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Bone Degradation (bone + degradation)
Selected AbstractsOsteoclastogenesis, Bone Resorption, and Osteoclast-Based TherapeuticsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2003Mone Zaidi Abstract Over the past decade, advances in molecular tools, stem cell differentiation, osteoclast and osteoblast signaling mechanisms, and genetically manipulated mice models have resulted in major breakthroughs in understanding osteoclast biology. This review focuses on key advances in our understanding of molecular mechanisms underlying the formation, function, and survival of osteoclasts. These include key signals mediating osteoclast differentiation, including PU.1, RANK, CSF-1/c-fms, and src, and key specializations of the osteoclast including HCl secretion driven by H+ -ATPase and the secretion of collagenolytic enzymes including cathepsin K and matrix metalloproteinases (MMPs). These pathways and highly expressed proteins provide targets for specific therapies to modify bone degradation. The main outstanding issues, basic and translational, will be considered in relation to the osteoclast as a target for antiresorptive therapies. [source] The Effects of Soil Environment on Postmortem Interval: A Macroscopic AnalysisJOURNAL OF FORENSIC SCIENCES, Issue 6 2009Kimberley A. Jaggers H.B.Sc. Abstract:, Burial environment, in particular soil moisture, has a significant impact on the type, rate, and extent of bone degradation, which ultimately affects estimations of the postmortem interval (PMI). The purpose of this research is to determine the effects of soil moisture on the color, weight, condition, and texture of bone as it relates to the PMI. Bone changes occurring over two different time intervals (2 and 5 months) were examined using 120 sus scrofa leg bones. During each time interval bones were buried in two soil environments, one of which was drier than the other. The bones in both environments lost weight over time but the net weight loss was greater for bones in the higher moisture environment. There was no change in color, texture, or overall condition, indicating that 150 days is not long enough for such alterations to occur, regardless of the moisture level of the burial environment. [source] Inhibitor of DNA binding/differentiation 2 induced by hypoxia promotes synovial fibroblast,dependent osteoclastogenesisARTHRITIS & RHEUMATISM, Issue 12 2009Mariola Kurowska-Stolarska Objective To map hypoxic areas in arthritic synovium and to establish the relevance of low oxygen levels to the phenotype of synovial fibroblasts, with special focus on bone degradation. Methods To analyze the distribution of hypoxia in arthritic joints, the hypoxia marker EF5 was administered to mice with collagen-induced arthritis (CIA). To evaluate the effect of hypoxia on rheumatoid arthritis synovial fibroblasts (RASFs), reverse suppression subtractive hybridization and complementary DNA array were used. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to evaluate the expression of inhibitor of DNA binding/differentiation 2 (ID-2). To investigate the function of ID-2 in RASFs, cells were transfected either with ID-2 vector or with ID-2,specific small interfering RNA. Results EF5 staining showed the presence of hypoxia in arthritic joints, particularly at sites of synovial invasion into bone. Differential expression analysis revealed that ID-2 was strongly induced by hypoxia in RASFs. Immunohistochemical analysis of CIA mouse synovium and human RA synovium showed a strong expression of ID-2 by RASFs at sites of synovial invasion into bone. Overexpression of ID-2 in RASFs significantly induced the expression of several factors promoting osteoclastogenesis. The biologic relevance of the potent osteoclastogenesis-promoting effects was shown by coculture assays of ID-2,overexpressing RASFs with bone marrow cells, leading to an increased differentiation of osteoclasts from bone marrow precursors. Conclusion The data show that hypoxic conditions are present at sites of inflammation and synovial invasion into bone in arthritic synovium. Hypoxia-induced ID-2 may contribute to joint destruction in RA patients by promoting synovial fibroblast,dependent osteoclastogenesis. [source] The critical role of kinase activity of interleukin-1 receptor,associated kinase 4 in animal models of joint inflammationARTHRITIS & RHEUMATISM, Issue 6 2009Magdalena Koziczak-Holbro Objective We have previously reported that the kinase activity of interleukin-1 receptor,associated kinase 4 (IRAK-4) is important for Toll-like receptor and interleukin-1 receptor signaling in vitro. Using mice devoid of IRAK-4 kinase activity (IRAK-4 KD mice), we undertook this study to determine the importance of IRAK-4 kinase function in complex disease models of joint inflammation. Methods IRAK-4 KD mice were subjected to serum transfer,induced (K/BxN) arthritis, and migration of transferred spleen lymphocytes into joints and cartilage and bone degradation were assessed. T cell response in vivo was tested in antigen-induced arthritis (AIA) by measuring the T cell,dependent antigen-specific IgG production and frequency of antigen-specific T cells in the spleen and lymph nodes. T cell allogeneic response was tested in vitro by mixed lymphocyte reaction (MLR). Results Lipopolysaccharide-induced local neutrophil influx into subcutaneous air pouches was impaired in IRAK-4 KD mice. These mice were also protected from inflammation in the K/BxN and AIA models, as shown by reduced swelling of joints. Histologic analysis of joints of K/BxN serum,injected mice revealed that bone erosion, osteoclast formation, and cartilage matrix proteoglycan loss were reduced in IRAK-4 KD mice. Assessment of T cell response by MLR, by frequency of antigen-specific clones, and by production of antigen-specific IgG did not reveal substantial differences between IRAK-4 KD and wild-type mice. Conclusion These results demonstrate that IRAK-4 is a key component for the development of proarthritis inflammation, but that it is not crucial for T cell activation. Therefore, the kinase function of IRAK-4 appears to be an attractive therapeutic target in chronic inflammation. [source] Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in miceARTHRITIS & RHEUMATISM, Issue 1 2009Marjolein A. van Maanen Objective The parasympathetic nervous system, through the vagus nerve, can down-regulate inflammation in vivo by decreasing the release of cytokines, including tumor necrosis factor , (TNF,), by activated macrophages. The vagus nerve may exert antiinflammatory actions via a specific effect of its principal neurotransmitter, acetylcholine, on the ,7 subunit of nicotinic acetylcholine receptors (,7nAChR) on macrophages. The present study was undertaken to obtain insight into the role of the cholinergic antiinflammatory pathway in arthritis. Methods To inhibit the cholinergic antiinflammatory pathway, mice were subjected to unilateral cervical vagotomy or sham surgery, after which arthritis was induced with type II collagen. In a separate study, nicotine was added to the drinking water of mice with collagen-induced arthritis (CIA). In addition, we investigated the effects of intraperitoneally (IP),injected nicotine and the specific ,7nAChR agonist AR-R17779. Results Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNF, expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNF, levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction. Conclusion These data provide the first evidence of a role of the cholinergic antiinflammatory pathway in the murine CIA model of rheumatoid arthritis. [source] The Effect of Oxcarbazepine on Bone MetabolismACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009Y. Çetinkaya Objective,,, Long term use of several antiepileptic drugs is known to cause alteration in bone metabolism. Therefore, we investigated the effect of new antiepileptic drug, oxcarbazepine, on bone metabolism. Methods,,, Twenty eight patients who were on oxcarbazepin therapy (18 female, 10 males; mean age: 27.82 ± 10.98 years (range: 15,45)) with no additional antiepileptic drug use history in one year period prior to the study and 28 control subjects were involved in the study. Measurement of calcium, phosphate, alkaline phosphatase and Vitamin D3 levels and bone density measurements with DEXA method were performed in patient and age-matched control groups. The baseline parameters were compared with the control group and with those measured at the end of one year. Results,,, The biochemical (calcium, phosphate, alkaline phosphatase and Vitamin D3) parameters and densitometry values after one year of therapy were not different than the baseline values indicating that those were not affected by the therapy (P > 0.05). Conclusions,,, In previous studies, anticonvulsant drugs that induce enzymes increase bone degradation by causing vitamin D deficiency. According to the results of this study, oxcarbazepin with little effect on enzyme induction was shown not to affect bone mineral metabolism. [source] | ||||||||||