervals=0.651-0.861 and 0.253-0.498, respectively). CONCLUSION: CAD increases nodule detection rates, decreases false-positive rates and compensates for deficient reader performance in detection of smallest lesions and of nodules without vascular attachment

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

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

African Journals Online (AJOL)

were compared. Conclusion: Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing. Key words: Bio‑stimulation, laser, rapid maxillary expansion. Date of Acceptance: 12‑Jan‑2015. Address for correspondence: Dr. M Demirkol,.

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

In vivo assessment of bone formation (osteogenesis) potential by isolated cells is an important method for analysis of cells and factors control ling bone formation. Currently, cell implantation mixed with hydroxyapa-tite/tricalcium phosphate in an open system (subcutaneous implantation) in immun...

Assessment of activated porous granules on implant fixation and early bone formation in sheep

Directory of Open Access Journals (Sweden)

Ming Ding

2016-04-01

Conclusion: In conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.

3-D Analysis of Graphite Nodules in Ductile Cast Iron Using FIB-SEM

DEFF Research Database (Denmark)

D'Angelo, Luca; Jespersen, Freja N.; MacDonald, A. Nicole

Ductile cast iron samples were analysed in a Focused Ion Beam Scanning Electron Microscope, FIB-SEM. The focussed ion beam was used to carefully remove layers of the graphite nodules to reveal internal structures in the nodules. The sample preparation and milling procedure for sectioning graphite...... inside the nodules, their orientation in relation to the graphite and the chemistry of the inclusions is analysed and described. Formation of the structures during solidification and subsequent cooling to room temperature is discussed....

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.

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep

DEFF Research Database (Denmark)

Ding, Ming; Snoek Henriksen, Susan; Martinetti, Roberta

2017-01-01

allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while......, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016....

Evaluating the Bone Tissue Regeneration Capability of the Chinese Herbal Decoction Danggui Buxue Tang from a Molecular Biology Perspective

Directory of Open Access Journals (Sweden)

Wen-Ling Wang

2014-01-01

Full Text Available Large bone defects are a considerable challenge to reconstructive surgeons. Numerous traditional Chinese herbal medicines have been used to repair and regenerate bone tissue. This study investigated the bone regeneration potential of Danggui Buxue Tang (DBT, a Chinese herbal decoction prepared from Radix Astragali (RA and Radix Angelicae Sinensis (RAS, from a molecular biology perspective. The optimal ratio of RA and RAS used in DBT for osteoblast culture was obtained by colorimetric and alkaline phosphatase (ALP activity assays. Moreover, the optimal concentration of DBT for bone cell culture was also determined by colorimetric, ALP activity, nodule formation, Western blotting, wound-healing, and tartrate-resistant acid phosphatase activity assays. Consequently, the most appropriate weight ratio of RA to RAS for the proliferation and differentiation of osteoblasts was 5 : 1. Moreover, the most effective concentration of DBT was 1,000 μg/mL, which significantly increased the number of osteoblasts, intracellular ALP levels, and nodule numbers, while inhibiting osteoclast activity. Additionally, 1,000 μg/mL of DBT was able to stimulate p-ERK and p-JNK signal pathway. Therefore, DBT is highly promising for use in accelerating fracture healing in the middle or late healing periods.

Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration.

Science.gov (United States)

Spalthoff, S; Jehn, P; Zimmerer, R; Möllmann, U; Gellrich, N-C; Kokemueller, H

2015-06-01

We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Piezoelectricity could predict sites of formation/resorption in bone remodelling and modelling.

Science.gov (United States)

Fernández, J R; García-Aznar, J M; Martínez, R

2012-01-07

We have developed a mathematical approach for modelling the piezoelectric behaviour of bone tissue in order to evaluate the electrical surface charges in bone under different mechanical conditions. This model is able to explain how bones change their curvature, where osteoblasts or osteoclasts could detect in the periosteal/endosteal surfaces the different electrical charges promoting bone formation or resorption. This mechanism also allows to understand the BMU progression in function of the electro-mechanical bone behaviour. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detection of pulmonary nodules on lung X-ray images. Studies on multi-resolutional filter and energy subtraction images

International Nuclear Information System (INIS)

Sawada, Akira; Sato, Yoshinobu; Kido, Shoji; Tamura, Shinichi

1999-01-01

The purpose of this work is to prove the effectiveness of an energy subtraction image for the detection of pulmonary nodules and the effectiveness of multi-resolutional filter on an energy subtraction image to detect pulmonary nodules. Also we study influential factors to the accuracy of detection of pulmonary nodules from viewpoints of types of images, types of digital filters and types of evaluation methods. As one type of images, we select an energy subtraction image, which removes bones such as ribs from the conventional X-ray image by utilizing the difference of X-ray absorption ratios at different energy between bones and soft tissue. Ribs and vessels are major causes of CAD errors in detection of pulmonary nodules and many researches have tried to solve this problem. So we select conventional X-ray images and energy subtraction X-ray images as types of images, and at the same time select ∇ 2 G (Laplacian of Guassian) filter, Min-DD (Minimum Directional Difference) filter and our multi-resolutional filter as types of digital filters. Also we select two evaluation methods and prove the effectiveness of an energy subtraction image, the effectiveness of Min-DD filter on a conventional X-ray image and the effectiveness of multi-resolutional filter on an energy subtraction image. (author)

Digital tomosynthesis for evaluating metastatic lung nodules: nodule visibility, learning curves, and reading times.

Science.gov (United States)

Lee, Kyung Hee; Goo, Jin Mo; Lee, Sang Min; Park, Chang Min; Bahn, Young Eun; Kim, Hyungjin; Song, Yong Sub; Hwang, Eui Jin

2015-01-01

To evaluate nodule visibility, learning curves, and reading times for digital tomosynthesis (DT). We included 80 patients who underwent computed tomography (CT) and DT before pulmonary metastasectomy. One experienced chest radiologist annotated all visible nodules on thin-section CT scans using computer-aided detection software. Two radiologists used CT as the reference standard and retrospectively graded the visibility of nodules on DT. Nodule detection performance was evaluated in four sessions of 20 cases each by six readers. After each session, readers were unblinded to the DT images by revealing the true-positive markings and were instructed to self-analyze their own misreads. Receiver-operating-characteristic curves were determined. Among 414 nodules on CT, 53.3% (221/414) were visible on DT. The main reason for not seeing a nodule on DT was small size (93.3%, ≤ 5 mm). DT revealed a substantial number of malignant nodules (84.1%, 143/170). The proportion of malignant nodules among visible nodules on DT was significantly higher (64.7%, 143/221) than that on CT (41.1%, 170/414) (p 0.8, and the average detection rate for malignant nodules was 85% (210/246). The inter-session analysis of the AUC showed no significant differences among the readers, and the detection rate for malignant nodules did not differ across sessions. A slight improvement in reading times was observed. Most malignant nodules > 5 mm were visible on DT. As nodule detection performance was high from the initial session, DT may be readily applicable for radiology residents and board-certified radiologists.

Bone formation within a breast abscess

OpenAIRE

Mannu, Gurdeep Singh; Ahmed, Farid; Cunnick, Giles; Mungalsingh, Naren

2014-01-01

We present a rare case of osseous metaplasia in a poorly healing breast abscess. An 87-year-old woman was referred to the breast surgery clinic with a painful lump in her right breast. Initial imaging and core biopsy suggested a breast abscess. Despite several courses of antibiotics and repeated attempts at aspiration the painful lesion persisted. It was eventually surgically excised in its entirety and final histopathology showed the presence of bone formation within the abscess. The patient...

Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations.

Science.gov (United States)

Zuscik, Michael J; Ma, Lin; Buckley, Taylor; Puzas, J Edward; Drissi, Hicham; Schwarz, Edward M; O'Keefe, Regis J

2007-09-01

It has been established that skeletal growth is stunted in lead-exposed children. Because chondrogenesis is a seminal step during skeletal development, elucidating the impact of Pb on this process is the first step toward understanding the mechanism of Pb toxicity in the skeleton. The aim of this study was to test the hypothesis that Pb alters chondrogenic commitment of mesenchymal cells and to assess the effects of Pb on various signaling pathways. We assessed the influence of Pb on chondrogenesis in murine limb bud mesenchymal cells (MSCs) using nodule formation assays and gene analyses. The effects of Pb on transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signaling was studied using luciferase-based reporters and Western analyses, and luciferase-based assays were used to study cyclic adenosine monophosphate response element binding protein (CREB), beta-catenin, AP-1, and nuclear factor-kappa B (NF-kappaB) signaling. We also used an ectopic bone formation assay to determine how Pb affects chondrogenesis in vivo. Pb-exposed MSCs showed enhanced basal and TGF-beta/BMP induction of chondrogenesis, evidenced by enhanced nodule formation and up-regulation of Sox-9, type 2 collagen, and aggrecan, all key markers of chondrogenesis. We observed enhanced chondrogenesis during ectopic bone formation in mice preexposed to Pb via drinking water. In MSCs, Pb enhanced TGF-beta but inhibited BMP-2 signaling, as measured by luciferase reporter assays and Western analyses of Smad phosphorylation. Although Pb had no effect on basal CREB or Wnt/beta-catenin pathway activity, it induced NFkappaB signaling and inhibited AP-1 signaling. The in vitro and in vivo induction of chondrogenesis by Pb likely involves modulation and integration of multiple signaling pathways including TGF-beta, BMP, AP-1, and NFkappaB.

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.

Directory of Open Access Journals (Sweden)

Liao Wang

Full Text Available Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA sintered at 1200°C and two biphasic calcium phosphate (BCP ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate, sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model.

Age-related new bone formation following the use of cancellous bone-block allografts for reconstruction of atrophic alveolar ridges.

Science.gov (United States)

Nissan, Joseph; Kolerman, Roni; Chaushu, Liat; Vered, Marilena; Naishlos, Sarit; Chaushu, Gavriel

2018-02-01

An age-related decrease in the number of osteogenic progenitor cells may compromise bone augmentation. Histomorphometrical assessment of age-related new bone formation, following atrophic alveolar ridge reconstruction, using cancellous bone-block allografts. Ninety-three consecutive patients (58 females and 35 males) were referred for implant-supported restoration of 122 severe atrophic alveolar ridges. Alveolar ridge deficiency locations were classified as anterior maxilla (n = 58), posterior maxilla (n= 32), and posterior mandible (n = 32). A bony deficiency of at least 3 mm horizontally and up to 3 mm vertically according to computerized tomography (CT) in the posterior mandible and anterior maxilla, served as inclusion criteria. In the posterior maxilla, a residual alveolar ridge up to 4 mm vertically according to CT served as inclusion criteria. Augmentation was performed by the use of cancellous bone-block allografts. Bone biopsies (9-month posterior maxilla, 4 months anterior maxilla and posterior mandible) of young (≤40 years) versus older (>40 years) patients were histomorphometrically evaluated. In the posterior maxilla, no statistically significant histomorphometric differences were noted. While at the anterior maxilla and posterior mandible, statistically significant more newly formed bone was found in young versus older individuals, respectively (38.6% vs 19.8%, P = 0.04 and 69% vs 31%, P = .05). New bone formation following residual alveolar ridge bone grafting is age-related. Longer bone consolidation and healing time may be recommended for older individuals. © 2017 Wiley Periodicals, Inc.

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

Science.gov (United States)

Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

2003-06-13

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

Interstitial laser photocoagulation for benign thyroid nodules: time to treat large nodules.

Science.gov (United States)

Amabile, Gerardo; Rotondi, Mario; Pirali, Barbara; Dionisio, Rosa; Agozzino, Lucio; Lanza, Michele; Buonanno, Luciano; Di Filippo, Bruno; Fonte, Rodolfo; Chiovato, Luca

2011-09-01

Interstitial laser photocoagulation (ILP) is a new therapeutic option for the ablation of non-functioning and hyper-functioning benign thyroid nodules. Amelioration of the ablation procedure currently allows treating large nodules. Aim of this study was to evaluate the therapeutic efficacy of ILP, performed according to a modified protocol of ablation, in patients with large functioning and non-functioning thyroid nodules and to identify the best parameters for predicting successful outcome in hyperthyroid patients. Fifty-one patients with non-functioning thyroid nodules (group 1) and 26 patients with hyperfunctioning thyroid nodules (group 2) were enrolled. All patients had a nodular volume ≥40 ml. Patients were addressed to 1-3 cycles of ILP. A cycle consisted of three ILP sessions, each lasting 5-10 minutes repeated at an interval of 1 month. After each cycle of ILP patients underwent thyroid evaluation. A nodule volume reduction, expressed as percentage of the basal volume, significantly occurred in both groups (F = 190.4; P nodule volume; (iii) total amount of energy delivered expressed in Joule. ROC curves identified the percentage of volume reduction as the best parameter predicting a normalized serum TSH (area under the curve 0.962; P thyroid nodules, both in terms of nodule size reduction and cure of hyperthyroidism (87% of cured patients after the last ILP cycle). ILP should not be limited to patients refusing or being ineligible for surgery and/or radioiodine. Copyright © 2011 Wiley-Liss, Inc.

Digital tomosynthesis for evaluating metastatic lung nodules: Nodule visibility, learning curves, and reading times

International Nuclear Information System (INIS)

Lee, Kyung Hee; Goo, Jin Mo; Lee, Sang Min; Park, Chang Min; Bahn, Young Eun; Kim, Hyung Jin; Song, Yong Sub; Hwang, Eui Jin

2015-01-01

To evaluate nodule visibility, learning curves, and reading times for digital tomosynthesis (DT). We included 80 patients who underwent computed tomography (CT) and DT before pulmonary metastasectomy. One experienced chest radiologist annotated all visible nodules on thin-section CT scans using computer-aided detection software. Two radiologists used CT as the reference standard and retrospectively graded the visibility of nodules on DT. Nodule detection performance was evaluated in four sessions of 20 cases each by six readers. After each session, readers were unblinded to the DT images by revealing the true-positive markings and were instructed to self-analyze their own misreads. Receiver-operating-characteristic curves were determined. Among 414 nodules on CT, 53.3% (221/414) were visible on DT. The main reason for not seeing a nodule on DT was small size (93.3%, < or = 5 mm). DT revealed a substantial number of malignant nodules (84.1%, 143/170). The proportion of malignant nodules among visible nodules on DT was significantly higher (64.7%, 143/221) than that on CT (41.1%, 170/414) (p < 0.001). Area under the curve (AUC) values at the initial session were > 0.8, and the average detection rate for malignant nodules was 85% (210/246). The inter-session analysis of the AUC showed no significant differences among the readers, and the detection rate for malignant nodules did not differ across sessions. A slight improvement in reading times was observed. Most malignant nodules > 5 mm were visible on DT. As nodule detection performance was high from the initial session, DT may be readily applicable for radiology residents and board-certified radiologists.

Digital tomosynthesis for evaluating metastatic lung nodules: Nodule visibility, learning curves, and reading times

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Hee; Goo, Jin Mo; Lee, Sang Min; Park, Chang Min; Bahn, Young Eun; Kim, Hyung Jin; Song, Yong Sub; Hwang, Eui Jin [Dept. of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

2015-04-15

To evaluate nodule visibility, learning curves, and reading times for digital tomosynthesis (DT). We included 80 patients who underwent computed tomography (CT) and DT before pulmonary metastasectomy. One experienced chest radiologist annotated all visible nodules on thin-section CT scans using computer-aided detection software. Two radiologists used CT as the reference standard and retrospectively graded the visibility of nodules on DT. Nodule detection performance was evaluated in four sessions of 20 cases each by six readers. After each session, readers were unblinded to the DT images by revealing the true-positive markings and were instructed to self-analyze their own misreads. Receiver-operating-characteristic curves were determined. Among 414 nodules on CT, 53.3% (221/414) were visible on DT. The main reason for not seeing a nodule on DT was small size (93.3%, < or = 5 mm). DT revealed a substantial number of malignant nodules (84.1%, 143/170). The proportion of malignant nodules among visible nodules on DT was significantly higher (64.7%, 143/221) than that on CT (41.1%, 170/414) (p < 0.001). Area under the curve (AUC) values at the initial session were > 0.8, and the average detection rate for malignant nodules was 85% (210/246). The inter-session analysis of the AUC showed no significant differences among the readers, and the detection rate for malignant nodules did not differ across sessions. A slight improvement in reading times was observed. Most malignant nodules > 5 mm were visible on DT. As nodule detection performance was high from the initial session, DT may be readily applicable for radiology residents and board-certified radiologists.

Genesis and growth of internal microstructures of manganese nodule

Digital Repository Service at National Institute of Oceanography (India)

Banakar, V.K.; Tarkian, M.

tension of the 2 adjacent colloidal precipitate surfaces which have a tendency to grow into a spheroid, probably similar to phenomenon of drop formation. Detrital components within the nodule material identified include heavy titanium minerals, viz...

Role of baseline nodule density and changes in density and nodule features in the discrimination between benign and malignant solid indeterminate pulmonary nodules

NARCIS (Netherlands)

Xu, D.M.; van Klaveren, R.J.; de Bock, G.H.; Leusveld, A.L.M.; Dorrius, M.D.; Zhao, Y.; Wang, Y.; de Koning, H.J.; Scholten, E.T.; Verschakelen, J.; Prokop, M.; Oudkerk, M.

Purpose: To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules. Materials and methods: Solid indeterminate nodules between 50 and 500 mm(3) (4.6-9.8 mm) were assessed

Hypervascular hyperplastic nodules appearing in chronic alcoholic liver disease: benign intrahepatic nodules mimicking hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Won Kyu; Chang, Jay Chun; Kim, Jae Woon

2006-01-01

Hypervascular hyperplastic nodules in those patients with chronic alcoholic liver disease and who are hepatitis B and C negative have recently been reported on. The purpose of this study was to correlate the radiologic and pathologic findings with the clinical significance of these hypervascular hyperplastic nodules in chronic alcoholic liver disease. The study included eight hypervascular nodules of seven patients with chronic alcoholic liver disease, and these patients abused alcohol for more than 20 years. Eight hypervascular nodules were seen on the arterial phase of dynamic CT scans, but the possibility of HCC was excluded pathologically (n=4) or clinically. The radiologic and pathologic findings, and the changes of these nodules on follow up CT scans were retrospectively analyzed. All nodules showed good enhancement on the arterial phase. The tissue equilibrium phase of the dynamic CT scans showed isodensity in seven patients and low density in one patient. Ultrasound scans revealed hypoechoic findings for three nodules, isoechoic findings for two nodules, hyperechoic findings for one nodules, and two nodules were not detected. Angiograms (n=6) showed late incremental tumor staining, and all the nodules were well seen on the sinusoidal phase. CT during hepatic angiography (n=4) showed well stained tumor. CT during arterial portography (n=4) showed no defect in three nodules and nodular defect in on nodule. The MR images (n=3) showed low signal intensity in two nodules and iso-signal intensity in one nodule on T2WI. Five of six cases for which follow up CT scans were performed showed decrease in size and one was disappeared. Radiologically, it is often difficult to differentiate the hypervascular hyperplastic nodules seen in the chronic alcoholic liver disease from hepatocellular carcinoma, and histological confirmation is needed for excluded hepatocellular carcinoma. However, late tumor staining during the sinusoidal phase without any blood supply by feeding

Hypervascular hyperplastic nodules appearing in chronic alcoholic liver disease: benign intrahepatic nodules mimicking hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Park, Won Kyu; Chang, Jay Chun; Kim, Jae Woon [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)] (and others)

2006-02-15

Hypervascular hyperplastic nodules in those patients with chronic alcoholic liver disease and who are hepatitis B and C negative have recently been reported on. The purpose of this study was to correlate the radiologic and pathologic findings with the clinical significance of these hypervascular hyperplastic nodules in chronic alcoholic liver disease. The study included eight hypervascular nodules of seven patients with chronic alcoholic liver disease, and these patients abused alcohol for more than 20 years. Eight hypervascular nodules were seen on the arterial phase of dynamic CT scans, but the possibility of HCC was excluded pathologically (n=4) or clinically. The radiologic and pathologic findings, and the changes of these nodules on follow up CT scans were retrospectively analyzed. All nodules showed good enhancement on the arterial phase. The tissue equilibrium phase of the dynamic CT scans showed isodensity in seven patients and low density in one patient. Ultrasound scans revealed hypoechoic findings for three nodules, isoechoic findings for two nodules, hyperechoic findings for one nodules, and two nodules were not detected. Angiograms (n=6) showed late incremental tumor staining, and all the nodules were well seen on the sinusoidal phase. CT during hepatic angiography (n=4) showed well stained tumor. CT during arterial portography (n=4) showed no defect in three nodules and nodular defect in on nodule. The MR images (n=3) showed low signal intensity in two nodules and iso-signal intensity in one nodule on T2WI. Five of six cases for which follow up CT scans were performed showed decrease in size and one was disappeared. Radiologically, it is often difficult to differentiate the hypervascular hyperplastic nodules seen in the chronic alcoholic liver disease from hepatocellular carcinoma, and histological confirmation is needed for excluded hepatocellular carcinoma. However, late tumor staining during the sinusoidal phase without any blood supply by feeding

A higher yielding mutant of black gram with improved nodule formation

International Nuclear Information System (INIS)

Singh, R.K.; Raghuvanshi, S.S.

1987-01-01

Dry seeds of black gram (Vigna mungo (L) Hopper) var. T 9 with 12.2% moisture content were irradiated at 10, 20 and 30 krad of gamma rays. This was followed by combined treatment of one set in each dose with freshly prepared 0. 25% EMS in phosphate buffer at 7.0 pH at 30± deg. C for 6 hours. In M 2 population of 20 krad two mutants with pentafoliate instead of trifoliate leaves were found. This character was true breeding in M 3 M 6 generation. Crosses revealed monogenic recessive inheritance of this character. The proposed gene symbol is p5. This mutant has normal maturity period and the plant height is the same as T 9 (ca. 50 cm). Preliminary yield trials indicate superiority of the mutant line over control. The mutant line also shows a significant improvement in number and weight of root nodules, potentially improving green manuring value. Improvement of root nodulation in mungbean mutants was reported before by others

Emplacement of Xenolith Nodules in the Kaupulehu Lava Flow, Hualalai Volcano, Hawaii

Science.gov (United States)

Guest, J. E.; Spudis, P. D.; Greeley, R.; Taylor, G. J.; Baloga, S. M.

1995-01-01

The basaltic Kaupulehu 1800-1801 lava flow of Hualalai Volcano, Hawaii contains abundant ultramafic xenoliths. Many of these xenoliths occur as bedded layers of semi-rounded nodules, each thinly coated with a veneer (typically 1 mm thick) of lava. The nodule beds are analogous to cobble deposits of fluvial sedimentary systems. Although several mechanisms have been proposed for the formation of the nodule beds, it was found that, at more than one locality, the nodule beds are overbank levee deposits. The geological occurrence of the nodules, certain diagnostic aspects of the flow morphology and consideration of the inferred emplacement process indicate that the Kaupulehu flow had an exceptionally low viscosity on eruption and that the flow of the lava stream was extremely rapid, with flow velocities of at least 10 m/s (more than 40 km/h. This flow is the youngest on Hualalai Volcano and future eruptions of a similar type would pose considerable hazard to life as well as property.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

Science.gov (United States)

Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Search for Nodulation and Nodule Development-related cystatin genes in the genome of Soybean (Glycine max

Directory of Open Access Journals (Sweden)

Songli Yuan

2016-10-01

Full Text Available Nodulation, nodule development and senescence directly affects nitrogen fixation efficiency, and previous studies have shown that inhibition of some cysteine proteases delay nodule senescence, so their nature inhibitors, cystatin genes, are very important in nodulation, nodule development and senescence. Although several cystatins are actively transcribed in soybean nodules, their exact roles and functional diversities in legume have not been well explored in genome-wide survey studies. In this report, we performed a genome-wide survey of cystatin family genes to explore their relationship to nodulation and nodule development in soybean and identified 20 cystatin genes that encode peptides with 97~245 amino acid residues, different isoelectric points (pI and structure characteristics, and various putative plant regulatory elements in 3000 bp putative promoter fragments upstream of the 20 soybean cystatins in response to different abiotic/biotic stresses, hormone signals and symbiosis signals. The expression profiles of these cystatin genes in soybean symbiosis with rhizobium strain Bradyrhizobium japonicum strain 113-2 revealed that 7 cystatin family genes play different roles in nodulation as well as nodule development and senescence. However, these genes were not root nodule symbiosis (RNS - specific and did not encode special clade cystatin protein with structures related to nodulation and nodule development. Besides, only two of these soybean cystatins were not upregulated in symbiosis after ABA treatment. The functional analysis showed that a candidate gene Glyma.15G227500 (GmCYS16 was likely to play a positive role in soybean nodulation. Besides, evolutionary relationships analysis divided the cystatin genes from Arabidopsis thaliana, Nicotiana tabacum, rice, barley and four legume plants into three groups. Interestingly, Group A cystatins are special in legume plants, but only include one of the above-mentioned 7 cystatin genes related to

Auxin transport, metabolism, and signalling during nodule initiation: indeterminate and determinate nodules

NARCIS (Netherlands)

Kohlen, W.; Ng, Jason Liang Pin; Deinum, E.E.; Mathesius, Ulrike

2018-01-01

Most legumes can form a unique type of lateral organ on their roots: root nodules. These structures host symbiotic nitrogen-fixing bacteria called rhizobia. Several different types of nodules can be found in nature, but the two best-studied types are called indeterminate and determinate nodules.

Computed tomography of pulmonary nodules

International Nuclear Information System (INIS)

Nakata, Hajime; Honda, Hiroshi; Nakayama, Chikashi; Kimoto, Tatsuya; Nakayama, Takashi

1983-01-01

We have evaluated the value of computed tomography (CT) in distinguishing benign and malignant pulmonary nodules. CT was performed on 30 cases of solitary pulmonary nodules consisting of 17 primary lung cancers, 3 metastatic tumors and 10 benign nodules. The CT number was calculated for each lesion. Three benign nodules showed CT numbers well above the range of malignant nodules, and only in one of them was calcification visible on conventional tomography. In 6 benign nodules, the CT numbers overlapped those of malignant lesion and could not be differentiated. Thus the measurement of CT number can be useful to confirm the benign nature of certain nodules when calcification is unclear or not visible on conventional tomography. As for the morphological observation of the nodule, CT was not superior to conventional tomography and its value seems to be limited. (author)

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

Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... 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...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

Mineralogical and geochemical studies of phosphorite nodules in ...

African Journals Online (AJOL)

Mineralogical and geochemical studies of phosphorite nodules in the Dange Formation Sokoto Basin, Northwestern Niveria. OA Adekeye, SO Akande. Abstract. No Abstract Available Journal of Mining and Geology Vol.40(2) 2004: 101-106. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT ...

Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.

Science.gov (United States)

Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli

2018-03-01

Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

Micromonospora is a normal occupant of actinorhizal nodules

Indian Academy of Sciences (India)

Supplementary table 1. Number of isolates per nodule. Nodule Colonies Average Nodule Colonies Average. AV1 Nodule 1 2 13 EEM Nodule 1 17 9.4. Nodule 2 O Nodule 2 13. Nodule 3 2 Nodule 3 9. AV2 Nodule 1 19 16.1 Nodule 4 7. Nodule 2 25 Nodule 5 18. Nodule 3 38 Nodule 6 4. AV4 Nodule 1 8 14.0 Nodule 7 12.

Toxic effects of low concentrations of Cu on nodulation of cowpea (Vigna unguiculata)

International Nuclear Information System (INIS)

Kopittke, Peter M.; Dart, Peter J.; Menzies, Neal W.

2007-01-01

Although Cu is phytotoxic at Cu 2+ activities as low as 1-2 μM, the effect of Cu 2+ on the nodulation of legumes has received little attention. The effect of Cu 2+ on nodulation of cowpea (Vigna unguiculata (L.) Walp. cv. Caloona) was examined in a dilute solution culture system utilising a cation exchange resin to buffer solution Cu 2+ . The nodulation process was more sensitive to increasing Cu 2+ activities than both shoot and root growth; whilst a Cu 2+ activity of 1.0 μM corresponded to a 10% reduction in the relative yield of the shoots and roots, a Cu 2+ activity of 0.2 μM corresponded to a 10% reduction in nodulation. This reduction in nodulation with increasing Cu 2+ activity was associated with an inhibition of root hair formation in treatments containing ≥0.77 μM Cu 2+ , rather than to a reduction in the size of the Rhizobium population. - The nodulation process was more sensitive to increasing Cu 2+ activities than either shoot or root growth

Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice

Science.gov (United States)

McGee-Lawrence, Meghan E.; Carpio, Lomeli R.; Bradley, Elizabeth W.; Dudakovic, Amel; Lian, Jane B.; van Wijnen, Andre J.; Kakar, Sanjeev; Hsu, Wei; Westendorf, Jennifer J.

2014-01-01

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/− mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/− mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2−/−:Runx2+/− mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/− mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2−/−:Runx2+/− calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/− and double mutant Axin2−/−:Runx2+/− mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/− mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2−/− mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. PMID:24973690

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory NolR

Science.gov (United States)

The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory...

Effects of epidermal growth factor on bone formation and resorption in vivo

International Nuclear Information System (INIS)

Marie, P.J.; Hott, M.; Perheentupa, J.

1990-01-01

The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double [3H]proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse

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.

Identification of mechanosensitive genes during embryonic bone formation.

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Niamh C Nowlan

2008-12-01

Full Text Available Although it is known that mechanical forces are needed for normal bone development, the current understanding of how biophysical stimuli are interpreted by and integrated with genetic regulatory mechanisms is limited. Mechanical forces are thought to be mediated in cells by "mechanosensitive" genes, but it is a challenge to demonstrate that the genetic regulation of the biological system is dependant on particular mechanical forces in vivo. We propose a new means of selecting candidate mechanosensitive genes by comparing in vivo gene expression patterns with patterns of biophysical stimuli, computed using finite element analysis. In this study, finite element analyses of the avian embryonic limb were performed using anatomically realistic rudiment and muscle morphologies, and patterns of biophysical stimuli were compared with the expression patterns of four candidate mechanosensitive genes integral to bone development. The expression patterns of two genes, Collagen X (ColX and Indian hedgehog (Ihh, were shown to colocalise with biophysical stimuli induced by embryonic muscle contractions, identifying them as potentially being involved in the mechanoregulation of bone formation. An altered mechanical environment was induced in the embryonic chick, where a neuromuscular blocking agent was administered in ovo to modify skeletal muscle contractions. Finite element analyses predicted dramatic changes in levels and patterns of biophysical stimuli, and a number of immobilised specimens exhibited differences in ColX and Ihh expression. The results obtained indicate that computationally derived patterns of biophysical stimuli can be used to inform a directed search for genes that may play a mechanoregulatory role in particular in vivo events or processes. Furthermore, the experimental data demonstrate that ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators in translating information from the mechanical environment to the

PDLLA honeycomb-like scaffolds with a high loading of superhydrophilic graphene/multi-walled carbon nanotubes promote osteoblast in vitro functions and guided in vivo bone regeneration.

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Silva, Edmundo; Vasconcellos, Luana Marotta Reis de; Rodrigues, Bruno V M; Dos Santos, Danilo Martins; Campana-Filho, Sergio P; Marciano, Fernanda Roberta; Webster, Thomas J; Lobo, Anderson Oliveira

2017-04-01

Herein, we developed honeycomb-like scaffolds by combining poly (d, l-lactic acid) (PDLLA) with a high amount of graphene/multi-walled carbon nanotube oxides (MWCNTO-GO, 50% w/w). From pristine multi-walled carbon nanotubes (MWCNT) powders, we produced MWCNTO-GO via oxygen plasma etching (OPE), which promoted their exfoliation and oxidation. Initially, we evaluated PDLLA and PDLLA/MWCNTO-GO scaffolds for tensile strength tests, cell adhesion and cell viability (with osteoblast-like MG-63 cells), alkaline phosphatase (ALP, a marker of osteoblast differentiation) activity and mineralized nodule formation. In vivo tests were carried out using PDLLA and PDLLA/MWCNTO-GO scaffolds as fillers for critical defects in the tibia of rats. MWCNTO-GO loading was responsible for decreasing the tensile strength and elongation-at-break of PDLLA scaffolds, although the high mechanical performance observed (~600MPa) assures their application in bone tissue regeneration. In vitro results showed that the scaffolds were not cytotoxic and allowed for osteoblast-like cell interactions and the formation of mineralized matrix nodules. Furthermore, MG-63 cells grown on PDLLA/MWCNTO-GO significantly enhanced osteoblast ALP activity compared to controls (cells alone), while the PDLLA group showed similar ALP activity when compared to controls and PDLLA/MWCNTO-GO. Most impressively, in vivo tests suggested that compared to PDLLA scaffolds, PDLLA/MWCNTO-GO had a superior influence on bone cell activity, promoting greater new bone formation. In summary, the results of this study highlighted that this novel scaffold (MWCNTO-GO, 50% w/w) is a promising alternative for bone tissue regeneration and, thus, should be further studied. Copyright © 2016 Elsevier B.V. All rights reserved.

A higher yielding mutant of black gram with improved nodule formation

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Singh, R K; Raghuvanshi, S S [Plant Genetic Unit, Department of Botany, University of Lucknow (India)

1987-07-01

Dry seeds of black gram (Vigna mungo (L) Hopper) var. T{sub 9} with 12.2% moisture content were irradiated at 10, 20 and 30 krad of gamma rays. This was followed by combined treatment of one set in each dose with freshly prepared 0. 25% EMS in phosphate buffer at 7.0 pH at 30{+-} deg. C for 6 hours. In M{sub 2} population of 20 krad two mutants with pentafoliate instead of trifoliate leaves were found. This character was true breeding in M{sub 3} M{sub 6} generation. Crosses revealed monogenic recessive inheritance of this character. The proposed gene symbol is p5. This mutant has normal maturity period and the plant height is the same as T{sub 9} (ca. 50 cm). Preliminary yield trials indicate superiority of the mutant line over control. The mutant line also shows a significant improvement in number and weight of root nodules, potentially improving green manuring value. Improvement of root nodulation in mungbean mutants was reported before by others.

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

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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.

Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis

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Santos, Vitorino Modesto dos; Lima, Marcus Aurelho de; Marinho, Euripedes Oliveira; Marinho, Marco Aurelio de Oliveira; Santos, Lister Arruda Modesto dos; Raphael, Cristiane Mendes [Universidade do Triangulo Mineiro, Uberlandia, MG (Brazil). Faculdade de Medicina. Dept. de Clinica Medica

2000-04-01

A case of parasitic thyroid nodule is presented. The patient was a non symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid trauma or surgery, she presented a 1.6 x 0.7 x 0.5 cm right pre-laryngeal lymph node-like mass which, on ultrasonography, appeared distinct from the gland. TSH, thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated and T4-free level was normal. Thyroid and total body {sup 99m} Tc isonitrile scintiscan showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle aspiration of the nodule showed epithelial cells with nuclear atypia and oncocitic changes plus intense lymphoid infiltration and germinative center formation, simulating lymph node metastasis of papillary thyroid carcinoma. Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic thyroiditis. Parasitic thyroid nodule must always be remembered so that unnecessary surgical assessment and undesirable sequels may be avoided. (author)

Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation.

Science.gov (United States)

Ghanaati, Shahram; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin; Stuebinger, Stefan; Korzinskas, Tadas; Obreja, Karina; Landes, Constantin; Kirkpatrick, Charles J; Sader, Robert A

2013-12-01

In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into the most cranial parts of the augmented region. There was no statistically significant difference in new bone formation after 3 and 6 months (24.89 ± 10.22% vs 31.29 ± 2.29%), respectively. Within the limits of the present study and according to previously published data, implant insertion in regions augmented with this bone substitute material could be considered already after 3 months. Further clinical studies with bone substitute materials are necessary to validate these findings. © 2012 Wiley Periodicals, Inc.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Science.gov (United States)

Blake, Glen M; Puri, Tanuj; Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac

2018-02-01

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([ 18 F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [ 18 F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [ 18 F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [ 18 F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family.

Science.gov (United States)

Ripamonti, Ugo; Parak, Ruqayya; Klar, Roland M; Dickens, Caroline; Dix-Peek, Thérèse; Duarte, Raquel

2016-10-01

The momentum to compose this Leading Opinion on the synergistic induction of bone formation suddenly arose when a simple question was formulated during a discussion session on how to boost the often limited induction of bone formation seen in clinical contexts. Re-examination of morphological and molecular data available on the rapid induction of bone formation by the recombinant human transforming growth factor-β3 (hTGF-β3) shows that hTGF-β3 replicates the synergistic induction of bone formation as invocated by binary applications of hOP-1:hTGF-β1 at 20:1 by weight when implanted in heterotopic sites of the rectus abdominis muscle of the Chacma baboon, Papio ursinus. The rapid induction of bone formation in primates by hTGF-β3 may stem from bursts of cladistic evolution, now redundant in lower animal species but still activated in primates by relatively high doses of hTGF-β3. Contrary to rodents, lagomorphs and canines, the three mammalian TGF-β isoforms induce rapid and substantial bone formation when implanted in heterotopic rectus abdominis muscle sites of P. ursinus, with unprecedented regeneration of full thickness mandibular defects with rapid mineralization and corticalization. Provocatively, thus providing potential molecular and biological rationales for the apparent redundancy of osteogenic molecular signals in primates, binary applications of recombinant human osteogenic protein-1 (hOP-1) with low doses of hTGF-β1 and -β3, synergize to induce massive ossicles in heterotopic rectus abdominis, orthotopic calvarial and mandibular sites of P. ursinus. The synergistic binary application of homologous but molecularly different soluble molecular signals has indicated that per force several secreted molecular signals are required singly, synchronously and synergistically to induce optimal osteogenesis. The morphological hallmark of the synergistic induction of bone formation is the rapid differentiation of large osteoid seams enveloping

Role of Duplex Power Doppler Ultrasound in Differentiation between Malignant and Benign Thyroid Nodules

International Nuclear Information System (INIS)

Algin, Oktay; Algin, Efnan; Gokalp, Gokhan; Ocakog, Gokhan; Erdog an, Cuneyt; Saraydaroglu, Ozlem; Ercan Tuncel, Prof

2010-01-01

To evaluate the usage of duplex power Doppler ultrasound (PDUS) for the differentiation of benign and malignant thyroid nodules. We prospectively examined 77 thyroid nodules in 60 patients undergoing ultrasound-guided fine needle aspiration biopsy (FNAB). Each nodule was described according to size, inner structure, borders, parenchymal echogenicity, peripheral halo formation, and the presence of calcification (Bmode ultrasound findings). Vascularity as determined by PDUS imaging was defined as non-vascular, peripheral, central, or of mixed type. For each nodule, the pulsatility index (PI) and resistive index (RI) values were obtained. Results of FNAB and surgical pathological examination (if available) were used as a proof of final diagnosis to categorize all nodules as benign or malignant. A receiver operating characteristic (ROC) curve analysis was performed to establish cut-off, sensitivity, and specificity values associated with RI-PI values. A significant relationship was observed between malignancy and irregular margins, microcalcifications, and hypoechogenicity on ultrasound examination (p 0.05). The central, peripheral, and mean RI-PI values were higher in malignant nodules when compared to the other cytologies (p < 0.05). Vascularity is not a useful parameter for distinguishing malignant from benign thyroid nodules. However, RI and PI values are useful in distinguishing malignant from benign thyroid nodules

Canola and hydrogenated soybean oils accelerate ectopic bone formation induced by implantation of bone morphogenetic protein in mice

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Yoko Hashimoto

2014-01-01

Full Text Available Canola oil (Can and hydrogenated soybean oil (H2-Soy are commonly used edible oils. However, in contrast to soybean oil (Soy, they shorten the survival of stroke-prone spontaneously hypertensive (SHRSP rats. It has been proposed that the adverse effects of these oils on the kidney and testis are caused at least in part by dihydro-vitamin K (VK 1 in H2-Soy and unidentified component(s in Can. Increased intake of dihydro-VK1 is associated with decreased tissue VK2 levels and bone mineral density in rats and humans, respectively. The aim of the present study was to determine the effects of these oils on bone morphogenetic protein (BMP-induced ectopic bone formation, which is promoted by VK2 deficiency, in relation to the role of VK in the γ-carboxylation of osteocalcin and matrix Gla protein. A crude extract of BMPs was implanted into a gap in the fascia of the femoral muscle in 5-week-old mice maintained on a Soy, Can, or H2-Soy diet. Newly formed bone volume, assessed by three-dimensional X-ray micro-computed tomography and three-dimensional reconstruction imaging for bone, was 4-fold greater in the Can and H2-Soy groups than in the Soy group. The plasma carboxylated osteocalcin (Gla-OC and total OC (Gla-OC plus undercarboxylated osteocalcin [Glu-OC] levels were significantly lower in the Can group than in the Soy group (p < 0.05. However, these levels did not significantly differ between the H2-Soy and Soy groups. The plasma Gla-OC/Glu-OC ratio in the Can and H2-Soy groups was significantly lower (in Can; p = 0.044 or was almost significantly lower (in H2-Soy; p = 0.053 than that in the Soy group. In conclusion, Can and H2-Soy accelerated BMP-induced bone formation in mice to a greater extent than Soy. Further research is required to evaluate whether the difference in accelerated ectopic bone formation is associated with altered levels of VK2 and VK-dependent protein(s among the three dietary groups.

Influence of controlled immediate loading and implant design on peri-implant bone formation.

Science.gov (United States)

Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

2007-02-01

Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (pimplant contact occurred was the highest for SL and significantly different from SU (pimplant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

Directory of Open Access Journals (Sweden)

Kyu Sang Joeng

Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

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

International Nuclear Information System (INIS)

Yucel, Aylin; Acar, Murat; Kuru, Ilhami; Bozan, M. Eray; Solak, Mustafa

2005-01-01

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.)

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

DEFF Research Database (Denmark)

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

2014-01-01

on the bone surface from the marrow cavity. The present study on human iliac crest biopsy specimens reveals that BRC canopies appear frequently absent above both eroded and formative surfaces in post-menopausal osteoporosis patients, and that this absence was associated with bone loss in these patients...... surfaces was associated with a shift in the osteoblast morphological characteristics, from cuboidal to flattened. Collectively, this study shows that the BRCs are unique anatomical structures implicated in bone remodeling in a widespread disease, such as post-menopausal osteoporosis. Furthermore...

Solitary pulmonary nodule

Science.gov (United States)

... Adenocarcinoma - chest x-ray Pulmonary nodule - front view chest x-ray Pulmonary nodule, solitary - CT scan Respiratory system References Gotway MB, Panse PM, Gruden JF, Elicker BM. Thoracic radiology: noninvasive diagnostic imaging. In: Broaddus VC, Mason RJ, ...

Recent advances in non-vascular interventional diagnosis and treatment of thyroid nodules

International Nuclear Information System (INIS)

Lu Liming; Zhou Weisheng

2009-01-01

Non-vascular interventional diagnostic methods of thyroid nodules include ultrasonography-guided fine-needle aspiration cytology (USgFNAC) and ultrasonography-guided core-needle biopsy (USgCNB). USgFNAC is a practical method used to select and to guide the treatment of various thyroid nodules, however, it is difficult to make a differentiation between benign and malignant lesions simply to rely on the findings of a small number of cells. USgCNB has the advantage of being able to obtain satisfactory specimen enough for making a histological diagnosis, although this procedure is contraindicated in some patients. Non-vascular interventional treatments of thyroid nodules include percutaneous ethanol injection (PEI) and ultrasonography-guided interstitial laser photocoagulation (USgILP). Both PEI and USgILP have fine effect on the benign thyroid nodules. Compared with PEI, laser-induced necrosis can be well controlled, thus, the adverse reactions, such as the formation of fibrosis adjacent to the nodule, vocal cord paralysis, etc. can be avoided.Non-vascular interventional treatments may cause some untoward effects. For the diagnosis and treatment of thyroid nodules, the non-vascular interventional procedure is simple, safe, effective and economic with less complications, therefore, this technique is worth being popularized in clinical practice. (authors)

Toxic effects of low concentrations of Cu on nodulation of cowpea (Vigna unguiculata)

Energy Technology Data Exchange (ETDEWEB)

Kopittke, Peter M. [School of Land and Food Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)]. E-mail: p.kopittke@uq.edu.au; Dart, Peter J. [School of Land and Food Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Menzies, Neal W. [School of Land and Food Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)

2007-01-15

Although Cu is phytotoxic at Cu{sup 2+} activities as low as 1-2 {mu}M, the effect of Cu{sup 2+} on the nodulation of legumes has received little attention. The effect of Cu{sup 2+} on nodulation of cowpea (Vigna unguiculata (L.) Walp. cv. Caloona) was examined in a dilute solution culture system utilising a cation exchange resin to buffer solution Cu{sup 2+}. The nodulation process was more sensitive to increasing Cu{sup 2+} activities than both shoot and root growth; whilst a Cu{sup 2+} activity of 1.0 {mu}M corresponded to a 10% reduction in the relative yield of the shoots and roots, a Cu{sup 2+} activity of 0.2 {mu}M corresponded to a 10% reduction in nodulation. This reduction in nodulation with increasing Cu{sup 2+} activity was associated with an inhibition of root hair formation in treatments containing {>=}0.77 {mu}M Cu{sup 2+}, rather than to a reduction in the size of the Rhizobium population. - The nodulation process was more sensitive to increasing Cu{sup 2+} activities than either shoot or root growth.

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.

Science.gov (United States)

Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

2014-07-01

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

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.

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

Directory of Open Access Journals (Sweden)

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

The effect of patient age on bone formation using a fully synthetic nanocrystalline bone augmentation material in maxillary sinus grafting.

Science.gov (United States)

Wolf, Michael; Wurm, Alexander; Heinemann, Friedhelm; Gerber, Thomas; Reichert, Christoph; Jäger, Andreas; Götz, Werner

2014-01-01

Maxillary sinus floor augmentation is a treatment that has been proposed for patients in whom the alveolar bone height is insufficient. This procedure is commonly used in patients aged 40 to 70 years and older. However, little information exists whether the factor of age might influence the outcome of augmentation procedures. The aim of this study was to investigate whether the patient's age has an effect on bone formation and incorporation in maxillary sinus floor augmentation procedures. A fully synthetic nanocrystalline bone augmentation material (NanoBone, Artoss) was used for sinus floor augmentation in patients with a subantral vertical bone height of at least 3 mm and maximum of 7 mm. After 7 months healing time, biopsy specimens were taken and were divided into two groups according to the patient's age. Exclusion criteria were poor general health (eg, severe renal/and or liver disease), history of a radiotherapy in the head region, chemotherapy at the time of surgical procedure, noncompensated diabetes mellitus, symptoms of a maxillary sinus disease, active periodontal or systemic diseases, smoking, and poor oral hygiene. Histologic analyses with hematoxylin-eosin stain were performed. Multinucleated osteoclast-like cells were identified by histochemical staining (tartrate-resistant acid phosphatase [TRAP]). Quantitative and age-dependent assessment of bone formation, residual bone grafting material, and soft tissue formation following sinus augmentation was performed using histomorphometric analysis and the Bonferroni adjustment of the Student t test. Twenty biopsy specimens from 17 patients were taken and divided into two groups according to age (group 1: 41 to 52 years; group 2: 66 to 71 years) containing 10 specimens each, which were analyzed in triplicate resulting in a total of 30 specimens per group. A regeneration process with varying amounts of newly formed bone surrounded by marrow-like tissue was present in all augmented regions. No signs of

[The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

Science.gov (United States)

Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

2003-09-01

To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

Science.gov (United States)

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characteristic CT Findings After Percutaneous Cryoablation Treatment of Malignant Lung Nodules.

Science.gov (United States)

Chaudhry, Ammar; Grechushkin, Vadim; Hoshmand, Mahsa; Kim, Choo Won; Pena, Andres; Huston, Brett; Chaya, Yair; Bilfinger, Thomas; Moore, William

2015-10-01

subsequent gradual decrease in the surface area. Decreased nodule density (Hounsfield units) at each interval follow-up is associated with complete ablation of the lung cancer whereas increasing nodule density was suggestive of recurrence. Cavity formation within the region of the ablated nodule, most of which typically resolved within the first 3 to 6 months. Nodule enhancement is difficult to assess because of the limited data sets that are available.

Can Lung Nodules Be Cancerous?

Science.gov (United States)

... lung nodules be cancerous? Answers from Eric J. Olson, M.D. Yes, lung nodules can be cancerous, ... to determine if it's cancerous. With Eric J. Olson, M.D. AskMayoExpert. Pulmonary nodules. Rochester, Minn.: Mayo ...

57Fe Moessbauer spectroscopic characterisation of a ferromanganese nodule from the Central Indian Ocean

International Nuclear Information System (INIS)

Dutta, R.K.; Chakravortty, V.

1997-01-01

The iron bearing phases present in a ferromanganese nodule from the Central Indian Ocean have been determined using 57 Fe Moessbauer spectroscopy. The Moessbauer results have been corroborated by XRD, IR and TG-DTA studies. The Moessbauer spectrum of a ferromanganese nodule shows a broad line width which indicates the presence of more than one iron bearing paramagnetic oxide or oxyhydroxide phases where iron is present as Fe 3+ . γ-FeOOH has been distinctly characterised as one of the iron bearing phases in the nodule. Other oxyhydroxide and oxide phases of iron in the nodule have been ruled out. A typical paramagnetic doublet persists even at very high temperature which has been proposed to be due to iron(III)phosphate. Formation of solid solution of Mn 2 O 3 -Fe 2 O 3 has been observed in the heat treated nodule at 1073 K, which has been characterised by the Moessbauer technique. (author)

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR.

Science.gov (United States)

Lee, Soon Goo; Krishnan, Hari B; Jez, Joseph M

2014-04-29

The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory protein. Here, we present the X-ray crystal structures of NolR in the unliganded form and complexed with two different 22-base pair (bp) double-stranded operator sequences (oligos AT and AA). Structural and biochemical analysis of NolR reveals protein-DNA interactions with an asymmetric operator site and defines a mechanism for conformational switching of a key residue (Gln56) to accommodate variation in target DNA sequences from diverse rhizobial genes for nodulation and symbiosis. This conformational switching alters the energetic contributions to DNA binding without changes in affinity for the target sequence. Two possible models for the role of NolR in the regulation of different nodulation and symbiosis genes are proposed. To our knowledge, these studies provide the first structural insight on the regulation of genes involved in the agriculturally and ecologically important symbiosis of microbes and plants that leads to nodule formation and nitrogen fixation.

Benthic communities associated with ferromanganese nodules from the Central Indian Ocean

Digital Repository Service at National Institute of Oceanography (India)

Ingole, B.S.; Pavithran, S.; Goltekar, R.

for grazers, shelter for burrowers and sessile organisms as well as protection for mobile fauna. It is concluded that benthic organisms like nematodes, polychaetes and foraminiferas may have strong influence on nodule formation and growth....

High-temperature thermomagnetic properties of vivianite nodules, Lake El'gygytgyn, Northeast Russia

Directory of Open Access Journals (Sweden)

P. S. Minyuk

2013-02-01

Full Text Available Vivianite, a hydrated iron phosphate, is abundant in sediments of Lake El'gygytgyn, located in the Anadyr Mountains of central Chukotka, northeastern Russia (67°30′ N, 172°05′ E. Magnetic measurements, including mass-specific low-field AC magnetic susceptibility, field-dependent magnetic susceptibility, hysteresis parameters, temperature dependence of the induced magnetization, as well as susceptibility in different heating media, provide ample information on vivianite nodules. Electron microprobe analyses, electron microscopy and energy dispersive spectroscopy were used to identify diagnostic minerals. Vivianite nodules are abundant in both sediments of cold (anoxic and warm (oxic stages. Magnetic susceptibility of the nodules varies from 0.78 × 10−6 m3 kg−1 to 1.72 × 10−6 m3 kg−1 (average = 1.05 × 10−6 m3 kg−1 and is higher than the susceptibility of sediments from the cold intervals. Magnetic properties of vivianite are due to the respective product of oxidation as well as sediment and mineral inclusions. Three types of curves for high-temperature dependent susceptibility of vivianite indicate different degrees of oxidation and inclusions in the nodules. Vivianite acts as a reductant and reduces hematite to magnetite and masks the goethite–hematite transition during heating. Heating vivianite and sulfur mixtures stimulates the formation of monoclinic pyrrhotite. An additive of arsenic inhibits the formation of magnetite prior to its Curie temperature. Heating selective vivianite and pyrite mixtures leads to formation of several different minerals – magnetite, monoclinic pyrrhotite, and hexagonal pyrrhotite, and makes it difficult to interpret the thermomagnetic curves.

"Ruffled border" formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over.

Science.gov (United States)

Merolli, Antonio; Fung, Stephanie; Murthy, N Sanjeeva; Pashuck, E Thomas; Mao, Yong; Wu, Xiaohuan; Steele, Joseph A M; Martin, Daniel; Moghe, Prabhas V; Bromage, Timothy; Kohn, Joachim

2018-03-21

Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the "actin ring" and the "ruffled border", which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior.

Heterotopic bone formation (myositis ossificans) and lower-extremity swelling mimicking deep-venous disease

International Nuclear Information System (INIS)

Orzel, J.A.; Rudd, T.G.; Nelp, W.B.

1984-01-01

A quadriplegic patient with a swollen leg was suspected of having deep-venous thrombosis, and was studied with radionuclide venography (RNV) and contrast venography. Focal narrowing of the femoral vein, seen on RNV, was due to extrinsic compression. Although soft-tissue radiographs were normal, Tc-99m diphosphonate imaging established the diagnosis of early heterotopic bone formation (myositis ossificans), which was responsible for the venous compression. Clinically this inflammatory process can mimic deep-venous thrombosis, and should be considered in evaluating patients at risk for both heterotopic bone formation and deep-venous thrombosis

Management of Pulmonary Nodules

OpenAIRE

Arvin Aryan

2010-01-01

Pulmonary nodule characterization is currently being redefined as new clinical, radiological and pathological data are reported, necessitating a reevaluation of the clinical management."nIn approach to an incidentally detected pulmonary nodule, we should consider that there are different risk situations, different lesion morphologies, and different sizes with various management options."nIn this session we will review the different risk situations for patients with pulmonary nodules...

Two negative regulatory systems of root nodule symbiosis - how are symbiotic benefits and costs balanced?

Science.gov (United States)

Nishida, Hanna; Suzaki, Takuya

2018-05-30

Root nodule symbiosis is one of the best-characterized mutualistic relationships between plants-microbes symbiosis, where mainly leguminous species can obtain nitrogen sources fixed by nitrogen-fixing rhizobia through the formation of symbiotic organs root nodules. In order to drive this symbiotic process, plants need to provide carbon sources that should be used for their growth. Therefore, a balance between the benefits of obtaining nitrogen sources and the costs of losing carbon sources needs to be maintained during root nodule symbiosis. Plants have developed at least two negative regulatory systems of root nodule symbiosis. One strategy involves the regulation of nodule number in response to rhizobial infection. For this regulation, a systemic long-range signaling between roots and shoots called autoregulation of nodulation has a pivotal role. Another strategy involves the regulation of root nodule symbiosis in response to nitrate, the most abundant form of nitrogen nutrients in the soil. Recent studies indicate that a long-distance signaling is shared between the two strategies, where NIN and NRSYM1, two paralogous RWP-RK transcription factors, can activate the production of nodulation-related CLE peptides in response to different inputs. Here, we give an overview of such progress in our understanding of molecular mechanisms relevant to the control of the symbiotic balance, including their biological significance.

99mTechnetium-methylene diphosphonate bone imaging using low-intensity pulsed ultrasound: promotion of bone formation during mandibular distraction osteogenesis in dogs.

Science.gov (United States)

Ding, Yuxiang; Li, Guoquan; Ao, Jianhua; Zhou, Libin; Ma, Qin; Liu, Yanpu

2010-03-01

Our objective was to assess the value of (99m)technetium-methylene diphosphonate ((99m)Tc-MDP) bone imaging in the use of low-intensity pulsed ultrasound to promote bony formation during mandibular distraction osteogenesis in dogs. The body of the mandibles in 7 dogs were cut between the first and the second premolar and were lengthened at the rate of 1mm/day, twice a day, for 20 days. During the period of distraction one lateral distraction gap was irradiated with low-intensity pulsed ultrasound (LIPUS) for 10min twice a day, and the other side was used as control. Serial radiographic inspections were made at different periods (0, 1, 2, 4, 6, 8, and 12 weeks) during the consolidation phase, followed by a plain radiograph and histological examination. The (99m)Tc-MDP imaging showed that the ratio of bone formation on the LIPUS-treated side was significantly higher than that on the control side during the early period of consolidation (before the 4th week), but later this was reversed and there were no significant differences between the two sides by the 12th week. Plain radiographs and histological examination showed that the new bone on the experimental side had matured earlier than that on the control side. Radionuclide bone imaging is a good way to assess the formation of bone after distraction osteogenesis.

Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption

DEFF Research Database (Denmark)

Karsdal, M.A.; Henriksen, K.; Sorensen, M.G.

2005-01-01

Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhi...

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

is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes...... an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15...

Buried and Surface Polymetallic Nodule Distribution in the Eastern CLARION-CLIPPERTON Zone: Main Distinctions and Similarities

Science.gov (United States)

Kotlinski, R.; Stoyanova, V.

The distribution pattern, abundance variations, morphology, chemical and mineralogical composition of buried polymetallic nodules in the eastern Clarion-Clipperton Zone (CCZ) are presented. Our observations are based on data collected from 59 boxcore stations, which comprise about 22.6% of all sampled stations in the Interoceanmetal exploration area site B2 in the eastern CCZ, with recorded buried and surface polymetallic nodules. The majority of stations with buried nodules (>90%) is below 4300 m water depth and is associated mainly with seafloor hills and slopes of ridges and depressions. Buried nodules lie completely beneath the active sediment-water boundary layer (with thickness range from 0 to 15 cm), and they are vertically recorded down to the 45 cm in sediment cores. Abundance of buried nodules varies from 0.2 to 22.1 kg/m2, averaging 3.2 kg/m2. By comparison, surface nodules are more abundant, varying from 0 to 20.2 kg/m2, averaging 10.3 kg/m2. As a general rule the size of buried nodules is larger than surface nodules, and >27% of recovered buried nodules exceed 10 cm in diameter. It is assumed that more than 90% of analyzed buried nodules have a diagenetic origin; however, the identification of factors and conditions responsible for their formation still remains unknown.

Short-term molecular acclimation processes of legume nodules to increased external oxygen concentration

Directory of Open Access Journals (Sweden)

Ulrike eAvenhaus

2016-01-01

Full Text Available Nitrogenase is an oxygen labile enzyme. Microaerobic conditions within the infected zone of nodules are maintained primarily by an oxygen diffusion barrier located in the nodule cortex. Flexibility of the oxygen diffusion barrier is important for the acclimation processes of nodules in response to changes in external oxygen concentration. The hypothesis of the present study was that there are additional molecular mechanisms involved. Nodule activity of Medicago truncatula plants were continuously monitored during a change from 21 to 25 or 30 % oxygen around root nodules by measuring nodule H2 evolution. Within about two minutes of the increase in oxygen concentration, a steep decline in nitrogenase activity occurred. A quick recovery commenced about eight minutes later. A qPCR-based analysis of the expression of genes for nitrogenase components showed a tendency towards upregulation during the recovery. The recovery resulted in a new constant activity after about 30 minutes, corresponding to approximately 90 % of the pre-treatment level. An RNAseq-based comparative transcriptome profiling of nodules at that point in time revealed that genes for nodule-specific cysteine-rich (NCR peptides, defensins, leghaemoglobin and chalcone and stilbene synthase were significantly upregulated when considered as a gene family. A gene for a nicotianamine synthase-like protein (Medtr1g084050 showed a strong increase in count number. The gene appears to be of importance for nodule functioning, as evidenced by its consistently high expression in nodules and a strong reaction to various environmental cues that influence nodule activity. A Tnt1-mutant that carries an insert in the coding sequence (cds of that gene showed reduced nitrogen fixation and less efficient acclimation to an increased external oxygen concentration. It was concluded that sudden increases in oxygen concentration around nodules destroy nitrogenase, which is quickly counteracted by an increased

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

2011-06-01

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. © 2011

Medicago truncatula ENOD40-1 and ENOD40-2 are both involved in nodule initiation and bacteroid development

NARCIS (Netherlands)

Wan, X.; Hontelez, J.; Lillo, A.; Guarnerio, C.; Peut, van de D.; Fedorova, E.; Bisseling, T.; Franssen, H.

2007-01-01

The establishment of a nitrogen-fixing root nodule on legumes requires the induction of mitotic activity of cortical cells leading to the formation of the nodule primordium and the infection process by which the bacteria enter this primordium. Several genes are up-regulated during these processes,

CSA-90 Promotes Bone Formation and Mitigates Methicillin-resistant Staphylococcus aureus Infection in a Rat Open Fracture Model.

Science.gov (United States)

Mills, Rebecca; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Isaacs, David; Genberg, Carl; Savage, Paul B; Little, David G; Schindeler, Aaron

2018-06-01

treatment with 500 µg CSA-90 were performed at Day 1 and Day 5 after injury and bacterial insult (S aureus). All animals were reviewed daily for signs of local infection and/or sepsis. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats showing osteolysis and/or declining overall health were culled at his instruction. The primary outcome of both fracture studies was fracture infection, incorporating survival, radiographic union, and deep tissue swab cultures. For the ectopic bone formation assay, 0 to 10 µg BMP-2 and 0 to 500 µg CSA-90 were delivered on a collagen sponge into bilateral quadriceps muscle pouches of 8-week-old rats (n = 10 per group). Micro-CT quantification of bone volume and descriptive histologic analysis were performed for all in vivo studies. Modified Kirby-Bauer disc diffusion assays were used to quantify antimicrobial activity in vitro using four different delivery methods, including bone cement. Infection was observed in none of the MRSA inoculated open fractures treated with CSA-90 with 10 of 10 deep tissue swab cultures negative at the time of cull. Median survival was 43 days (range, 11-43 days) in the treated group versus 11 days (range, 8-11 days) in the untreated MRSA inoculated group (p open fractures with CSA-90 at either Day 1 or Day 5 did not prevent infection, resulting in early culls by Day 21 with positive swab cultures (10 of 10 for each time point). Maximal ectopic bone formation was achieved with 500 μg CSA-90 and 10 μg BMP-2 (mean volume, 9.58 mm; SD, 7.83), creating larger bone nodules than formed with 250 μg CSA-90 and 10 μg BMP-2 (mean volume, 1.7 mm; SD, 1.07; p open fracture infection. The antimicrobial properties of CSA-90 combined with further evidence of its proosteogenic potential make it a promising compound to develop further for orthopaedic applications.

Comparison of muscle-to-nodule and parenchyma-to-nodule strain ratios in the differentiation of benign and malignant thyroid nodules: Which one should we use?

Energy Technology Data Exchange (ETDEWEB)

Aydin, Ramazan, E-mail: raydin1984@hotmail.com [Department of Radiology, Samsun Education and Research Hospital, Samsun (Turkey); Elmali, Muzaffer, E-mail: muzafel@yahoo.com.tr [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Polat, Ahmet Veysel, E-mail: veyselp@hotmail.com [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Danaci, Murat, E-mail: danacim55@yahoo.com [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Akpolat, Ilkser, E-mail: ilkserakpolat@yahoo.com [Department of Pathology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey)

2014-03-15

Objective: The aim of this study is to investigate the diagnostic accuracy of muscle-to-nodule strain ratio (MNSR) in the differentiation of benign and malignant thyroid nodules and to see if there was a difference between MNSR and parenchyma-to-nodule strain ratios (PNSR) in diagnosis. Methods: A total of 106 consecutive patients (88 women and 18 men; age range 19–79 years) with thyroid nodules were prospectively examined using ultrasound and sonoelastography before the fine-needle aspiration biopsy. The mean MNSR and PNSR were calculated for each nodule and the elasticity score was determined according to four-point scoring system. Results: According to the four-point scoring system, 44 of the 83 benign nodules had a score of one or two while 22 of the 23 malignant nodules had a score of three or four (p < 0.001). Using ROC analysis, the best cutoff point for MNSR 1.85 and for PNSR 3.14 was calculated. The sensitivity and specificity for the MNSR were 95.6%, 92.8%, respectively; for the PNSR were 95.6%, 93.4%, respectively, when the best cutoff points were used (p < 0.001). The κ value for the PNSR and MNSR methods was 0.87, which indicated an almost perfect agreement (p < 0.001). Conclusions: Sonoelastography has a high diagnostic accuracy in the differentiation of benign and malignant thyroid nodules. There was no significant difference between MNSR and PNSR in the differentiation of benign and malignant thyroid nodules. Therefore, we think that MNSR could safely be used in situations where PNSR could not be used.

Recent metalliferous sediment in the North Pacific manganese nodule area

Science.gov (United States)

Bischoff, J.L.; Rosenbauer, R.J.

1977-01-01

Quaternary sediments cored in the northeast Pacific nodule area (DOMES site C, 14??N, 126??W) contain a significant amount of hydrothermal metalliferous mud. Water content, color, mineralogy, and chemical composition are analogous to metalliferous sediments of the subequatorial East Pacific Rise. Correction for contribution of pelagic clay indicates the metalliferous fraction to be about 40% of the sediment. SiO2 and Mg are major components in the corrected composition, as they are for other metalliferous sediments similarly corrected from a variety of East Pacific Rise and DSDP metalliferous sediments. A correlation between Mg and SiO2 for these corrected sediments could indicate a hydrothermal origin for a significant portion of the SiO2. Results from DSDP in the nodule area suggest that metalliferous globules are a ubiquitous minor component of the Clipperton Oceanic Formation, which underlies much of the Pacific ferromanganese nodule belt. This indicates that deposition of hydrothermal precipitates is not confined to spreading centers. ?? 1977.

Compact-Morphology-based poly-metallic Nodule Delineation.

Science.gov (United States)

Schoening, Timm; Jones, Daniel O B; Greinert, Jens

2017-10-17

Poly-metallic nodules are a marine resource considered for deep sea mining. Assessing nodule abundance is of interest for mining companies and to monitor potential environmental impact. Optical seafloor imaging allows quantifying poly-metallic nodule abundance at spatial scales from centimetres to square kilometres. Towed cameras and diving robots acquire high-resolution imagery that allow detecting individual nodules and measure their sizes. Spatial abundance statistics can be computed from these size measurements, providing e.g. seafloor coverage in percent and the nodule size distribution. Detecting nodules requires segmentation of nodule pixels from pixels showing sediment background. Semi-supervised pattern recognition has been proposed to automate this task. Existing nodule segmentation algorithms employ machine learning that trains a classifier to segment the nodules in a high-dimensional feature space. Here, a rapid nodule segmentation algorithm is presented. It omits computation-intense feature-based classification and employs image processing only. It exploits a nodule compactness heuristic to delineate individual nodules. Complex machine learning methods are avoided to keep the algorithm simple and fast. The algorithm has successfully been applied to different image datasets. These data sets were acquired by different cameras, camera platforms and in varying illumination conditions. Their successful analysis shows the broad applicability of the proposed method.

Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

International Nuclear Information System (INIS)

Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

2011-01-01

Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes.

Science.gov (United States)

Aydin, Sibel Zehra; Can, Meryem; Alibaz-Oner, Fatma; Keser, Gokhan; Kurum, Esra; Inal, Vedat; Yazisiz, Veli; Birlik, Merih; Emmungil, Hakan; Atagunduz, Pamir; Direskeneli, Haner; McGonagle, Dennis; Pay, Salih

2016-03-01

Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (ρ = 0.274, p gender-specific phenotype that could be a useful marker predicting of new bone formation.

Effect of Cytokines on Osteoclast Formation and Bone Resorption during Mechanical Force Loading of the Periodontal Membrane

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Hideki Kitaura

2014-01-01

Full Text Available Mechanical force loading exerts important effects on the skeleton by controlling bone mass and strength. Several in vivo experimental models evaluating the effects of mechanical loading on bone metabolism have been reported. Orthodontic tooth movement is a useful model for understanding the mechanism of bone remodeling induced by mechanical loading. In a mouse model of orthodontic tooth movement, TNF-α was expressed and osteoclasts appeared on the compressed side of the periodontal ligament. In TNF-receptor-deficient mice, there was less tooth movement and osteoclast numbers were lower than in wild-type mice. These results suggest that osteoclast formation and bone resorption caused by loading forces on the periodontal ligament depend on TNF-α. Several cytokines are expressed in the periodontal ligament during orthodontic tooth movement. Studies have found that inflammatory cytokines such as IL-12 and IFN-γ strongly inhibit osteoclast formation and tooth movement. Blocking macrophage colony-stimulating factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth movement. In this review we describe and discuss the effect of cytokines in the periodontal ligament on osteoclast formation and bone resorption during mechanical force loading.

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

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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

Quantification of the Volume and Surface Area of Symbiosomes and Vacuoles of Infected Cells in Root Nodules of Medicago truncatula

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Gavrin, A.Y.; Fedorova, E.

2015-01-01

Legumes are able to form endosymbiotic interactions with nitrogen-fixing rhizobia. Endosymbiosis takes shape in formation of a symbiotic organ, the root nodule. Medicago truncatula (M. truncatula) nodules contain several zones representing subsequent stages of development. The apical part of the

Homology of genes for exopolysaccharide synthesis in Rhizobium leguminosarum and effect of cloned exo genes on nodule formation

International Nuclear Information System (INIS)

Skorupska, A.; Derylo, M.

1993-01-01

A 5.4 kb BamHI fragment of Rhizobium leguminosarum (R.l.) bv. trifolii TA1 was found to carry genes involved in exopolysaccharide synthesis (exo genes). This fragment was strongly hybridized to the total DNA from DNA from R.l. bv. viciae and bv. phaseoli digested with EcoRI. No homology was found with total DNA of R. melilotic and Rhizobium sp. NGR 234. The exo genes R.l. bv. trifolii TA1 conjugally introduced into R.l. bv. viciae 1302 considerably affected the symbiosis: the nodules induced on vetch were abortive and did not fix nitrogen. On the other hand, Phaseolus beans infected with R.l. bv. trifolii exo genes formed the nitrogen-fixing nodules. It can be conduced that additional copies of exo genes introduced into wild type R.l. strains can disturb the synthesis of acidic exopolysaccharides and affect symbiosis of the plants forming indeterminate nodules, but do not affect symbiosis of the plants forming the determinate nodules. (author). 29 refs, 2 figs, 2 tabs

Do manganese nodules grow or dissolve after burial? Results from the Central Indian Ocean Basin

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Pattan, J. N.; Parthiban, G.

2007-07-01

Fifty buried manganese nodules at different depth intervals were recovered in 12 sediment cores from the Central Indian Ocean Basin (CIOB). A maximum of 15 buried nodules were encountered in one sediment core (AAS-22/GC-07) and the deepest nodule was recovered at 5.50 m below seafloor in core AAS-04/GC-5A. Approximately 80% of the buried nodules are small in size (˜2 cm diameter) in contrast to the Atlantic Ocean and Peru Basin (Pacific Ocean) where the majority of the buried nodules are large, ˜8 cm and >6 cm, respectively. Buried nodule size decreases with core depth and this distribution appears to be similar to the phenomenon of "Brazil Nut Effect". Buried nodules exhibit both smooth and rough surface textures and are ellipsoidal, elongated, rounded, sub rounded, irregular and polynucleated. Buried nodules from siliceous ooze are enriched in Mn, Cu, Ni, Zn, Mo, Ga, V and Rb whereas those from red clay are enriched in Fe, Co, Ti, U, Th, Y, Cr, Nb and Rare Earth Elements (REE). Buried nodules from siliceous ooze suggest their formation under hydrogenetic, early digenetic and diagenetic processes whereas those from red clay are of hydrogenetic origin. REE are enriched more than 1.5 times in buried nodules from red clay compared to siliceous ooze. However, the mode of incorporation of REE into buried nodules from both sedimentary environments is by a single authigenic phase consisting of Fe-Ti-P. Shale-normalized REE patterns and Ce anomalies suggest that nodules from siliceous ooze formed under more oxidizing conditions than those from red clay. Nodules buried at depths between 1.5 and 2.5 m are diagenetic (Mn/Fe ratio 10-15), formed in highly oxic environments (large positive Ce anomalies) and record aeolian dust (high Eu anomalies). Chemical composition, surface texture and morphology of buried nodules are similar to those of surface nodules from the same basin. Furthermore, buried nodule compositions do not exhibit any distinct patterns within the core depth

Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

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Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

2014-10-01

Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (pBone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (pbone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Critical metals in manganese nodules from the Cook Islands EEZ, abundances and distributions

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Hein, James R.; Spinardi, Francesca; Okamoto, Nobuyuki; Mizell, Kira; Thorburn, Darryl; Tawake, Akuila

2015-01-01

The Cook Islands (CIs) Exclusive Economic Zone (EEZ) encompasses 1,977,000 km2 and includes the Penrhyn and Samoa basins abyssal plains where manganese nodules flourish due to the availability of prolific nucleus material, slow sedimentation rates, and strong bottom currents. A group of CIs nodules was analyzed for mineralogical and chemical composition, which include many critical metals not before analyzed for CIs nodules. These nodules have varying sizes and nuclei material; however all are composed predominantly of δ-MnO2 and X-ray amorphous iron oxyhydroxide. The mineralogy, Fe/Mn ratios, rare earth element contents, and slow growth rates (mean 1.9 mm/106 years) reflect formation primarily by hydrogenetic precipitation. The paucity of diagenetic input can be explained by low primary productivity at the surface and resultant low organic matter content in seafloor sediment, producing oxic seafloor and sub-seafloor environments. The nodules contain high mean contents of Co (0.41%), Ni (0.38%), Ti (1.20%), and total rare earth elements plus yttrium (REY; 0.167%), and also high contents of Mo, Nb, V, W, and Zr.

Thyroid Nodule Imaging. Status and Limitations.

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Durre Sabih

2015-01-01

Full Text Available Thyroid nodules are common, occurring in almost two-thirds of some populations; among these only about 7% are malignant. The most important question with any new discovered thyroid nodule is, “is this malignant?” The main arbiter of malignancy or benignity remains fine needle aspiration and the mainstay of treatment surgery. But given the resources involved, doing an FNAC or surgery in every discovered nodule would be prohibitive to impossible. The clinician must decide which nodule to investigate and which to watch in the hope that this will never turn out to be malignant. FNACs are used basically to decide which nodule to operate upon (or more importantly which to not operate upon and clinical and imaging features are used to decide which nodule to investigate by FNAC and which to leave alone. This paper describes the various imaging options for looking at thyroid nodules and briefly discusses the advantages and disadvantages with each.

Detection of small pulmonary nodules on chest radiographs: efficacy of dual-energy subtraction technique using flat-panel detector chest radiography

International Nuclear Information System (INIS)

Oda, S.; Awai, K.; Funama, Y.; Utsunomiya, D.; Yanaga, Y.; Kawanaka, K.; Nakaura, T.; Hirai, T.; Murakami, R.; Nomori, H.; Yamashita, Y.

2010-01-01

Aim: To investigate the effect of a double-exposure dual-energy subtraction (DES) technique on the diagnostic performance of radiologists detecting small pulmonary nodules on flat-panel detector (FPD) chest radiographs. Materials and methods: Using FPD radiography 41 sets of chest radiographs were obtained from 26 patients with pulmonary nodules measuring ≤20 mm and from 15 normal participants. Each dataset included standard and corresponding DES images. There were six non-solid, 10 part-solid, and 10 solid nodules. The mean size of the 26 nodules was 15 ± 4.8 mm. Receiver operating characteristic (ROC) analysis was performed to compare the performance of the eight board-certified radiologists. Results: For the eight radiologists, the mean value of the area under the ROC curve (AUC) without and with DES images was 0.62 ± 0.05 and 0.68 ± 0.05, respectively; the difference was statistically significant (p = 0.02). For part-solid nodules, the difference of the mean AUC value was statistically significant (AUC = 0.61 ± 0.07 versus 0.69 ± 0.05; p < 0.01); for non-solid nodules it was not (AUC = 0.62 ± 0.1 versus 0.61 ± 0.09; p = 0.73), and for solid nodules it was not (AUC = 0.75 ± 0.1 versus 0.78 ± 0.08; p = 0.23). For nodules with overlapping bone shadows, the difference of the mean AUC value was statistically significant (p = 0.03), for nodules without overlapping, it was not (p = 0.26). Conclusion: Use of a double-exposure DES technique at FPD chest radiography significantly improved the diagnostic performance of radiologists to detect small pulmonary nodules.

Differential Regulation of the Nodulation Zone by Silver Ions, L--(2-Amino-Ethoxyvinyl-Glycine, and the skl Mutation in Medicago truncatula

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JOKO PRAYITNO

2010-03-01

Full Text Available Nodule formation in Rhizobium-legume symbiosis is negatively regulated by ethylene. Ethylene inhibitors such as L--(2-amino-ethoxyvinyl-glycine (AVG and silver ions (Ag+, the ethylene-insensitive sickle mutant, and transgenic plants were used to study ethylene-mediated responses in nodulation. The mode of action of ethylene inhibitors AVG and Ag+, and the skl mutation occur at different steps in ethylene biosynthesis and perception. Their effects on root growth and nodulation phenotypes, in particular nodule distribution along the primary root, were compared in this study. Ag+ and AVG treatments showed similar root growth responses to skl mutant. However, nodule distribution in the hypernodulating skl mutant is different from that of wild-type plants grown on either AVG or Ag+. AVG increased nodule numbers and widened the nodulation zone, while the skl mutant had an increased number of nodules within the susceptible zone of nodulation. Ag+ reduced nodule numbers, restricted the nodulation zone, and restored the nodulation phenotype of skl to that of the wild type.

Bone formation within a breast abscess.

Science.gov (United States)

Mannu, Gurdeep Singh; Ahmed, Farid; Cunnick, Giles; Mungalsingh, Naren

2014-09-22

We present a rare case of osseous metaplasia in a poorly healing breast abscess. An 87-year-old woman was referred to the breast surgery clinic with a painful lump in her right breast. Initial imaging and core biopsy suggested a breast abscess. Despite several courses of antibiotics and repeated attempts at aspiration the painful lesion persisted. It was eventually surgically excised in its entirety and final histopathology showed the presence of bone formation within the abscess. The patient's symptoms subsequently resolved. To the best of our knowledge, this is the first case in the literature, of osseous metaplasia within a breast abscess in the absence of malignancy. 2014 BMJ Publishing Group Ltd.

Management of an incidentally discovered pulmonary nodule

International Nuclear Information System (INIS)

Beigelman-Aubry, Catherine; Hill, Catherine; Grenier, Philippe A.

2007-01-01

The incidental finding of a pulmonary nodule on computed tomography (CT) is becoming an increasingly frequent event. The discovery of such a nodule should evoke the possibility of a small bronchogenic carcinoma, for which excision is indicated without delay. However, invasive diagnostic procedures should be avoided in the case of a benign lesion. The objectives of this review article are: (1) to analyze the CT criteria defining benign nodules, nodules of high suspicion of malignancy and indeterminate nodules, (2) to analyze the diagnostic performances and limitations of complementary investigations requested to characterize indeterminate lung nodules, (3) to review the criteria permitting to assess the probability of malignancy of indeterminate nodules and (4) to report on the new guidelines provided by the Fleischner Society for the management of small indeterminate pulmonary nodules, according to their prior probability of malignancy. (orig.)

Beneath the Minerals, a Layer of Round Lipid Particles Was Identified to Mediate Collagen Calcification in Compact Bone Formation

OpenAIRE

Xu, Shaohua; Yu, Jianqing J.

2006-01-01

Astronauts lose 1–2% of their bone minerals per month during space flights. A systematic search for a countermeasure relies on a good understanding of the mechanism of bone formation at the molecular level. How collagen fibers, the dominant matrix protein in bones, are mineralized remains mysterious. Atomic force microscopy was carried out, in combination with immunostaining and Western blotting, on bovine tibia to identify unrecognized building blocks involved in bone formation and for an el...

Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.

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April S Chan

2009-11-01

Full Text Available The bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these interactions are just beginning to be characterized.An Id1(-/- mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1(-/- mice have reduced bone mass and increased bone fragility, consistent with an osteoporotic phenotype. Osteoclastogenesis and pit formation assays revealed that loss of Id1 increased osteoclast differentiation and resorption activity, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Examination by flow cytometry of the hematopoietic compartment of Id1(-/- mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id1(-/- bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1(-/- mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice.In conclusion, we demonstrate an osteoporotic phenotype in Id1(-/- mice and a mechanism for Id1 transcriptional control of osteoclast-associated genes. Our results identify Id1 as a principal player responsible for the dynamic cross-talk between bone and bone marrow hematopoietic cells.

Bone Formation Following Sinus Augmentation with an Equine-Derived Bone Graft: A Retrospective Histologic and Histomorphometric Study with 36-Month Follow-up.

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Di Stefano, Danilo Alessio; Gastaldi, Giorgio; Vinci, Raffaele; Polizzi, Elisabetta Maria; Cinci, Lorenzo; Pieri, Laura; Gherlone, Enrico

2016-01-01

The aim of this study was to investigate bone formation over time following maxillary sinus augmentation with an enzyme-deantigenic, bone collagen-preserving equine bone graft by retrospective assessment of histomorphometric data. Records of patients with atrophic ridges who underwent maxillary sinus augmentation with the enzyme-deantigenic equine bone graft and two-step implant placement between 3 and 12 months after the sinus-augmentation surgery were assessed retrospectively. The histomorphometric data were clustered in three classes according to time of collection from the augmentation surgery and analyzed to assess newly formed bone deposition and residual biomaterial degradation rates. Data concerning the 36-month clinical follow-up were also assessed. Records of 77 patients and 115 biopsy specimens were retrieved, and histomorphometric data were clustered (3 to 5 months, n = 33; 6 to 8 months, n = 57; 9 to 12 months, n = 25). Mean minimum atrophic ridge thickness was 4.9 ± 0.5 mm (range, 4.0 to 7.1 mm). The amount of newly formed bone and residual biomaterial did not significantly differ among the three clusters. Qualitative analysis showed a denser trabecular structure in late (> 8 months) samples. At the 36-month clinical follow-up, no differences were found among the implant success rates in the three groups, according to the Albrektsson and Zarb criteria for success. The overall implant success rate was 98.3%. Based upon this retrospective human study of 77 patients with 4 to 7 mm of residual bone, when enzyme-deantigenic equine bone is used for sinus augmentation, new bone formation occurs at an early time (augmentation surgery.

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

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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

Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic rhBMP-2 and anti-resorptive agents

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NYC Yu

2014-01-01

Full Text Available 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 < 0.01. The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01. Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01. Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation.

Expression of nodule-specific genes in alfalfa root nodules blocked at an early stage of development.

NARCIS (Netherlands)

Dickstein, R.; Bisseling, T.; Reinhold, V.N.; Ausubel, F.M.

1988-01-01

To help dissect the molecular basis of the Rhizobium-legume symbiosis, we used in vitro translation and Northern blot analysis of nodule RNA to examine alfalfa-specific genes (nodulins) expressed in two types of developmentally defective root nodules elicited by Rhizobium meliloti. Fix- nodules were

Inflammation Intensity-dependent Expression of Osteoinductive Wnt Proteins is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis.

Science.gov (United States)

Li, Xiang; Wang, Jianru; Zhan, Zhongping; Li, Sibei; Zheng, Zhaomin; Wang, Taiping; Zhang, Kuibo; Pan, Hehai; Li, Zemin; Zhang, Nu; Liu, Hui

2018-02-26

To investigate the molecular mechanism underlying the inflammation- related ectopic new bone formation in ankylosing spondylitis (AS). Spinal tissues and sera were collected from patients or normal volunteers to detect the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression and the role of Wnt signaling in new bone formation. A modified collagen-induced arthritis (mCIA) and a proteoglycan -induced spondylitis (PGIS) animal model were used to confirm the key findings in vivo. The levels of osteoinductive Wnt proteins were obviously increased in the sera and spinal ligament tissues of patients with AS. Only constitutive low-intensity TNF-α stimulation, but not short-term or high-intensity TNF-α stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF-κB (p65) and JNK/AP-1 (c-Jun) signaling pathways. Furthermore, inhibition of either Wnt/β-catenin or Wnt/PKCδ pathway significantly suppressed new bone formation. The increased expression of Wnt proteins was confirmed in both mCIA and PGIS models. A kyphotic and ankylosing phenotype of the spine was observed during long-term observation in mCIA model. Inhibition of either Wnt/β-catenin or Wnt/PKCδ signaling pathway significantly reduced the incidence and severity of this phenotype. Inflammation intensity-dependent expression of osteoinductive Wnt proteins is a key link between inflammation and ectopic new bone formation in AS. Activation of both canonical Wnt/β-catenin and noncanonical Wnt/PKCδ pathways is required for inflammation-induced new bone formation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects of loading methods on bone marrow stromal cell differentiation in vivo and in vitro.

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Tsuchiya, Shuhei; Sugimoto, Keisuke; Kamio, Hisanobu; Okabe, Kazuto; Kuroda, Kensuke; Okido, Masazumi; Hibi, Hideharu

2018-01-01

Surface modification of titanium dioxide (TiO 2 ) implants promotes bone formation and shortens the osseointegration period. Kaempferol is a flavonoid that has the capacity to promote osteogenic differentiation in bone marrow stromal cells. The aim of this study was to promote bone formation around kaempferol immobilized on TiO 2 implants. There were four experimental groups. Alkali-treated TiO 2 samples (implants and discs) were used as a control and immersed in Dulbecco's phosphate-buffered saline (DPBS) (Al-Ti). For the coprecipitation sample (Al-cK), the control samples were immersed in DPBS containing 50 µg kaempferol/100% ethanol. For the adsorption sample (Al-aK), 50 µg kaempferol/100% ethanol was dropped onto control samples. The surface topography of the TiO 2 implants was observed by scanning electron microscopy with energy-dispersive X-ray spectroscopy, and a release assay was performed. For in vitro experiments, rat bone marrow stromal cells (rBMSCs) were cultured on each of the TiO 2 samples to analyze cell proliferation, alkaline phosphatase activity, calcium deposition, and osteogenic differentiation. For in vivo experiments, TiO 2 implants placed on rat femur bones were analyzed for bone-implant contact by histological methods. Kaempferol was detected on the surface of Al-cK and Al-aK. The results of the in vitro study showed that rBMSCs cultured on Al-cK and Al-aK promoted alkaline phosphatase activity, calcium deposition, and osteogenic differentiation. The in vivo histological analysis revealed that Al-cK and Al-aK stimulated new bone formation around implants. TiO 2 implant-immobilized kaempferol may be an effective tool for bone regeneration around dental implants.

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

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.

Exercise-induced bone formation is poorly linked to local strain magnitude in the sheep tibia.

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Ian J Wallace

Full Text Available Functional interpretations of limb bone structure frequently assume that diaphyses adjust their shape by adding bone primarily across the plane in which they are habitually loaded in order to minimize loading-induced strains. Here, to test this hypothesis, we characterize the in vivo strain environment of the sheep tibial midshaft during treadmill exercise and examine whether this activity promotes bone formation disproportionately in the direction of loading in diaphyseal regions that experience the highest strains. It is shown that during treadmill exercise, sheep tibiae were bent in an anteroposterior direction, generating maximal tensile and compressive strains on the anterior and posterior shaft surfaces, respectively. Exercise led to significantly increased periosteal bone formation; however, rather than being biased toward areas of maximal strains across the anteroposterior axis, exercise-related osteogenesis occurred primarily around the medial half of the shaft circumference, in both high and low strain regions. Overall, the results of this study demonstrate that loading-induced bone growth is not closely linked to local strain magnitude in every instance. Therefore, caution is necessary when bone shaft shape is used to infer functional loading history in the absence of in vivo data on how bones are loaded and how they actually respond to loading.

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

Science.gov (United States)

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

The MicroRNA390/TAS3 Pathway Mediates Symbiotic Nodulation and Lateral Root Growth1[OPEN

Science.gov (United States)

Bustos-Sanmamed, Pilar; Mysore, Kirankumar S.

2017-01-01

Legume roots form two types of postembryonic organs, lateral roots and symbiotic nodules. Nodule formation is the result of the interaction of legumes with rhizobia and requires the mitotic activation and differentiation of root cells as well as an independent, but coordinated, program that allows infection by rhizobia. MicroRNA390 (miR390) is an evolutionarily conserved microRNA that targets the Trans-Acting Short Interference RNA3 (TAS3) transcript. Cleavage of TAS3 by ARGONAUTE7 results in the production of trans-acting small interference RNAs, which target mRNAs encoding AUXIN RESPONSE FACTOR2 (ARF2), ARF3, and ARF4. Here, we show that activation of the miR390/TAS3 regulatory module by overexpression of miR390 in Medicago truncatula promotes lateral root growth but prevents nodule organogenesis, rhizobial infection, and the induction of two key nodulation genes, Nodulation Signaling Pathway1 (NSP1) and NSP2. Accordingly, inactivation of the miR390/TAS3 module, either by expression of a miR390 target mimicry construct or mutations in ARGONAUTE7, enhances nodulation and rhizobial infection, alters the spatial distribution of the nodules, and increases the percentage of nodules with multiple meristems. Our results revealed a key role of the miR390/TAS3 pathway in legumes as a modulator of lateral root organs, playing opposite roles in lateral root and nodule development. PMID:28663332

New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study.

Science.gov (United States)

Lee, Jin Whan; Wen, Hai Bo; Gubbi, Prabhu; Romanos, Georgios E

2018-02-01

This study evaluated new bone formation activities and trabecular bone microarchitecture within the highly porous region of Trabecular Metal™ Dental Implants (TM) and between the threads of Tapered Screw-Vent® Dental Implants (TSV) in fresh canine extraction sockets. Eight partially edentulated dogs received four implants (4.1 mmD × 13 mmL) bilaterally in mandibular fresh extraction sockets (32 TM, 32 TSV implants), and allowed to heal for 2, 4, 8, and 12 weeks. Calcein was administered to label mineralizing bone at 11 and 4 days before euthanasia for dogs undergoing all four healing periods. Biopsies taken at each time interval were examined histologically. Histomorphometric assay was conducted for 64 unstained and 64 stained slides at the region of interest (ROI) (6 mm long × 0.35 mm deep) in the midsections of the implants. Topographical and chemical analyses were also performed. Histomorphometry revealed significantly more new bone in the TM than in the TSV implants at each healing time (p = .0014, .0084, .0218, and .0251). Calcein-labeled data showed more newly mineralized bone in the TM group than in the TSV group at 2, 8, and 12 weeks (p = .045, .028, .002, respectively) but not at 4 weeks (p = .081). Histologically TM implants exhibited more bone growth and dominant new immature woven bone at an earlier time point than TSV implants. The parameters representing trabecular bone microarchitecture corroborated faster new bone formation in the TM implants when compared to the TSV implants. TM exhibited an irregular faceted topography compared to a relatively uniform microtextured surface for TSV. Chemical analysis showed peaks associated with each implant's composition material, and TSV also showed peaks reflecting the elements of the calcium phosphate blasting media. Results suggest that the healing pathway associated with the highly porous midsection of TM dental implant could enable faster and stronger secondary implant stability than

Effects of irradiation on TGF-β1 mRNA expression and calcific nodule formation in MC3T3-E1 osteoblastic cell line

International Nuclear Information System (INIS)

Song, Ju Seop; Kim, Kyoung A; Koh, Kwang Joon

2008-01-01

To investigate the effects of irradiation on transforming growth factor β1 (TGF-β 1 ) mRNA expression and calcific nodule formation in MC3T3-E1 osteoblastic cell line. Cells were cultured in alpha-minimum essential medium (α-MEM) supplemented with 10% fetal bovine serum and antibiotics. When the cells reached the level of 70-80% confluence, culture media were changed with α-MEM supplemented with 10% FBS, 5 mM β-glycerol phosphate, and 50 μg/mL ascorbic acid. Thereafter the cells were irradiated with a single dose of 2, 4, 6, 8 Gy at a dose rate of 1.5 Gy/min. The expression pattern of TGF-β 1 mRNA, calcium content and calcific nodule formation were examined on day 3, 7, 14, 21, 28, respectively, after the irradiation. The amount of TGF-β 1 mRNA expression decreased significantly on day 7 after irradiation of 4, 6, 8 Gy. It also decreased on day 14 after irradiation of 6, 8 Gy, and decreased on day 21 after irradiation of 8 Gy. The amount of calcium deposition decreased significantly on day 7 after irradiation of 4, 8 Gy (P 1 mRNA expression that was associated with proliferation and the production of extracellular matrix in MC3T3-E1 osteoblastic cell line

A comprehensive view of manganese nodules and volcanics of the Central Indian Ocean Basin

Digital Repository Service at National Institute of Oceanography (India)

Jauhari, P.; Iyer, S.D.

the seafloor. Various theories have been proposed to explain the enigma of heavier nodules resting on lighter sediments especially when the rate of sediment accumu- lation is higher than the growth of the nodules. Glasby and Read (1976) observed that due... silicic erup- tion and pumice formation. Moreover, it has been reported that hot pumice sinks faster, due to a greater capacity to absorb water and being nearer to the source as compared to colder pumice (Whitham and Sparks, 1986). We presume...

Relation between nodule size and 18F-FDG-PET SUV for malignant and benign pulmonary nodules.

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Shao Yiping

2008-09-01

Full Text Available Abstract The most common semiquantitative method of evaluation of pulmonary lesions using 18F-FDG PET is FDG standardized uptake value (SUV. An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules. Methods Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUVmax for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUVmax cutoff of 2.5. Results The linear regression equations and (R2s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm are plotted in a dot diagram using an SUVmax cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUVmax cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1–2.0 cm; 94%, 23%, and 76%, respectively for group 3 (2.1–3.0 cm; and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm. The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUVmax cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules. Conclusion The slope of the regression line is greater for malignant than for benign nodules. Although, the SUVmax cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm, it has no or minimal value in the evaluation of small

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

Science.gov (United States)

Ding, Ming; Henriksen, Susan S; Martinetti, Roberta; Overgaard, Søren

2017-11-01

Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. © 2016 Wiley Periodicals, Inc.

Performance of computer-aided detection of pulmonary nodules in low-dose CT: comparison with double reading by nodule volume

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Zhao, Yingru; Vliegenthart, Rozemarijn; Wang, Ying; Ooijen, Peter M.A. van; Oudkerk, Matthijs [University of Groningen/University Medical Center Groningen, Center for Medical Imaging - North East Netherlands, Department of Radiology, P.O. Box 30.001, Groningen (Netherlands); Bock, Geertruida H. de [University of Groningen/University Medical Center Groningen, Department of Epidemiology, P.O. Box 30.001, Groningen (Netherlands); Klaveren, Rob J. van [Lievensberg Hospital, Department of Pulmonology, P.O. Box 135, Bergen op Zoom (Netherlands); Bogoni, Luca [CAD Group, Siemens Medical Solutions USA, Inc., Malvern, PA (United States); Jong, Pim A. de; Mali, Willem P. [University of Utrecht, Department of Radiology, University Medical Center Utrecht, P.O. Box 85500, Utrecht (Netherlands)

2012-10-15

To evaluate performance of computer-aided detection (CAD) beyond double reading for pulmonary nodules on low-dose computed tomography (CT) by nodule volume. A total of 400 low-dose chest CT examinations were randomly selected from the NELSON lung cancer screening trial. CTs were evaluated by two independent readers and processed by CAD. A total of 1,667 findings marked by readers and/or CAD were evaluated by a consensus panel of expert chest radiologists. Performance was evaluated by calculating sensitivity of pulmonary nodule detection and number of false positives, by nodule characteristics and volume. According to the screening protocol, 90.9 % of the findings could be excluded from further evaluation, 49.2 % being small nodules (less than 50 mm{sup 3}). Excluding small nodules reduced false-positive detections by CAD from 3.7 to 1.9 per examination. Of 151 findings that needed further evaluation, 33 (21.9 %) were detected by CAD only, one of them being diagnosed as lung cancer the following year. The sensitivity of nodule detection was 78.1 % for double reading and 96.7 % for CAD. A total of 69.7 % of nodules undetected by readers were attached nodules of which 78.3 % were vessel-attached. CAD is valuable in lung cancer screening to improve sensitivity of pulmonary nodule detection beyond double reading, at a low false-positive rate when excluding small nodules. circle Computer-aided detection (CAD) has known advantages for computed tomography (CT). (orig.)

Performance of computer-aided detection of pulmonary nodules in low-dose CT: comparison with double reading by nodule volume

International Nuclear Information System (INIS)

Zhao, Yingru; Vliegenthart, Rozemarijn; Wang, Ying; Ooijen, Peter M.A. van; Oudkerk, Matthijs; Bock, Geertruida H. de; Klaveren, Rob J. van; Bogoni, Luca; Jong, Pim A. de; Mali, Willem P.

2012-01-01

To evaluate performance of computer-aided detection (CAD) beyond double reading for pulmonary nodules on low-dose computed tomography (CT) by nodule volume. A total of 400 low-dose chest CT examinations were randomly selected from the NELSON lung cancer screening trial. CTs were evaluated by two independent readers and processed by CAD. A total of 1,667 findings marked by readers and/or CAD were evaluated by a consensus panel of expert chest radiologists. Performance was evaluated by calculating sensitivity of pulmonary nodule detection and number of false positives, by nodule characteristics and volume. According to the screening protocol, 90.9 % of the findings could be excluded from further evaluation, 49.2 % being small nodules (less than 50 mm 3 ). Excluding small nodules reduced false-positive detections by CAD from 3.7 to 1.9 per examination. Of 151 findings that needed further evaluation, 33 (21.9 %) were detected by CAD only, one of them being diagnosed as lung cancer the following year. The sensitivity of nodule detection was 78.1 % for double reading and 96.7 % for CAD. A total of 69.7 % of nodules undetected by readers were attached nodules of which 78.3 % were vessel-attached. CAD is valuable in lung cancer screening to improve sensitivity of pulmonary nodule detection beyond double reading, at a low false-positive rate when excluding small nodules. circle Computer-aided detection (CAD) has known advantages for computed tomography (CT). (orig.)

Diagnosis and management of solitary pulmonary nodules.

Science.gov (United States)

Jeong, Yeon Joo; Lee, Kyung Soo; Kwon, O Jung

2008-12-01

The advent of computed tomography (CT) screening with or without the help of computer-aided detection systems has increased the detection rate of solitary pulmonary nodules (SPNs), including that of early peripheral lung cancer. Helical dynamic (HD)CT, providing the information on morphologic and hemodynamic characteristics with high specificity and reasonably high accuracy, can be used for the initial assessment of SPNs. (18)F-fluorodeoxyglucose PET/CT is more sensitive at detecting malignancy than HDCT. Therefore, PET/CT may be selectively performed to characterize SPNs when HDCT gives an inconclusive diagnosis. Serial volume measurements are currently the most reliable methods for the tissue characterization of subcentimeter nodules. When malignant nodule is highly suspected for subcentimeter nodules, video-assisted thoracoscopic surgery nodule removal after nodule localization using the pulmonary nodule-marker system may be performed for diagnosis and treatment.

Evidence for Ongoing Modeling-Based Bone Formation in Human Femoral Head Trabeculae via Forming Minimodeling Structures: A Study in Patients with Fractures and Arthritis.

Science.gov (United States)

Sano, Hiroshige; Kondo, Naoki; Shimakura, Taketoshi; Fujisawa, Junichi; Kijima, Yasufumi; Kanai, Tomotake; Poole, Kenneth E S; Yamamoto, Noriaki; Takahashi, Hideaki E; Endo, Naoto

2018-01-01

Bone modeling is a biological process of bone formation that adapts bone size and shape to mechanical loads, especially during childhood and adolescence. Bone modeling in cortical bone can be easily detected using sequential radiographic images, while its assessment in trabecular bone is challenging. Here, we performed histomorphometric analysis in 21 bone specimens from biopsies collected during hip arthroplasty, and we proposed the criteria for histologically identifying an active modeling-based bone formation, which we call a "forming minimodeling structure" (FMiS). Evidence of FMiSs was found in 9 of 20 specimens (45%). In histomorphometric analysis, bone volume was significant higher in specimens displaying FMiSs compared with the specimens without these structures (BV/TV, 31.7 ± 10.2 vs. 23.1 ± 3.9%; p  modeling-based bone formation on trabecular bone surfaces occurs even during adulthood. As FMiSs can represent histological evidence of modeling-based bone formation, understanding of this physiology in relation to bone homeostasis is crucial.

Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM.

Science.gov (United States)

Lewin, S; Barba, A; Persson, C; Franch, J; Ginebra, M-P; Öhman-Mägi, C

2017-10-05

There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (μCT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in μCT images. Commonly, segmentation of bone in μCT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by μCT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. μCT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the μCT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

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Jodi A. Carlson Scholz

2012-12-01

Full Text Available Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH. Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

Comparison of the nodule vs. root transcriptome of the actinorhizal plant Datisca glomerata: actinorhizal nodules contain a specific class of defensins.

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Irina V Demina

Full Text Available Actinorhizal root nodule symbioses are very diverse, and the symbiosis of Datisca glomerata has previously been shown to have many unusual aspects. In order to gain molecular information on the infection mechanism, nodule development and nodule metabolism, we compared the transcriptomes of D. glomerata roots and nodules. Root and nodule libraries representing the 3'-ends of cDNAs were subjected to high-throughput parallel 454 sequencing. To identify the corresponding genes and to improve the assembly, Illumina sequencing of the nodule transcriptome was performed as well. The evaluation revealed 406 differentially regulated genes, 295 of which (72.7% could be assigned a function based on homology. Analysis of the nodule transcriptome showed that genes encoding components of the common symbiosis signaling pathway were present in nodules of D. glomerata, which in combination with the previously established function of SymRK in D. glomerata nodulation suggests that this pathway is also active in actinorhizal Cucurbitales. Furthermore, comparison of the D. glomerata nodule transcriptome with nodule transcriptomes from actinorhizal Fagales revealed a new subgroup of nodule-specific defensins that might play a role specific to actinorhizal symbioses. The D. glomerata members of this defensin subgroup contain an acidic C-terminal domain that was never found in plant defensins before.

Telomerase reverse transcriptase mediated immortalization of human bone marrow stromal cells

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Yong Teng

2014-02-01

Full Text Available Primary human bone marrow stromal cells (hMSCs were transfected with human telomerase reverse transcriptase (hTERT gene with lipofection method. The hTERT transfected hMSCs of passage 100 underwent chondrogenesis induction with dexamethasone, transforming the growth factor β and vitamin C, osteogenesis induction with dexamethasone, β glycerophosphoric acid and vitamin C, and cardiomyocyte induction with 5-azacytidine. After 7, 14, 21 and 28 days of induction, immunocytochemistry was performed to detect the expressions of type I and II collagen and osteocalcin, and alizarin red staining was performed to detect the bone nodule formation in osteogenesis induction. Immunocytochemistry was carried out to detect the striated muscle actin expression in cardiomyocytes. The hMSCs undergoing successful transfection were positive for the hTERT. The hTERT transfected cells were grown in vitro successfully and passaged for 136 generations. Results showed that these cells could be induced to differentiate into chondrocytes, bone and myocardial cells. Introduction of exogenous hTERT into hMSCs could achieve immortalized hMSCs with the potential of multi-directional differentiation. Thus, these cells could be applied as seed cells in tissue engineering.

A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation

DEFF Research Database (Denmark)

Thudium, Christian S; Moscatelli, Ilana; Flores, Carmen

2014-01-01

that osteoclasts are important for regulating osteoblast activity. To illuminate the role of the osteoclast in controlling bone remodeling, we transplanted irradiated skeletally mature 3-month old wild-type mice with hematopoietic stem cells (HSCs) to generate either an osteoclast-rich or osteoclast-poor adult......Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating...... osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In contrast, the bone...

Calcium citrate: a new biomaterial that can enhance bone formation in situ

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WANG Li-ming

2012-11-01

Full Text Available 【Abstract】 Objective: To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2 on bone regeneration in a bone defect rabbit model. Methods: Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2 group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respec-tively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg combined with rhBMP-2 (2 mg or rhBMP-2 alone were im-planted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis. Results: Histomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%±1.26% vs 48.21%±2.37% at 2 weeks; 43.40%±1.65% vs 57.32%±1.47% at 4 weeks, and 51.32%±7.80% vs 66.74%±4.05% at 6 weeks (P<0.05 for all. At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group. Conclusion: From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly en-hances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions. Key words: Bone morphogenetic protein-2; Biocompatible materials; Calcium citrate; Gelatin

Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report

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Luca Guarda-Nardini

2014-04-01

Full Text Available Background: The literature on total alloplastic temporomandibular joint (TMJ reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular joint prosthesis, which occurred several years after the implant. Methods: The present manuscript describes a case of heterotopic bone formation around a total TMJ prosthesis, which occurred several years after the implant in patients, who previously underwent multiple failed TMJ surgeries. Results: Ten years after the surgical TMJ replacement to solve an ankylotic bone block, the patient came to our attention again referring a progressive limitation in mouth opening. A computerized tomography showed evidence of marked heterotopic bone formation in the medial aspects of the joint, where a new-born ankylotic block occupied most part of the gap created by resecting the coronoid process at the time of the TMJ prosthesis insertion. Conclusions: Despite this adverse event has been sometimes described in the literature, this is the first case in which its occurrence happened several years after the temporomandibular joint replacement. It can be suggested that an accurate assessment of pre-operative risk factors for re-ankylosis (e.g., patients with multiple failed temporomandibular joint surgeries and within-intervention prevention (e.g., strategies to keep the bone interfaces around the implant separated should be better standardized and define in future studies.

Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

2005-01-01

A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7 th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT

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

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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.

Hyperfunctioning thyroid nodules in children.

Science.gov (United States)

Abe, K; Konno, M; Sato, T; Matsuura, N

1980-10-01

We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.

Root nodule structure in Chamaecytisus podolicus

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Monika Skawińska

2017-06-01

Full Text Available By means of microscopic analyses, it was shown that root nodules formed by Chamaecytisus podolicus exhibited all structural features typical for indeterminate nodules of temperate genistean shrubs: (i apical nodule meristem composed of infected and non-infected domains, (ii parenchymatous bacteroid-containing tissue with infected cells only resulting from mitotic activity of infected meristematic cells, (iii absence of infection threads, and (iv convoluted bacteroids singly enclosed in a symbiosome membrane. For the first time, it was shown that the nodule meristem is organized into longitudinal files of sister cells.

Detection of pulmonary nodules

International Nuclear Information System (INIS)

Vanzulli, A.; Zanello, A.; DelMaschio, M.; Paesano, P.; Panizza, P.; DelMaschio, A.

1989-01-01

The authors have prospectively studied 203 pulmonary nodules in 91 patients, selected by CT (gold standard), with both subtraction digital radiography (SDR) and conventional plain film. Subtracted images were obtained by using copper filter inserted between two photostimulable imaging plates. Five radiologists randomly analyzed all conventional and subtracted images. The authors calculated sensitivity, specificity, and positive and negative predictive values for both conventional radiography and SDR. Receiver operating characteristics (ROC) curves were calculated by plotting the number of nodules detected with different degrees of confidence. SDR detected 12% more nodules than conventional radiography. ROC curves demonstrated that the level of confidence was better for SDR (P <.05)

Nodule-Enriched GRETCHEN HAGEN 3 Enzymes Have Distinct Substrate Specificities and Are Important for Proper Soybean Nodule Development

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Suresh Damodaran

2017-11-01

Full Text Available Legume root nodules develop as a result of a symbiotic relationship between the plant and nitrogen-fixing rhizobia bacteria in soil. Auxin activity is detected in different cell types at different stages of nodule development; as well as an enhanced sensitivity to auxin inhibits, which could affect nodule development. While some transport and signaling mechanisms that achieve precise spatiotemporal auxin output are known, the role of auxin metabolism during nodule development is unclear. Using a soybean root lateral organ transcriptome data set, we identified distinct nodule enrichment of three genes encoding auxin-deactivating GRETCHEN HAGEN 3 (GH3 indole-3-acetic acid (IAA amido transferase enzymes: GmGH3-11/12, GmGH3-14 and GmGH3-15. In vitro enzymatic assays showed that each of these GH3 proteins preferred IAA and aspartate as acyl and amino acid substrates, respectively. GmGH3-15 showed a broad substrate preference, especially with different forms of auxin. Promoter:GUS expression analysis indicated that GmGH3-14 acts primarily in the root epidermis and the nodule primordium where as GmGH3-15 might act in the vasculature. Silencing the expression of these GH3 genes in soybean composite plants led to altered nodule numbers, maturity, and size. Our results indicate that these GH3s are needed for proper nodule maturation in soybean, but the precise mechanism by which they regulate nodule development remains to be explained.

[Bone Cell Biology Assessed by Microscopic Approach. Bone histomorphometry of remodeling, modeling and minimodeling].

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Yamamoto, Noriaki; Shimakura, Taketoshi; Takahashi, Hideaki

2015-10-01

Bone histomorphometry is defined as a quantitative evaluation of bone remodeling. In bone remodeling, bone resorption and bone formation are coupled with scalloped cement lines. Another mechanism of bone formation is minimodeling which bone formation and resorption are independent. The finding of minimodeling appeared in special condition with metabolic bone disease or anabolic agents. We need further study for minimodeling feature and mechanism.

Experimental variation of the level and the ratio of angiogenic and osteogenic signaling affects the spatiotemporal expression of bone-specific markers and organization of bone formation in ectopic sites.

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Moser, Norman; Goldstein, Jan; Kauffmann, Phillip; Epple, Matthias; Schliephake, Henning

2018-04-01

The aim of the present study was to test the hypothesis that the ratio of angiogenic and osteogenic signaling affects ectopic bone formation when delivered in different amounts. Porous composite PDLLA/CaCO 3 scaffolds were loaded with rhBMP2 and rhVEGF in different dosage combinations and implanted into the gluteal muscles of 120 adult male Wistar rats. Bone formation and expression of alkaline phosphatase and Runx2 were quantified by histomorphometry. Spatial distribution across the scaffolds was assessed by using a grid that discriminated between the periphery and center of the scaffolds. The evaluation showed that the combined delivery of bone morphogenetic protein BMP2 and VEGF in different dosage combinations did not enhance the overall quantity of ectopic bone formation compared to the delivery of BMP2 alone. The addition of VEGF generally upregulated Runx2 after 4 weeks, which may have retarded terminal osteogenic differentiation. However, slow combined delivery of 1.5-2.0 μg BMP2 combined with 50 ng VEGF165 over a period of 5 weeks supported a more even distribution of bone formation across the implanted scaffolds whereas higher amounts of VEGF did not elicit this effect. The findings suggest that structural organization rather than the quantity of ectopic bone formation is affected by the dosage and the ratio of BMP2 and VEGF levels at the observed intervals. The development of carriers for dual growth factor delivery has to take into account the necessity to carefully balance the ratio of growth release.

In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

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A Roshan-Ghias

2010-02-01

Full Text Available In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid (PLA/ 5% beta-tricalcium phosphate (beta-TCP scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT, all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV: an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds.

Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation

International Nuclear Information System (INIS)

Lee, Jae Hyup; Baek, Hae-Ri; Lee, Ji-Ho; Ryu, Mi Young; Seo, Jun-Hyuk; Lee, Kyung-Mee

2014-01-01

Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (β-TCP) and poloxamer 407-based hydrogel composite and penetration of the β-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524 μm and 464 μm, respectively. We report the in-vivo performance of a composite of β-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with β-TCP/hydrogel composite (containing 5 μg of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of β-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. (paper)

Pulmonary nodule registration in serial CT scans based on rib anatomy and nodule template matching

International Nuclear Information System (INIS)

Shi Jiazheng; Sahiner, Berkman; Chan, H.-P.; Hadjiiski, Lubomir; Zhou, C.; Cascade, Philip N.; Bogot, Naama; Kazerooni, Ella A.; Wu, Y.-T.; Wei, J.

2007-01-01

An automated method is being developed in order to identify corresponding nodules in serial thoracic CT scans for interval change analysis. The method uses the rib centerlines as the reference for initial nodule registration. A spatially adaptive rib segmentation method first locates the regions where the ribs join the spine, which define the starting locations for rib tracking. Each rib is tracked and locally segmented by expectation-maximization. The ribs are automatically labeled, and the centerlines are estimated using skeletonization. For a given nodule in the source scan, the closest three ribs are identified. A three-dimensional (3D) rigid affine transformation guided by simplex optimization aligns the centerlines of each of the three rib pairs in the source and target CT volumes. Automatically defined control points along the centerlines of the three ribs in the source scan and the registered ribs in the target scan are used to guide an initial registration using a second 3D rigid affine transformation. A search volume of interest (VOI) is then located in the target scan. Nodule candidate locations within the search VOI are identified as regions with high Hessian responses. The initial registration is refined by searching for the maximum cross-correlation between the nodule template from the source scan and the candidate locations. The method was evaluated on 48 CT scans from 20 patients. Experienced radiologists identified 101 pairs of corresponding nodules. Three metrics were used for performance evaluation. The first metric was the Euclidean distance between the nodule centers identified by the radiologist and the computer registration, the second metric was a volume overlap measure between the nodule VOIs identified by the radiologist and the computer registration, and the third metric was the hit rate, which measures the fraction of nodules whose centroid computed by the computer registration in the target scan falls within the VOI identified by the

Osteoblastic mesenchymal stem cell sheet combined with Choukroun platelet-rich fibrin induces bone formation at an ectopic site.

Science.gov (United States)

Wang, Zhifa; Weng, Yanming; Lu, Shengjun; Zong, Chunlin; Qiu, Jianyong; Liu, Yanpu; Liu, Bin

2015-08-01

To analyze the effects of platelet-rich fibrin (PRF) on mesenchymal stem cells (MSCs) in vitro and investigate in vivo bone formation by MSC sheets with PRF. Cell proliferation and expression of osteogenesis-related genes within MSC sheets were assessed upon exposure to PRF from the same donors. We then injected MSC sheet fragments with or without PRF subcutaneously in nude mice and assessed bone formation by micro-computed tomography and histological analyses. PRF significantly stimulated MSC proliferation and osteogenesis in vitro. MSC sheets injected with or without PRF formed new bone, but those with PRF produced significantly more and denser bone. MSC sheets can be used to generate tissue engineered bone upon injection, and PRF increases the osteogenic capacity of MSC sheets in vitro and in vivo. © 2014 Wiley Periodicals, Inc.

Diffusion-weighted MR imaging of thyroid nodules

International Nuclear Information System (INIS)

Bozgeyik, Zulkif; Coskun, Sonay; Ogur, Erkin; Dagli, A.F.; Ozkan, Yusuf; Sahpaz, Fatih

2009-01-01

The purpose of our study was to determine the diagnostic role of diffusion-weighted imaging (DWI) in the differentiating of malignant and benign thyroid nodules by using fine needle aspiration biopsy cytology criteria as a reference standard. The apparent diffusion coefficient (ADC) values of the normal-looking thyroid parenchyma were also evaluated both in normal patients and in patients with nodules. Between March 2007 and February 2008, 76 consecutive patients with ultrasound-diagnosed thyroid nodules and 20 healthy subjects underwent diffusion-weighted MR imaging by using single-shot spin echo, echo planar imaging. A total of 93 nodules were included in the study using the following b factors 100, 200, and 300 mm 2 /s. ADC values of thyroid nodules and normal area in all subjects were calculated and compared using suitable statistical analysis. Mean ADC values for malignant and benign nodules were 0.96±0.65 x 10 -3 and 3.06±0.71 x 10 -3 mm 2 /s. for b-300 factor, 0.56±0.43 x 10 -3 and 1.80±0.60 x 10 -3 mm 2 /s for b-200, and 0.30±0.20 x 10 -3 and 1.15±0.43 x 10 -3 mm 2 /s, for b-300, respectively. Mean ADC values of malignant nodules were lower than benign nodules. There were significant differences in ADC values between benign and malignant nodules. ADC values among normal-appearing thyroid parenchyma of patients and normal-appearing thyroid parenchyma of healthy subjects were insignificant at all b factors. Benign nodules have higher ADC values than malignant ones. DWI may be helpful in differentiating malign and benign thyroid nodules. (orig.)

A Bile Duct Stone Formation around a Fish Bone as a Nidus after Pancreatoduodenectomy

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Tomoki Sakakida

2018-02-01

Full Text Available We report a rare case of bile duct stone formation around an ingested fish bone as a nidus after pancreatoduodenectomy. A 78-year-old woman was admitted to our department for fever and epigastric pain. Abdominal computed tomography revealed an elongated bile duct stone containing a linearly shaped foreign body of bone density. Enteroscopic lithotomy was performed using single balloon enteroscopy to safely remove the stone and foreign body from the bile duct. The foreign body was determined to be a fish bone by pathological examination and component analysis.

Management of thyroid nodules in children and adolescents

NARCIS (Netherlands)

Wiersinga, Wilmar M.

2007-01-01

Thyroid nodules in childhood and adolescence are less prevalent but more often malignant than in adulthood. Malignant nodules are predominantly papillary cancers; benign nodules are mostly solid colloid nodules/adenomas, but can be cystic or due lymphocytic thyroiditis. Previous neck irradiation

Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

International Nuclear Information System (INIS)

Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

1982-01-01

Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

US Diagnosis for Thyroid Nodules with an Indeterminate Cytology

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Ha, Jong Geun; Kim, Dong Wook [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Kang, Tae Woo [Saegyaero Hospital, Busan (Korea, Republic of)

2011-09-15

We wanted to assess the diagnostic efficacy of thyroid ultrasound (US) for evaluating thyroid nodules with indeterminate cytology. Among 1865 nodules in 1278 patients who received a prospective US diagnosis of their thyroid nodule(s) and who subsequently underwent US-guided fine-needle aspiration, 130 nodules with indeterminate cytology were enrolled in the study. Each thyroid nodule was prospectively classified by a single radiologist into 1 of 5 diagnostic categories: 'benign', 'probably benign', 'indeterminate', 'suspicious for malignancy' and 'malignant.' The solid nodules were classified using all 5 categories and the partially cystic nodules classified using 4 categories ('indeterminate' was omitted). We calculated the diagnostic efficacy of thyroid US by comparing the US diagnoses with the pathology results. Of 130 nodules with indeterminate cytology (130/1865, 7.0%), 62 nodules were surgically removed. Nineteen nodules were assigned to the indeterminate category on US. The malignantly rate of the US-indeterminate category was 56.5% (35/62). The sensitivity, specificity and positive and negative predictive values were 81.0%, 81.8%, 81.0%, 81.8% and 81.4%, respectively, when US-indeterminate nodules were excluded. There was no significant difference of diagnostic efficacy when these nodules were reclassified as malignant, but there was a significant difference of diagnostic efficacy when these nodules were reclassified as benign. Our US classification may be a feasible method for managing thyroid nodules with indeterminate cytology

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.

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

Overexpression of BMP3 in the developing skeleton alters endochondral bone formation resulting in spontaneous rib fractures.

Science.gov (United States)

Gamer, Laura W; Cox, Karen; Carlo, Joelle M; Rosen, Vicki

2009-09-01

Bone morphogenetic protein-3 (BMP) has been identified as a negative regulator in the skeleton as mice lacking BMP3 have increased bone mass. To further understand how BMP3 mediates bone formation, we created transgenic mice overexpressing BMP3 using the type I collagen promoter. BMP3 transgenic mice displayed spontaneous rib fractures that were first detected at E17.0. The fractures were due to defects in differentiation of the periosteum and late hypertrophic chondrocytes resulting in thinner cortical bone with decreased mineralization. As BMP3 modulates BMP and activin signaling through ActRIIB, we examined the ribs of ActRIIB receptor knockout mice and found they had defects in late chondrogenesis and mineralization similar to BMP3 transgenic mice. These data suggest that BMP3 exerts its effects in the skeleton by altering signaling through ActRIIB in chondrocytes and the periosteum, and this results in defects in bone collar formation and late hypertrophic chondrocyte maturation leading to decreased mineralization and less bone. 2009 Wiley-Liss, Inc.

Persistent pulmonary subsolid nodules: model-based iterative reconstruction for nodule classification and measurement variability on low-dose CT

International Nuclear Information System (INIS)

Kim, Hyungjin; Kim, Seong Ho; Lee, Sang Min; Lee, Kyung Hee; Park, Chang Min; Park, Sang Joon; Goo, Jin Mo

2014-01-01

To compare the pulmonary subsolid nodule (SSN) classification agreement and measurement variability between filtered back projection (FBP) and model-based iterative reconstruction (MBIR). Low-dose CTs were reconstructed using FBP and MBIR for 47 patients with 47 SSNs. Two readers independently classified SSNs into pure or part-solid ground-glass nodules, and measured the size of the whole nodule and solid portion twice on both reconstruction algorithms. Nodule classification agreement was analyzed using Cohen's kappa and compared between reconstruction algorithms using McNemar's test. Measurement variability was investigated using Bland-Altman analysis and compared with the paired t-test. Cohen's kappa for inter-reader SSN classification agreement was 0.541-0.662 on FBP and 0.778-0.866 on MBIR. Between the two readers, nodule classification was consistent in 79.8 % (75/94) with FBP and 91.5 % (86/94) with MBIR (p = 0.027). Inter-reader measurement variability range was -5.0-2.1 mm on FBP and -3.3-1.8 mm on MBIR for whole nodule size, and was -6.5-0.9 mm on FBP and -5.5-1.5 mm on MBIR for solid portion size. Inter-reader measurement differences were significantly smaller on MBIR (p = 0.027, whole nodule; p = 0.011, solid portion). MBIR significantly improved SSN classification agreement and reduced measurement variability of both whole nodules and solid portions between readers. (orig.)

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease].

Science.gov (United States)

Fekih, Monia; Sahli, Hela; Ben Mustapha, Nadia; Mestiri, Imen; Fekih, Moncef; Boubaker, Jalel; Kaabachi, Naziha; Sellami, Mohamed; Kallel, Lamia; Filali, Azza

2013-01-01

Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

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

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Christine Knabe

2017-07-01

Full Text Available 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 bone area and biomaterial area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 months later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller biomaterial area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the HyAc hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting. The greater bone formation observed with TCP-P may be related to the difference in grain size of the TCP granules and/or the addition of the HyAc.

A role for PERK in the mechanism underlying fluoride-induced bone turnover

International Nuclear Information System (INIS)

Sun, Fei; Li, Xining; Yang, Chen; Lv, Peng; Li, Guangsheng; Xu, Hui

2014-01-01

While it has been well-documented that excessive fluoride exposure caused the skeletal disease and osteoblasts played a critical role in the advanced skeletal fluorosis, the underlying mechanism that mediated these effects remain poorly understood. The present study was undertaken to examine the effect of fluoride on bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features of high bone turnover in fluoride-treated rats, which was supported by an increase of osteogenic and osteoclastogenic genes expression in different stages of fluoride exposure. The skeletal toxicity of fluoride was accompanied by activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). A novel finding of this study was that expression of PKR-like endoplasmic reticulum kinase (PERK) was the same trend with receptor activator for nuclear factor-κ B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2) was the same trend with Runt-related transcription factor 2 (Runx2) in bones of rats exposed to varied fluoride condition. Based on these data, we hypothesized that up-regulation of PERK probably played a role in mediating bone turnover induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was demonstrated through analysis of alkaline phosphatase (ALP) activity and mineralized nodules formation. Meantime, an increase of binding immunoglobulin protein (BiP) expression indicated the active ER stress in cells exposed to various dose of fluoride. Blocking PERK expression using siRNA showed the obvious decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells exposed to certain dose of fluoride that could positively stimulate osteoblastic viability. In conclusion these findings underscore the importance of PERK in modulating fluoride induced bone formation and bone resorption. Understanding the link between PERK and bone turnover could probe into the mechanism underlying different bone lesion of

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

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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.

Nitrogen assimilation in soybean nodules, 1

International Nuclear Information System (INIS)

Ohyama, Takuji; Kumazawa, Kikuo

1980-01-01

In order to elucidate the pathways to assimilate the ammonia produced by N 2 -fixation in soybean nodules, 15 N-labeled compounds were administered to intact nodules or nodule slices pretreated with various inhibitors of nitrogen assimilation. After exposure to 15 N 2 , 15 N-incorporation into various nitrogenous compounds was investigated in attached nodules injected with methionine sulfoximine (MSX) or azaserine (AS). MSX treatment increased the 15 N content of ammonia more than 6 times, however, depressed 15 N content of most of amides and amino acids. AS treatment enhanced 15 N content of amido-N of glutamine as well as ammonia, but decreased amino-N of glutamine and most of amino acids. Experiments with nodule slices pretreated with MSX or AS solution and then fed with 15 N-labeled ammonia or amido- 15 N of glutamine showed the same trends. Aminooxyacetate inhibited nitrogen flow from glutamic acid to other amino acids. These results strongly indicate that the ammonia produced by N 2 -fixation is assimilated by GS/GOGAT system to glutamic acid and then transaminated to various amino acids in situ. 15 N-incorporation patterns in nodule slices fed with 15 N-labeled ammonia, hydroxylamine, nitrite were similar, but nitrate seemed to be reduced in a definite compartment and assimilated similarly as in intact nodules fed with 15 N 2 (author)

Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.

Science.gov (United States)

Wang, Xiuli; Cui, Fuai; Madhu, Vedavathi; Dighe, Abhijit S; Balian, Gary; Cui, Quanjun

2011-02-01

A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes. The cells expressing both genes elevated mRNA expression of RunX2 and β-catenin and alkaline phosphatase activity compared to cells from other groups. In vivo, X-ray and micro-CT analysis of the retrieved implants revealed more ectopic bone formation at 2 and 3 weeks but not at 4 weeks compared to other groups. The results indicate that the combination of the therapeutic growth factors potentiates cell differentiation and may promote osteogenesis.

Activated protein C (APC) can increase bone anabolism via a protease-activated receptor (PAR)1/2 dependent mechanism.

Science.gov (United States)

Shen, Kaitlin; Murphy, Ciara M; Chan, Ben; Kolind, Mille; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Xue, Meilang; Park, Sang-Youel; Little, David G; Jackson, Chris J; Schindeler, Aaron

2014-12-01

Activated Protein C (APC) is an anticoagulant with strong cytoprotective properties that has been shown to promote wound healing. In this study APC was investigated for its potential orthopedic application using a Bone Morphogenetic Protein 2 (rhBMP-2) induced ectopic bone formation model. Local co-administration of 10 µg rhBMP-2 with 10 µg or 25 µg APC increased bone volume at 3 weeks by 32% (N.S.) and 74% (pAPC are largely mediated by its receptors endothelial protein C receptor (EPCR) and protease-activated receptors (PARs). Cultured pre-osteoblasts and bone nodule tissue sections were shown to express PAR1/2 and EPCR. When pre-osteoblasts were treated with APC, cell viability and phosphorylation of ERK1/2, Akt, and p38 were increased. Inhibition with PAR1 and sometimes PAR2 antagonists, but not with EPCR blocking antibodies, ameliorated the effects of APC on cell viability and kinase phosphorylation. These data indicate that APC can affect osteoblast viability and signaling, and may have in vivo applications with rhBMP-2 for bone repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Osteoblast Differentiation and Bone Formation Gene Expression in Strontium-inducing Bone Marrow Mesenchymal Stem Cell

OpenAIRE

SILA-ASNA, MONNIPHA; BUNYARATVEJ, AHNOND; Maeda, Sakan; Kitaguchi, Hiromichi; BUNYARATAVEJ, NARONG

2007-01-01

Osteoblastic differentiation from human mesenchymal stem cell (hMSCs) is animportant step of bone formation. We studied the in vitro induction of hMSCs byusing strontium ranelate, a natural trace amount in water, food and human skeleton.The mRNA synthesis of various osteoblast specific genes was assessed by means ofreverse transcription polymerase chain reaction (RT-PCR). In the hMSCs culture,strontium ranelate could enhance the induction of hMSCs to differentiate intoosteoblasts. Cbfa1 gene ...

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

Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

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Mary C. Farach-Carson

2017-08-01

Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

Composition, characteristics and genesis of the ferromanganese crusts and nodules from the Indian and Pacific oceans

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Chen, S.; Peng, X.

2017-12-01

Ferromanganese crusts and nodules are considered to be one of the most important players in the geochemical cycling of the oceans. However, the lack of integrated studies affects our explicit understanding of the mineralization, characteristics and genesis of the crusts and nodules. In this study, the mineralogy, geochemistry and molecular biology in ferromanganese crusts and nodules obtained from various oceans were explored. The crusts/nodules are composed predominantly of vernadite (δ-MnO2) and amorphous Fe oxides/hydroxides. The shale normalized negative Ce-anomalies, characteristic of hydrothermal oxides, are retained in JL and TVG6. In hydrogenous oxides, the positive Ce-anomalies were found in 21V-S7 and DY119-4. The iron isotopic compositions range between -0.543 and -0.002‰ in δ56Fe IRMM14. Using molecular 16S rRNA gene techniques (clone libraries, real-time PCR) we show that nodules (JL-B and TVG6) provide a suitable habitat for prokaryotes with an abundant and diverse prokaryotic community dominated by Mn(II)-oxidizing bacteria (Pseudomonas putida GB-1). These bacteria were not detected in the crust samples (21V-S7 and DY119-4). The results suggest that a biologically driven Manganese cycle inside the nodule that may be relevant to their formation.

Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women

International Nuclear Information System (INIS)

Thomsen, K.; Riis, B.; Christiansen, C.

1986-01-01

The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of /sup 99m/technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

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Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

Can Spatiotemporal Fluoride (18F-) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET/CT.

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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 ( 18 F - ) 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, 18 F - 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 18 F - 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 18 F - 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 Frame TM (TSF) by comparing clinical healing progress with spatiotemporal fluoride ( 18 F - ) 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

Free Radicals Formation of Irradiated Lyophilized Can-Cellous Human and Bovine Bone

International Nuclear Information System (INIS)

Abbas, Basril; Sudiro, Sutjipto; Hilmy, Nazly

2000-01-01

Radiation sterilization of lyophilized human and bovine bone as allograft and xenograft have been produced and used in orthopaedic practice in Indonesia routinely. It is well known from radio biologic studies that one of the most pronounce effects of ionizing radiation on biologic species produced the free radicals that influence the physico-chemical as well as the mechanical properties of irradiated bone. The aim of our study is to investigate the free radicals formation of irradiated lyophilized cancellous triple A bone (Autolyzed Antigen-Extracted Allograft) produced by Batan Research Tissue Bank in Jakarta. The cancellous triple A were prepared according to AATB (American Association of Tissue Bank) method. Gamma Irradiations was done at doses of 10, 20 and 30 kGy with a dose rate of 7,5 kGy/h at room temperature (30 o C± 2 o C). Measurements of free radicals was done at 24 o C ±1 o C within 30 minutes after irradiational and measurement were continued up to 9 months of storage using a JES-REIX ESR Spectrophotometer (JEOL) with Mn exp. ++ standard. Parameters measured, were the effects of mechanical grinding, water immersion and irradiation dose on free radicals formation in the bone. Results show that the signal area of ESR spectra from irradiated bovine bone of 30 kGy was higher than those of human bone I.e. 1,4 x 10 exp. 7 dan 6,4 x 10 exp. 6 Au (arbitrary unit)/g samples respectively. The signal of ESR spectra increased linearly with increasing dose in the range of 10-30 kGy and it will reduce about 30% caused by water immersion. The ESR signal reduced sharply after 2 days and gradually decreased up to 14 days and then became constant up to 9 months of storage at room temperature. A certain method of crushing can produce free radicals. Key Words: free radical, irradiation, allograft, xenograft, mechanical-grinding

Persistent pulmonary subsolid nodules: model-based iterative reconstruction for nodule classification and measurement variability on low-dose CT.

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Kim, Hyungjin; Park, Chang Min; Kim, Seong Ho; Lee, Sang Min; Park, Sang Joon; Lee, Kyung Hee; Goo, Jin Mo

2014-11-01

To compare the pulmonary subsolid nodule (SSN) classification agreement and measurement variability between filtered back projection (FBP) and model-based iterative reconstruction (MBIR). Low-dose CTs were reconstructed using FBP and MBIR for 47 patients with 47 SSNs. Two readers independently classified SSNs into pure or part-solid ground-glass nodules, and measured the size of the whole nodule and solid portion twice on both reconstruction algorithms. Nodule classification agreement was analyzed using Cohen's kappa and compared between reconstruction algorithms using McNemar's test. Measurement variability was investigated using Bland-Altman analysis and compared with the paired t-test. Cohen's kappa for inter-reader SSN classification agreement was 0.541-0.662 on FBP and 0.778-0.866 on MBIR. Between the two readers, nodule classification was consistent in 79.8 % (75/94) with FBP and 91.5 % (86/94) with MBIR (p = 0.027). Inter-reader measurement variability range was -5.0-2.1 mm on FBP and -3.3-1.8 mm on MBIR for whole nodule size, and was -6.5-0.9 mm on FBP and -5.5-1.5 mm on MBIR for solid portion size. Inter-reader measurement differences were significantly smaller on MBIR (p = 0.027, whole nodule; p = 0.011, solid portion). MBIR significantly improved SSN classification agreement and reduced measurement variability of both whole nodules and solid portions between readers. • Low-dose CT using MBIR algorithm improves reproducibility in the classification of SSNs. • MBIR would enable more confident clinical planning according to the SSN type. • Reduced measurement variability on MBIR allows earlier detection of potentially malignant nodules.

Subsolid pulmonary nodules: imaging evaluation and strategic management.

Science.gov (United States)

Godoy, Myrna C B; Sabloff, Bradley; Naidich, David P

2012-07-01

Given the higher rate of malignancy of subsolid pulmonary nodules and the considerably lower growth rate of ground-glass nodules (GGNs), dedicated standardized guidelines for management of these nodules have been proposed, including long-term low-dose computed tomography (CT) follow-up (≥3 years). Physicians must be familiar with the strategic management of subsolid pulmonary nodules, and should be able to identify imaging features that suggest invasive adenocarcinoma requiring a more aggressive management. Low-dose CT screening studies for early detection of lung cancer have increased our knowledge of pulmonary nodules, and in particular our understanding of the strong although imperfect correlation of the subsolid pulmonary nodules, including pure GGNs and part-solid nodules, with the spectrum of preinvasive to invasive lung adenocarcinoma. Serial CT imaging has shown stepwise progression in a subset of these nodules, characterized by increase in size and density of pure GGNs and development of a solid component, the latter usually indicating invasive adenocarcinoma. There is close correlation between the CT features of subsolid nodules (SSNs) and the spectrum of lung adenocarcinoma. Standardized guidelines are suggested for management of SSNs.

Improved pulmonary nodule classification utilizing quantitative lung parenchyma features.

Science.gov (United States)

Dilger, Samantha K N; Uthoff, Johanna; Judisch, Alexandra; Hammond, Emily; Mott, Sarah L; Smith, Brian J; Newell, John D; Hoffman, Eric A; Sieren, Jessica C

2015-10-01

Current computer-aided diagnosis (CAD) models for determining pulmonary nodule malignancy characterize nodule shape, density, and border in computed tomography (CT) data. Analyzing the lung parenchyma surrounding the nodule has been minimally explored. We hypothesize that improved nodule classification is achievable by including features quantified from the surrounding lung tissue. To explore this hypothesis, we have developed expanded quantitative CT feature extraction techniques, including volumetric Laws texture energy measures for the parenchyma and nodule, border descriptors using ray-casting and rubber-band straightening, histogram features characterizing densities, and global lung measurements. Using stepwise forward selection and leave-one-case-out cross-validation, a neural network was used for classification. When applied to 50 nodules (22 malignant and 28 benign) from high-resolution CT scans, 52 features (8 nodule, 39 parenchymal, and 5 global) were statistically significant. Nodule-only features yielded an area under the ROC curve of 0.918 (including nodule size) and 0.872 (excluding nodule size). Performance was improved through inclusion of parenchymal (0.938) and global features (0.932). These results show a trend toward increased performance when the parenchyma is included, coupled with the large number of significant parenchymal features that support our hypothesis: the pulmonary parenchyma is influenced differentially by malignant versus benign nodules, assisting CAD-based nodule characterizations.

Impaired bone formation in Pdia3 deficient mice.

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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.

Computer-aided Detection Fidelity of Pulmonary Nodules in Chest Radiograph

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Nikolaos Dellios

2017-01-01

Full Text Available Aim: The most ubiquitous chest diagnostic method is the chest radiograph. A common radiographic finding, quite often incidental, is the nodular pulmonary lesion. The detection of small lesions out of complex parenchymal structure is a daily clinical challenge. In this study, we investigate the efficacy of the computer-aided detection (CAD software package SoftView™ 2.4A for bone suppression and OnGuard™ 5.2 (Riverain Technologies, Miamisburg, OH, USA for automated detection of pulmonary nodules in chest radiographs. Subjects and Methods: We retrospectively evaluated a dataset of 100 posteroanterior chest radiographs with pulmonary nodular lesions ranging from 5 to 85 mm. All nodules were confirmed with a consecutive computed tomography scan and histologically classified as 75% malignant. The number of detected lesions by observation in unprocessed images was compared to the number and dignity of CAD-detected lesions in bone-suppressed images (BSIs. Results: SoftView™ BSI does not affect the objective lesion-to-background contrast. OnGuard™ has a stand-alone sensitivity of 62% and specificity of 58% for nodular lesion detection in chest radiographs. The false positive rate is 0.88/image and the false negative (FN rate is 0.35/image. From the true positive lesions, 20% were proven benign and 80% were malignant. FN lesions were 47% benign and 53% malignant. Conclusion: We conclude that CAD does not qualify for a stand-alone standard of diagnosis. The use of CAD accompanied with a critical radiological assessment of the software suggested pattern appears more realistic. Accordingly, it is essential to focus on studies assessing the quality-time-cost profile of real-time (as opposed to retrospective CAD implementation in clinical diagnostics.

Possible role of glutamine synthetase in the NO signaling response in root nodules by contributing to the antioxidant defenses

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Liliana Santos Silva

2013-09-01

Full Text Available Nitric oxide (NO is emerging as an important regulatory player in the Rhizobium-legume symbiosis. The occurrence of NO during several steps of the symbiotic interaction suggests an important, but yet unknown, signaling role of this molecule for root nodule formation and functioning. The identification of the molecular targets of NO is key for the assembly of the signal transduction cascade that will ultimately help to unravel NO function. We have recently shown that the key nitrogen assimilatory enzyme Glutamine Synthetase (GS is a molecular target of NO in root nodules of Medicago truncatula, being post-translationally regulated by tyrosine nitration in relation to nitrogen fixation. In functional nodules of M. truncatula NO formation has been located in the bacteroid containing cells of the fixation zone, where the ammonium generated by bacterial nitrogenase is released to the plant cytosol and assimilated into the organic pools by plant GS. We propose that the NO-mediated GS post-translational inactivation is connected to nitrogenase inhibition induced by NO and is related to metabolite channeling to boost the nodule antioxidant defenses. Glutamate, a substrate for GS activity is also the precursor for the synthesis of glutathione (GSH, which is highly abundant in root nodules of several plant species and known to play a major role in the antioxidant defense participating in the ascorbate/GSH cycle. Existing evidence suggests that upon NO-mediated GS inhibition, glutamate could be channeled for the synthesis of GSH. According to this hypothesis, GS would be involved in the NO-signaling responses in root nodules and the NO-signaling events would meet the nodule metabolic pathways to provide an adaptive response to the inhibition of symbiotic nitrogen fixation by reactive nitrogen species (RNS.

Partially Cystic Thyroid Nodules: Ultrasound Findings of Malignancy

Energy Technology Data Exchange (ETDEWEB)

Park, Jang Mi; Choi, Yoon Jung; Kwag, Hyon Joo [Dept. of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2012-09-15

To seek for the ultrasound (US) findings of partially cystic thyroid nodules that are associated with malignancy. We reviewed the US characteristics of 22 surgically confirmed partially cystic papillary carcinomas, and compared them with those of 80 benign partially cystic nodules. The review cases were selected in a random order from a total of 1029 partially cystic nodules that were diagnosed with an US-guided fine needle aspiration biopsy over a period of 8 years (June 2003 to October 2010) at our institution. In partially cystic thyroid nodules, a taller-than-wide shape (100%, p<0.001) and spiculated or microlobulated margin (58.3%, p 0.003) were significantly associated with malignancy. In terms of internal solid portion of the nodule, eccentric configuration (68.0%, p<0.001), non-smooth margin (81.3%, p<0.001), hypoechogenecity (30.0%, p<0.042), and microcalcification (89.5%, p<0.001) were more frequently demonstrated in malignant nodules than benign ones. In partially cystic thyroid nodules, understanding the characteristics of US findings is important to make a precise diagnosis of malignant nodules.

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

NTRODUCTION: Animal studies indicate that n-3 long-chain polyunsaturated fatty acids (LCPUFAs) increase bone formation. To our knowledge, no studies have examined this in growing humans. This study investigated whether bone mass and markers of bone formation and growth were (i) associated...... 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...

Significance of size in occurrence, distribution, morphological characteristics, abundance, and resource evaluation of polymetallic nodules

Digital Repository Service at National Institute of Oceanography (India)

Valsangkar, A.B.; Rebello, J.M.S.

p i bi (8) R f el p bi (5) R p bi (3) - b bl p bi (4) R b bl bi (4) - - ( ): Total number of nodule types present Texture: r-rough, g- gritty, s- smooth Shape: R- rounded, ep-ellipsoidal/ elliptical, ds-discoidal, b- botryoidal, bl...; Valsngkar and Karisiddaiah 1993; Vineesh et al. 2009; Mukhopadhyay and Gosh 2010). It therefore appears that not only one but combination of all these parameters are responsible for the formation of the CIB nodules. The main objective of the present study...

Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute - in vivo animal study.

Science.gov (United States)

Dau, Michael; Kämmerer, Peer W; Henkel, Kai-Olaf; Gerber, Thomas; Frerich, Bernhard; Gundlach, Karsten K H

2016-05-01

Healing characteristics as well as level of tissue integration and degradation of two different nanostructured hydroxyapatite bone substitute materials (BSM) in comparison with a deproteinized hydroxyapatite bovine BSM were evaluated in an in vivo animal experiment. In the posterior mandible of 18 minipigs, bilateral mono cortical critical size bone defects were created. Randomized augmentation procedures with NanoBone(®) (NHA1), Ostim(®) (NHA2) or Bio-Oss(®) (DBBM) were conducted (each material n = 12). Samples were analyzed after five (each material n = 6) and 8 months (each material n = 6). Defect healing, formation of soft tissue and bone as well as the amount of remaining respective BSM were quantified both macro- and microscopically. For NHA2, the residual bone defect after 5 weeks was significantly less compared to NHA1 or DBBM. There was no difference in residual BSM between NHA1 and DBBM, but the amount in NHA2 was significantly lower. NHA2 also showed the least amount of soft tissue and the highest amount of new bone after 5 weeks. Eight months after implantation, no significant differences in the amount of residual bone defects, in soft tissue or in bone formation were detected between the groups. Again, NHA2 showed significant less residual material than NHA1 and DBBM. We observed non-significant differences in the biological hard tissue response of NHA1 and DBBM. The water-soluble NHA2 initially induced an increased amount of new bone but was highly compressed which may have a negative effect in less stable augmentations of the jaw. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Current status of fine needle aspiration for thyroid nodules.

Science.gov (United States)

Ogilvie, Jennifer B; Piatigorsky, Eli J; Clark, Orlo H

2006-01-01

When not to perform fine needle aspiration of a thyroid nodule In summary, FNA of thyroid nodules has become one of the most useful, safe, and accurate tools in the diagnosis of thyroid pathology. Thyroid nodules that should be considered for FNA include any firm, palpable, solitary nodule or nodule associated with worrisome clinical features (rapid growth, attachment to adjacent tissues, new hoarseness, or palpable lymphadenopathy). FNA should also be performed on nodules with suspicious ultrasonographic features (microcalcifications, rounded shape, predominantly solid composition); dominant or atypical nodules in multinodular goiter; complex or recurrent cystic nodules; or any nodule associated with palpable or ultrasonographically abnormal cervical lymph nodes. Finally, FNA should be performed on any abnormal-appearing or palpable cervical lymph nodes. The management of thyroid nodules based on FNA findings is summarized in Table 2. It can be argued that in certain circumstances the results of thyroid FNA do not change the surgical management of a thyroid nodule, and thus preoperative FNA may be unnecessary. These cases include solitary nodules in patients who have a strong family history of thyroid cancer, multiple endocrine neoplasia type II, or radiation to the head and neck. These patients when they have thyroid nodules have at least a 40% risk for thyroid cancer and frequent multifocal or bilateral disease and should undergo total thyroidectomy with or without central neck lymph node dissection. Patients who have multinodular goiter and compressive symptoms, patients who have Graves disease and a thyroid nodule, or patients who have large (greater than 4 cm) or symptomatic unilateral thyroid nodules could also be considered for total thyroidectomy or lobectomy as indicated without preoperative FNA. Finally, patients who have a solitary hyperfunctioning nodule on radioiodine scan and a suppressed TSH have an extremely low incidence of malignancy and may be

Ultrasound stratification of the FDG-avid thyroid nodule

International Nuclear Information System (INIS)

Beech, P.; Lavender, I.; Jong, I.; Soo, G.; Ramdave, S.; Chong, A.; Nandurkar, D.

2016-01-01

Aim: To determine whether the malignancy risk in an 2-["1"8F]-fluoro-2-deoxy-D-glucose (FDG)-avid thyroid nodule can be stratified according to the presence or absence of suspicious ultrasound features and thereby identify which nodules require further cytological assessment. Materials and methods: A retrospective review of FDG-positron-emission tomography (PET) combined with computed tomography (CT) studies with FDG-avid thyroid nodules (defined as FDG uptake greater than blood pool) that were further assessed with ultrasound and fine-needle aspiration cytology or surgery was performed. FDG-avid thyroid nodules were classified as having either suspicious ultrasound features (marked hypo-echogenicity, irregular margins, microcalcifications, marked hypervascularity, or nodules that were taller than they were wide) or no suspicious ultrasound features and these findings were correlated with the subsequent cytological results. Results: Forty-eight FDG-avid thyroid nodules were assessed. On cytological assessment five nodules were malignant (10.4%), nine were indeterminate (18.75%), and 34 were benign (70.8%). On ultrasound, 24 (50%) had no suspicious features and 24 (50%) had one or more suspicious features. Of the nodules with no suspicious features, 22 (91.6%) were benign, two (8.3%) were indeterminate, and none were malignant. Of the nodules with suspicious features, five (20.8%) were malignant, seven (29.1%) were indeterminate, and 12 (50%) were benign. The absence of suspicious ultrasound features demonstrated a strong association with benign cytology (p=0.009). Out of the suspicious sonographic features, marked hypoechoic appearance (p=0.02), irregular margins (p=0.009), and taller than wide morphology (p=0.04) were statistically most significantly associated with malignancy. Conclusion: The rate of malignancy in FDG-avid thyroid nodules is low in the absence of specific suspicious ultrasound features. The SUV values are non-discriminatory to differentiate

Delayed Surgery for Parathyroid Adenoma Misdiagnosed as a Thyroid Nodule and Treated with Radiofrequency Ablation

Directory of Open Access Journals (Sweden)

Ho-Su Kim

2013-09-01

Full Text Available Primary hyperparathyroidism occurs as a result of isolated parathyroid adenoma in 80% to 85% of all cases. A 99mtechnetium (99mTc sestamibi scan or neck ultrasonography is used to localize the neoplasm prior to surgical intervention. A 53-year-old female was referred for the exclusion of metabolic bone disease. She presented with low back pain that had persisted for the past 6 months and elevated serum alkaline phosphatase (1,253 IU/L. Four years previously, she had been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was determined to be pathologically benign. Radiofrequency ablation was performed at the same hospital because the nodule was still growing during the follow-up period 2 years before the visit to our hospital, and the procedure was unsuccessful in reducing the size of the nodule. The results of the laboratory tests in our hospital were as follows: serum calcium, 14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH, 1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patient's thyroid; left parathyroidectomy was performed. This case indicated that thyroid ultrasonographers and pathologists need to be experienced enough to differentiate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm.

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

Science.gov (United States)

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

2017-01-01

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 (re)modeling, 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 (re)modeling 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.

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.

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

) 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...

Ultrasound-Guided Fine-Needle Aspiration Biopsy of Multiple Thyroid Nodules

International Nuclear Information System (INIS)

Kim, Ji Dae; Bae, Il Hun; Lee, Seung Young; Han, Gi Seok; Cha, Sang Hun; Kim, Sung Jin; Park, Kil Sun; Koong, Sung Soo; Lee, Ok Jun

2006-01-01

To standardize the number of nodules which necessitates ultrasound-guided, fine-needle, aspiration biopsy in patients who have multiple thyroid nodules with the same sonographic characteristics as each other. From February, 2002 to March, 2004, among patients whose diagnosis was confirmed by ultrasound-guided, fine-needle, aspiration biopsy, 545 nodules of 203 patients were found in sonography with more than two thyroid nodules. Each thyroid gland nodule was classified on a score from 0 to 2 points on the basis of the following 5 characteristics: internal content, margin, echogenicity, shape and calcification in sonography. When the score of all characteristics was the same, by deciding on nodules with the same sonographic characteristics and with the score of at least one characteristic being different, we divided the nodules with different sonographic characteristics in a patient. By methods such as given in the preceding descriptions, patients with multiple thyroid nodules were separated into two groups: one in which all nodules had the same sonographic characteristics and another in which nodules have at least one different sonographic characteristic. Then, each pathologic result was searched for the same case and different case in each patient group. Among the 203 patients who were diagnosed with multiple thyroid nodules in ultrasonography, 79 patients (38.9%) had nodules with the same ultrasonographic characteristics and 124 patients (61.1%) had nodules with at least one different ultrasonographic characteristic. All 79 patient's nodules with the same ultrasonographic characteristics in each patient showed the same pathologic result in all cases (100.0%) and there was no case showing a different pathologic result. Otherwise, among the 124 patient's nodules with different ultrasonographic characteristics, each patient showed the same pathologic result in 111 (89.5%) and different pathologic result in 13 (10.5%). In patients who have multiple thyroid nodules

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.

Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus

International Nuclear Information System (INIS)

Kearns, M.; Lala, P.K.

1982-01-01

Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells

Evaluation for dinitrogen fixation of induced wheat nodules by 15N isotope dilution method

International Nuclear Information System (INIS)

Yao Yunyin; Zhen Ming; Chang Xizhong

1993-11-01

The results in pot experiments showed that the treating of 2,4-D and Azorhizobium caulinodans (2,4-D+A) could induce para-nodule formation on wheat roots. Plants treated grew normally. The plant height and dry weight are significantly higher than reference plants which are treated with 2,4-D+azorhizobium sterilized (2,4-D+AS). The nitrogenase activity is detected by ARA method. The N yield of most treated plants, especially in root systems, is higher than reference group that is measured by Kjeldahl method. The atom % 15 N excess in leaf and stem of treated plants measured by 15 N isotope dilution method is lower than that of reference group. Through four years experiments, it shows that para-nodules of wheat treated with 2,4-D+A could fix N 2 from air, but the ability of nitrogen fixation is lower and unstable. Although the nodulation efficiency could reach 100%, not each para-nodule induced can present activity of dinitrogen fixation. The amount of N fixed is 0.05∼18.1 mg/pot (0.01∼3.87 mg/plant). The net %Ndfa is 2.32%∼18.07%. The free-living N 2 fixing activity of azorhizobium is detected by 15 N isotope dilution method. The calculation of %Ndfa of nodulated wheat accurately is also discussed

Host range, symbiotic effectiveness and nodulation competitiveness ...

African Journals Online (AJOL)

ERIC-PCR DNA fingerprinting patterns were used to identify the isolates occupying nodules. All the isolates nodulated cowpea, groundnut (Arachis hypogeae) and mungbean (Vigna radiata), but only AII-2-1, AII-3-4 and BIII-2-2 nodulated soybean (Glycine max). Apart from cowpea where all the isolates were effective, there ...

Cobalt doped proangiogenic hydroxyapatite for bone tissue engineering application.

Science.gov (United States)

Kulanthaivel, Senthilguru; Roy, Bibhas; Agarwal, Tarun; Giri, Supratim; Pramanik, Krishna; Pal, Kunal; Ray, Sirsendu S; Maiti, Tapas K; Banerjee, Indranil

2016-01-01

The present study delineates the synthesis and characterization of cobalt doped proangiogenic-osteogenic hydroxyapatite. Hydroxyapatite samples, doped with varying concentrations of bivalent cobalt (Co(2+)) were prepared by the ammoniacal precipitation method and the extent of doping was measured by ICP-OES. The crystalline structure of the doped hydroxyapatite samples was confirmed by XRD and FTIR studies. Analysis pertaining to the effect of doped hydroxyapatite on cell cycle progression and proliferation of MG-63 cells revealed that the doping of cobalt supported the cell viability and proliferation up to a threshold limit. Furthermore, such level of doping also induced differentiation of the bone cells, which was evident from the higher expression of differentiation markers (Runx2 and Osterix) and better nodule formation (SEM study). Western blot analysis in conjugation with ELISA study confirmed that the doped HAp samples significantly increased the expression of HIF-1α and VEGF in MG-63 cells. The analysis described here confirms the proangiogenic-osteogenic properties of the cobalt doped hydroxyapatite and indicates its potential application in bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Distribution of nodules and associated features in the Central Indian Basin: observations from seabed photogarphs

Digital Repository Service at National Institute of Oceanography (India)

Sharma, R.

in standard format (SPHINCS) developed for photography data in dBASE III+. The photographic observations have helped in classifying the seafloor, as nodule dominant, sediment dominant and rock dominant, based on the coverage and abundance data; which...

Immunological Reaction in TNF-α-Mediated Osteoclast Formation and Bone Resorption In Vitro and In Vivo

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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.

South African Papilionoid Legumes Are Nodulated by Diverse Burkholderia with Unique Nodulation and Nitrogen-Fixation Loci

Science.gov (United States)

Beukes, Chrizelle W.; Venter, Stephanus N.; Law, Ian J.; Phalane, Francina L.; Steenkamp, Emma T.

2013-01-01

The root-nodule bacteria of legumes endemic to the Cape Floristic Region are largely understudied, even though recent reports suggest the occurrence of nodulating Burkholderia species unique to the region. In this study, we considered the diversity and evolution of nodulating Burkholderia associated with the endemic papilionoid tribes Hypocalypteae and Podalyrieae. We identified distinct groups from verified rhizobial isolates by phylogenetic analyses of the 16S rRNA and recA housekeeping gene regions. In order to gain insight into the evolution of the nodulation and diazotrophy of these rhizobia we analysed the genes encoding NifH and NodA. The majority of these 69 isolates appeared to be unique, potentially representing novel species. Evidence of horizontal gene transfer determining the symbiotic ability of these Cape Floristic Region isolates indicate evolutionary origins distinct from those of nodulating Burkholderia from elsewhere in the world. Overall, our findings suggest that Burkholderia species associated with fynbos legumes are highly diverse and their symbiotic abilities have unique ancestries. It is therefore possible that the evolution of these bacteria is closely linked to the diversification and establishment of legumes characteristic of the Cape Floristic Region. PMID:23874611

Qualitative elastography can replace thyroid nodule fine-needle aspiration in patients with soft thyroid nodules. A systematic review and meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Nell, Sjoerd; Kist, Jakob W. [Department of Surgery, University Medical Center Utrecht (Netherlands); Debray, Thomas P.A. [Julius Center for Health Sciences and Primary Care Utrecht (Netherlands); Keizer, Bart de [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht (Netherlands); Oostenbrugge, Timotheus J. van; Borel Rinkes, Inne H.M. [Department of Surgery, University Medical Center Utrecht (Netherlands); Valk, Gerlof D. [Department of Endocrinology, University Medical Center Utrecht (Netherlands); Vriens, Menno R., E-mail: mvriens@umcutrecht.nl [Department of Surgery, University Medical Center Utrecht (Netherlands)

2015-04-15

Context: Only a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules. Objective: To investigate the diagnostic value of qualitative elastography in distinguishing benign from malignant thyroid nodules in patients referred for fine-needle aspiration (FNA). Data sources: A systematic literature search (PubMed, Embase and Cochrane Library) was performed. Study selection: Included studies reported thyroid nodule elastography color scores and the related cytologic or histologic findings in patients with a thyroid nodule referred for FNA. Data extraction: Two independent reviewers extracted study data and assessed study quality. Pooled sensitivities and specificities of different populations were calculated using a bivariate Bayesian framework. Data Synthesis: Twenty studies including thyroid nodules were analyzed. Pooled results of elastography indicate a summary sensitivity of 85% (95% confidence interval [CI], 79–90%) and specificity of 80% (95% CI, 73–86%). The respective pooled negative predictive and positive predictive values were 97% (95% CI, 94–98%) and 40% (95% CI, 34–48%). The pretest probability of a benign nodule was 82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma. A pooled negative predictive value of 99% (95% CI, 97–100%) was found when only complete soft nodules (Asteria elastography 1) were classified as benign, which included 14% of the studied population. Conclusions: Elastography has a fair specificity and sensitivity for diagnostic accuracy. Its major strength entails the detection of benignity, especially when only completely soft nodules are qualified as benign. The outcomes of our analysis show that FNA could safely be omitted in patients referred for analysis of their thyroid nodule when elastography shows it

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

Science.gov (United States)

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

2012-03-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

Science.gov (United States)

Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Molecular aspects of the nitrogen fixing system in pea root nodules

International Nuclear Information System (INIS)

Bisseling, T.

1980-01-01

The author considers symbiotic nitrogen fixation of Pisum sativum and Rhizobium leguminosarum. Some general aspects of nodule formation and the regulation of the proteins nitrogenase and leghemoglobin (Lb) have been studied. Synthesis of these proteins was studied by 35 SO 4 labelling of intact pea plants. The sequence of appearance of the proteins was determined with specific radioimmunoassays for each protein. (Auth.)

The effect of diabetes on bone formation following application of the GBR principle with the use of titanium domes.

Science.gov (United States)

Lee, Sang-Bok; Retzepi, Maria; Petrie, Aviva; Hakimi, Ahmad-Reza; Schwarz, Frank; Donos, Nikolaos

2013-01-01

The aim of the study was to evaluate the effect of experimental diabetes and metabolic control on de novo bone formation following the GBR principle under titanium dome with a hydrophobic or hydrophilic surface. Three groups of equal number of randomly allocated Wistar strain rats were created: (a) uncontrolled, streptozotocin-induced diabetes (D); (b) insulin-controlled diabetes (CD); (c) healthy (H). Each group was then further divided into two groups according to either 7 or 42 days of healing period, which received either a hydrophobic (SLA: A) or a hydrophilic (SLActive: B) dome. The undecalcified sections were evaluated by qualitative and quantitative histological analysis and the differences between means for the groups (D, CD, and H) and the type of domes (SLA and SLActive) at each of two observational periods (i.e. 7 and 42 days) were assessed by performing a two-way analysis of variance (ANOVA). In all experimental groups, significant de novo bone formation under the domes was observed at 42 days of healing. There was a tendency of increased new total bone (TB) formation in H and CD groups compared to D group at 42 days of healing. Also, the SLActive titanium surface showed a trend of promoting superior TB formation at the early observational period among the experimental groups, however these differences did not reach statistical significance. In regards to the bone-to-implant contact (BIC%) under the both dome treatments (SLA and SLActive), there was no statistically significant difference among the H, CD, and D groups at both 7 and 42 days. Despite of the presence of uncontrolled diabetes, substantial de novo bone formation can be achieved in titanium domes with a hydrophobic and a hydrophilic surface. The use of SLActive titanium surface may present a tendency to promote new bone formation in healthy and diabetic conditions at 7 days of healing, however the obtained data do not allow any robust conclusions. © 2012 John Wiley & Sons A/S.

Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

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Chen-he Zhou

2018-03-01

Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

Mechanisms Inducing Low Bone Density in Duchenne Muscular Dystrophy in Mice and Humans

Science.gov (United States)

Rufo, Anna; Del Fattore, Andrea; Capulli, Mattia; Carvello, Francesco; De Pasquale, Loredana; Ferrari, Serge; Pierroz, Dominique; Morandi, Lucia; De Simone, Michele; Rucci, Nadia; Bertini, Enrico; Bianchi, Maria Luisa; De Benedetti, Fabrizio; Teti, Anna

2011-01-01

Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro–computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. © 2011 American Society for Bone and Mineral Research PMID:21509823

Bone grafts in dentistry

Directory of Open Access Journals (Sweden)

Prasanna Kumar

2013-01-01

Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

Isolate pulmonary nodule. CT-guided biopsy

International Nuclear Information System (INIS)

Bruneton, J.N.; Ettore, F.; Rogopoulos, A.; Geoffray, A.; Balu-Maestro, C.; Le Houcq, M.

1989-01-01

Transparietal CT-guided biopsy location can be successfully performed for isolate pulmonary nodules, defined as lesions with a maximal diameter of 3 cm, without any other parenchymal or mediastinal abnormality. A 21 G needle has been used according to an identical protocole in 64 cases (10 benign, 54 malignant). The biopsy was successful in 77.7% of the malignant cases. In relation to the diameter of the nodules, biopsy was successful in 66.7% of the nodules smaller than 2 cm and in 76% of the nodules ranging from 2 to 3 cm. The complications observed were rare (1 case of pneumothorax requiring drainage, 9 cases of pneumothorax without clinical signs and simply followed up, 4 cases of minor hemoptysis requiring no treatment and 5 cases of hematomas smaller than 5 cm on CT) [fr

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

Directory of Open Access Journals (Sweden)

Yun-Ho Hwang

2018-03-01

Full Text Available Osteoporosis is characterized by a reduction of the bone mineral density (BMD and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP activity. The bone mineral density (BMD and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT c1, dendritic cell-specific transmembrane protein (DC-STAMP, TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs. Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis.

Pulmonary nodule: new concepts of an Old Problem

International Nuclear Information System (INIS)

Diederich, S.; Wormanns, D.

2003-01-01

In the past, a pulmonary nodule was considered malignant until proven otherwise, usually histologically, which frequently required invasive diagnostic procedures. The nodule was mostly detected on conventional chest radiographs and usually larger than 10 mm. Recently, modern (multi-slice) helical CT detects an increasing number of very small (≤ 10 mm) nodules, which are benign in > 95%. Consequently, the exclusion of malignancy demands different diagnostic procedures, which should be predominantly non-invasive. This article presents the current data as well as imaging techniques for the determination of the nature of pulmonary nodules and suggests concepts for the diagnostic approach to small pulmonary nodules. (orig.) [de

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

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.

Management of a solitary thyroid nodule

International Nuclear Information System (INIS)

Rao, R.S.

1999-01-01

Solitary nodule in the thyroid is a common clinical entity. A careful clinical assessment is the crucial first step in deciding the modality of treatment. The only worthwhile investigation is FNAC. Other investigations are done merely for the sake of a complete academic work up and can usually be dispensed with in most of the cases. Not every solitary nodule requires surgery. The optimum surgery for a solitary nodule is a total lobectomy. The specimen should be subjected to histological examination before recommending further treatment

The relationship between inflammation and new bone formation in patients with ankylosing spondylitis.

Science.gov (United States)

Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

2008-01-01

Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondylitis patients treated with anti-tumour necrosis factor (anti-TNF) agents at baseline and after 2 years were analysed for syndesmophyte formation at vertebral edges with or without inflammatory lesions at baseline. Overall, 922 vertebral edges at the cervical and lumbar spine were analysed. At baseline, the proportion of vertebral edges with and without inflammation (magnetic resonance imaging) that showed structural changes (conventional radiographs) was similar (in total, 16.6% of all vertebral edges in 71.4% of patients). From the perspective of syndesmophyte formation (n = 26, 2.9%) after 2 years, there were more vertebral edges without (62%) than with (38%) inflammation at baseline (P = 0.03). From the perspective of spinal inflammation at baseline (n = 153 vertebral edges), more syndesmophytes developed at vertebral edges with (6.5%) than without (2.1%) inflammation (P = 0.002, odds ratio 3.3, 95% confidence interval 1.5 to 7.4). Inflammation persisted in 31% of the initially inflamed vertebral edges (n = 132), and new lesions developed in 8% of the vertebral edges without inflammation at baseline (n = 410). From the perspective of spinal inflammation after 2 years (n = 72 vertebral edges), 5.6% of the vertebral edges showed syndesmophyte development in contrast to 1.9% of the vertebral edges with new syndesmophytes without inflammation (P = 0.06). These findings obtained in patients treated with anti-TNF agents suggest linkage and some dissociation of inflammation and new bone formation in

Effect of polygonimitin C on bone formation and resorption in human ...

African Journals Online (AJOL)

Purpose: To investigate the effect of polygonimitin C (PC) on bone formation and resorption in human osteoblast-like MG63 cells. Methods: MG63 cells were treated with PC at doses of 0, 20, 40 or 80 μg/mL for 48 h, with an untreated group as control. The effect of PC on alkaline phosphatase (ALP) activity in MG63 cells ...

Hollow Nodules Gas Escape Sedimentary Structures in Lacustrine Deposits on Earth and Gale Crater

Science.gov (United States)

Bonaccorsi, R.; Willson, D.; Fairen, A. G.; Baker, L.; McKay, C.; Zent, A.; Mahaffy, P. R.

2015-12-01

Curiosity's Mastcam and MAHLI instruments in Gale Crater (GC) imaged mm-sized circular rimmed hollow nodules (HNs) (Figure 1A), pitting the Sheepbed mudstone of Yellowknife Bay Formation [1,2]. HNs are significantly smaller than the solid nodules within the outcrop, with an external mean diameter of 1.2 mm and an interior one of 0.7 mm [2] Several formation mechanisms of HNs have been discussed, such as: (1) Diagenetic dissolution of soluble mineral phases; or, (2) Gas bubbles released shortly after sediment deposition [1-3]. In an ephemeral pond in Ubehebe Crater (Death Valley, CA) we observed the formation of hollow nodule sedimentary structures produced by gas bubbles (Figure 1C) preserved in smectite-rich mud that are strikingly similar to those imaged in GC (Figure 1A). This finding supports the gas bubble hypothesis [2]. Ubehebe Crater (UC) surface sediment hollow nodules were sampled, imaged, and their internal diameter measured (200 hollow structures) showing similar shape, distribution, and composition to those imaged by Curiosity in GC. UC in-situ observations suggest the gas bubbles were generated within the slightly reducing ephemerally submerged mud. These intra-crater deposits remain otherwise extremely dry year round, i.e., Air_rH ~2-5%; ground H2O wt%: 1-2%; Summer air/ground T: 45-48ºC/67-70ºC [4-5]. Data from the Sample Analysis at Mars (SAM), CheMin, and ChemCam instruments onboard the rover revealed that HNs-bearing mudstone are rich in smectite clay e.g., ~18-20% [6,7] deposited in a neutral to mildly alkaline environment, capturing a period when the surface was potentially habitable [1]. The UC HNs-hosting deposits are also rich in smectite clays (~30%) and occur in an ephemeral shallow freshwater setting [4-5]. If present, surface hollow nodules are easy to find in dry clay-rich mud in lacustrine sediments, so they could represent a new indicator of ephemeral but habitable/inhabited environments on both Earth and early Mars. References: [1

Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.

Science.gov (United States)

Chantarawaratit, P; Sangvanich, P; Banlunara, W; Soontornvipart, K; Thunyakitpisal, P

2014-04-01

Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate