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Bone Formation. (bone + formation)
Selected AbstractsIrreversible Perforations in Vertebral Trabeculae?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003X Banse In human cancellous bone, osteoclastic perforations resulting from normal remodeling were generally considered irreversible. In human vertebral samples, examined by backscatter electron microscopy, there was clear evidence of bridging of perforation defects by new bone formation. Hence trabecular perforations may not be irreversible. Introduction: Preservation of the trabecular bone microarchitecture is essential to maintain its load-bearing capacity and prevent fractures. However, during bone remodeling, the osteoclasts may perforate the platelike trabeculae and disconnect the structure. Large perforations (>100 ,m) are generally considered irreversible because there is no surface on which new bone can be laid down. In this work, we investigated the outcome of these perforations on human vertebral cancellous bone. Materials and Methods: Using backscatter electron microscopy, we analyzed 264 vertebral bone samples from the thoracic and lumbar spine of nine subjects (44,88 years old). Nine fields (2 × 1.5 mm) were observed on each block. Several bone structural units (BSUs) were visible on a single trabecula, illustrating a dynamic, historical aspect of bone remodeling. A bridge was defined as a single and recent BSU connecting two segments of trabeculae previously separated by osteoclastic resorption. They were counted and measured (length and breadth, ,m). Results and Conclusion: We observed 396 bridges over 2376 images. By comparison, we found only 15 microcalluses on the same material. The median length of the bridge was 165 ,m (range, 29,869 ,m); 86% being longer than 100 ,m and 35% longer than 200 ,m. Their breadth was 56 ,m (range, 6,255 ,m), but the thinnest were still in construction. Bridges were found in all nine subjects included in the study, suggesting that it is a common feature of normal vertebral bone remodeling. These observations support the hypothesis that perforation could be repaired by new bone formation. and hence, might not be systematically irreversible. [source] Hypoxia suppresses runx2 independent of modeled microgravityJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Christopher Ontiveros Bone loss is a consequence of skeletal unloading as seen in bed rest and space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation. However, the RWV is able to reproduce in a controlled fashion at least two aspects of disuse that are directly linked, model microgravity and hypoxia. Hypoxia in the RWV is indicated by reduced medium oxygen tension and increased expression of GAPDH and VEGF. To uncouple the role of model microgravity from hypoxia in suppressed runx2 expression, we cultured osteoblasts under modeled microgravity (oxygenated, horizontal RWV rotation), hypoxia (vertical RWV rotation), or both conditions (horizontal RWV rotation). The expression, DNA binding activity and promoter activity of runx2, was suppressed under hypoxic but not normoxic modeled microgravity RWV conditions. Consistent with a role for hypoxia in suppression of runx2, direct exposure to hypoxia alone is sufficient to suppress runx2 expression in osteoblasts grown in standard tissue culture plates. Taken together, our findings indicate that hypoxia associated with skeletal unloading could be major suppressor of runx2 expression leading to suppressed osteoblast differentiation and bone formation. © 2004 Wiley-Liss, Inc. [source] Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2009Christine A. Clark Abstract While cyclooxygenases are important in endochondral bone formation during fracture healing, mechanisms involved in prostaglandin E2 (PGE2) regulation of chondrocyte maturation are incompletely understood. The present study was undertaken to determine if PGE2 effects on chondrocyte differentiation are related to modulation of the bone morphogenetic protein (BMP) signaling pathway. In primary murine sternal chondrocytes, PGE2 differentially regulated genes involved in differentiation. PGE2 induced type II collagen and MMP-13, had minimal effects on alkaline phosphatase, and inhibited the expression of the maturational marker, type X collagen. In BMP-2,treated cultures, PGE2 blocked the induction of type X collagen. All four EP receptors were expressed in chondrocytes and tended to be inhibited by BMP-2 treatment. RCJ3.1C5.18 chondrocytes transfected with the protein kinase A (PKA) responsive reporter, CRE-luciferase, showed luciferase induction following exposure to PGE2, consistent with activation of PKA signaling and the presence of the EP2 and EP4 receptors. Both PGE2 and the PKA agonist, dibutyryl cAMP, blocked the induction of the BMP-responsive reporter, 12XSBE, by BMP-2 in RCJ3.1C5.18 chondrocytes. In contrast, PGE2 increased the ability of TGF-, to activate the TGF-,-responsive reporter, 4XSBE. Finally, PGE2 down-regulated BMP-mediated phosphorylation of Smads 1, 5, and 8 in RCJ3.1C5.18 cells and in primary murine sternal chondrocytes. Altogether, the findings show that PGE2 regulates chondrocyte maturation in part by targeting BMP/Smad signaling and suggest an important role for PGE2 in endochondral bone formation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 785,792, 2009 [source] Local injection of thrombin-related peptide (TP508) in PPF/PLGA microparticles,enhanced bone formation during distraction osteogenesisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2008Yan Wang Abstract We have previously demonstrated that injections of the thrombin-related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L -lactic- co -glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508-treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p,<,0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 µg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:539,546, 2008 [source] Rapid quantitative bioassay of osteoinductionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2000Huston Davis Adkisson We developed a reproducible, relatively rapid bioassay that quantitatively correlates with the osteoinductive capacity of demineralized bone matrix obtained from human long bones. We have found that Saos human osteosarcoma cells proliferate in response to incubation with demineralized bone matrix and that an index of this proliferative activity correlates with demineralized bone matrix-induced osteogenesis in vivo. The bioassay (Saos cell proliferation) had an interassay coefficient of variation of 23 ± 2% and an intra-assay cocfficient of 11 ± 1%. Cell proliferation was normalized to a standard sample of demineralized bone matrix with a clinically high osteoinductive capacity, which was assigned a value of one. The Saos cell proliferation for each sample was related to the standard and assigned a value placing it into thc low (0.00-0.39), intermediate (0.40-0.69). or high (0.70-1.49) osteoinductivc index group. Osteoinduction of human demineralized bone matrix was quantitated by expressing new bone formation as a function of the total bone volume (new bone plus the demineralized bone powder). The demineralized bone matrix was placed in pouches formed in the rectus abdominis muscles of athymic rats, and endochondral bone formation was assessed at 35 days following implantation, when marrow spaces in the ossicles were formed by new bone bridging the spaces between demineralized bone matrix particles. The proliferative index correlated with the area of new bone formation in histological sections ol the newly formed ossicles. When the proliferative index (the osteoinductive index) was divided into low, intermediate. and high groups, the correlation between it and new bone formation (osteoinduction) was 0.850 (p < 0.0005) in 25 samples of demineralized bone matrix. There was no overlap in the osteoinduction stimulated between the samples with low and high osteoinductive indices. We conclude that the proliferation assay is useful for the routine screening of bone allograft donors for osteoinductivc potential. Furthermore, the two-dimensional area of new bone formation. as it relates to total new bone area, is a quantitative measure of osteoinduction. [source] | ||||||||||