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Bone Biology (bone + biology)
Selected AbstractsCARTILAGE IN BONE BIOLOGY AND PATHOPHYSIOLOGYINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2006Article first published online: 6 JUL 200 No abstract is available for this article. [source] In Silico Modeling and Simulation of Bone Biology: A ProposalJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Nadine A Defranoux Abstract Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research. Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease. [source] The pivotal role of the alternative NF-,B pathway in maintenance of basal bone homeostasis and osteoclastogenesis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2010Niroshani S Soysa Abstract The alternative NF-,B pathway consists predominantly of NF-,B-inducing kinase (NIK), I,B kinase , (IKK,), p100/p52, and RelB. The hallmark of the alternative NF-,B signaling is the processing of p100 into p52 through NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of alternative NF-,B activation in bone biology, however, is not well understood. To elucidate the role of the alternative pathway in bone homeostasis, we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and are unable to process p100, resulting in the absence of p52. We observed increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic phenotype. These mice also have a significant defect in RANKL-induced osteoclastogenesis in vitro and in vivo. NF-,B DNA-binding assays revealed reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly osteoclast nuclear extracts after RANKL stimulation. To determine the role of p100 itself without the influence of a concomitant lack of p52, we used p100,/, mice, which specifically lack the p100 inhibitor but still express p52. p100,/, mice have an osteopenic phenotype owing to the increased osteoclast and decreased osteoblast numbers that was rescued by the deletion of one allele of the relB gene. Deletion of both allele of relB resulted in a significantly increased bone mass owing to decreased osteoclast activity and increased osteoblast numbers compared with wild-type (WT) controls, revealing a hitherto unknown role for RelB in bone formation. Our data suggest a pivotal role of the alternative NF-,B pathway, especially of the inhibitory role of p100, in both basal and stimulated osteoclastogenesis and the importance of RelB in both bone formation and resorption. © 2010 American Society for Bone and Mineral Research [source] Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Robert L Jilka Abstract Since the initial demonstration of the phenomenon in murine and human bone sections ,10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls. [source] Materials in particulate form for tissue engineering.JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2007Abstract Materials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application of materials in particulate form for bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented. Copyright © 2007 John Wiley & Sons, Ltd. [source] Metastases and multiple myeloma generate distinct transcriptional footprints in osteocytes in vivo,THE JOURNAL OF PATHOLOGY, Issue 5 2008S Eisenberger Abstract Osteocytes are the most abundant bone cells, playing important roles in tissue maintenance. Little is known of how they react in vivo to cancer stress. Here we present a comparative study of the effect of a bone-residing tumour (myeloma) and metastases of bone-remote cancers on osteocytes. While no differences in morphology of the bone are seen, the changes in the transcriptome of osteocytes are specifically related to the tumour stress present. Screening ,22 000 genes in osteocytes prepared from cryosections of native bone using laser-supported microdissection, we observed ,1400 and ,1800 gene expression differences between osteocytes dissected from normal bone compared with those associated with metastases and multiple myeloma, respectively. The genes up-regulated due to the stress exerted by metastases were repressed by multiple myeloma and vice versa, indicating stress-specific footprints in the transcriptome of osteocytes. Functionally, the stressors seem to impose selective pressures on signalling pathways such as that of TGF,, a major player in bone biology. Our data show for the first time that the transcriptome of osteocytes in vivo becomes strongly affected by cancer stress, generating gene expression footprints which, in contrast to comparable morphological changes, appear to relate to the nature of cancer and might thus become helpful in distinguishing different bone diseases. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] A role for ,/, T cells in a mouse model of fracture healingARTHRITIS & RHEUMATISM, Issue 6 2009Nona T. Colburn Objective Fractures can initiate an immune response that disturbs osteoblastic and osteoclastic cellular homeostasis through cytokine production and release. The aim of our study was to investigate ,/, T cells, innate lymphocytes known to be involved in tissue repair, as potential cellular components of the osteoimmune system's response to an in vivo model of bone injury. The absence of such cells or their effector cytokines influences the fate of other responder cells in proliferation, differentiation, matrix production, and ultimate callus formation. Methods Tibia fractures were created in 60 ,/, T cell,deficient mice (also called , T cell receptor [TCR],knockout mice) and 60 control C57BL/6 mice. Analysis included radiographs, basic histology, mechanical testing, flow cytometry, and immunohistochemical localization of ,/, TCR,positive subsets from control animals and of CD44 expression from both groups, as well as enzyme-linked immunosorbent assay for the effector cytokines interleukin-2 (IL-2), interferon-, (IFN,), and IL-6. Results Animals deficient in ,/, T cells demonstrated more mature histologic elements and quantitative increases in the expression of major bone (bone sialoprotein) and cartilage (type II collagen) matrix proteins and in the expression of bone morphogenetic protein 2 at a critical reparative phase. Moreover, only ,/, T cell,deficient animals had a decrease in the osteoprogenitor antiproliferative cytokines IL-6 and IFN, at the reparative phase. The result was improved stability at the repair site and an overall superior biomechanical strength in ,/, T cell,deficient mice compared with controls. Conclusion The evidence for a role of ,/, T cells in the context of skeletal injury demonstrates the importance of the immune system's effect on bone biology, which is relevant to the field of osteoimmunology, and offers a potential molecular platform from which to develop essential therapeutic strategies. [source] New and emerging treatments for osteoporosisCLINICAL ENDOCRINOLOGY, Issue 3 2009Bart L. Clarke Summary A variety of new treatments for osteoporosis have become available within the last several years, and a number of emerging treatments remain in late clinical stage development. New and emerging treatments include more potent members, or more convenient formulations, of existing classes of therapy, but a number of the emerging treatments are first-generation compounds addressing specific therapeutic targets based on recent advances in understanding of basic bone biology. These new and emerging treatments include agents with anticatabolic effects, compounds with anabolic effects, and one agent possibly containing both anticatabolic and anabolic effects. The increasing variety of new and emerging treatments increases the possibility that effective therapy will be targeted to the specific needs of the individual patient. [source] | ||||||||||