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随着人口老龄化问题的加剧,骨质疏松症的高发生率降低了人们的生活质量。越来越多的证据表明,肠道微生物群与骨代谢联系密切,肠道微生物群稳态的破坏会导致宿主的病理生理反应,从而引起骨质疏松。通过研究两者之间的相互作用,或许能为骨质疏松症的预防及相关诊疗提供有价值的帮助。本文就目前肠道微生物与骨质疏松症相关机制和主要治疗的研究现状作一综述。 相似文献
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Nanjundaiah SM Venkatesha SH Yu H Tong L Stains JP Moudgil KD 《The Journal of biological chemistry》2012,287(26):22216-22226
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone erosion and cartilage destruction in the joints. Many of the conventional antiarthritic drugs are effective in suppressing inflammation, but they do not offer protection against bone damage. Furthermore, the prolonged use of these drugs is associated with severe adverse reactions. Thus, new therapeutic agents that can control both inflammation and bone damage but with minimal side effects are sought. Celastrus is a Chinese herb that has been used for centuries in folk medicine for the treatment of various inflammatory diseases. However, its utility for protection against inflammation-induced bone damage in arthritis and the mechanisms involved therein have not been examined. We tested celastrus and its bioactive component celastrol for this attribute in the adjuvant-induced arthritis model of RA. The treatment of arthritic rats with celastrus/celastrol suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints as demonstrated by histology and bone histomorphometry. The protective effects against bone damage are mediated primarily via the inhibition of defined mediators of osteoclastic bone remodeling (e.g. receptor activator of nuclear factor-κB ligand (RANKL)), the deviation of RANKL/osteoprotegerin ratio in favor of antiosteoclastic activity, and the reduction in osteoclast numbers. Furthermore, both the upstream inducers (proinflammatory cytokines) and the downstream effectors (MMP-9) of the osteoclastogenic mediators were altered. Thus, celastrus and celastrol controlled inflammation-induced bone damage by modulating the osteoimmune cross-talk. These natural products deserve further consideration and evaluation as adjuncts to conventional therapy for RA. 相似文献
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Rendina E Lim YF Marlow D Wang Y Clarke SL Kuvibidila S Lucas EA Smith BJ 《The Journal of nutritional biochemistry》2012,23(1):60-68
This study was designed to investigate the effects of dried plum on the changes in bone metabolism and the immune response associated with ovarian hormone deficiency. Adult female C57BL/6J mice were either sham-operated (Sham) and fed AIN-93 diet (control) or ovariectomized (OVX) and fed a control diet with 0%, 5%, 15% or 25% dried plum (w/w), corresponding to control, low- (LDP), medium- (MDP) and high (HDP)-dose dried plum. Four weeks of HDP supplementation prevented the decrease in spine bone mineral density and content induced by OVX. The OVX compromise in trabecular bone of the vertebra and proximal tibia was prevented by the higher doses of dried plum, and in the vertebra these effects resulted in greater (P<.05) bone strength and stiffness. In the bone marrow, OVX suppressed granulocyte and committed monocyte populations and increased the lymphoblast population, but the MDP and HDP restored these myeloid and lymphoid populations to the level of the Sham. Dried plum also suppressed lymphocyte tumor necrosis factor (TNF)-α production ex vivo by splenocytes, in response to concanavalin (Con) A stimulation. These data indicate that dried plum's positive effects on bone structural and biomechanical properties coincide with the restoration of certain bone marrow myeloid and lymphoid populations, and suppressed splenocyte activation occurring with ovarian hormone deficiency. 相似文献
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Mikihito Hayashi Tomoki Nakashima Tatsuhiko Kodama Noriko Toyama-Sorimachi 《Biochemical and biophysical research communications》2010,393(3):432-625
Osteoclasts, multinucleated cells that resorb bone, play a key role in bone remodeling. Although immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling is critical for osteoclast differentiation, the significance of immunoreceptor tyrosine-based inhibitory motif (ITIM) has not been well understood. Here we report the function of Ly49Q, an Ly49 family member possessing an ITIM motif, in osteoclastogenesis. Ly49Q is selectively induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation in bone marrow-derived monocyte/macrophage precursor cells (BMMs) among the Ly49 family of NK receptors. The knockdown of Ly49Q resulted in a significant reduction in the RANKL-induced formation of tartrate-resistance acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a decreased expression of osteoclast-specific genes such as Nfatc1, Tm7sf4, Oscar, Ctsk, and Acp5. Osteoclastogenesis was also significantly impaired in Ly49Q-deficient cells in vitro. The inhibitory effect of Ly49Q-deficiency may be explained by the finding that Ly49Q competed for the association of Src-homology domain-2 phosphatase-1 (SHP-1) with paired immunoglobulin-like receptor-B (PIR-B), an ITIM-bearing receptor which negatively regulates osteoclast differentiation. Unexpectedly, Ly49Q deficiency did not lead to impaired osteoclast formation in vivo, suggesting the existence of a compensatory mechanism. This study provides an example in which an ITIM-bearing receptor functions as a positive regulator of osteoclast differentiation. 相似文献
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Investigation into arthritis, as well as numerous bone phenotypes found in mice lacking immune-related genes, has highlighted the importance of the interplay between the bone and immune systems, which has led to the emergence and evolution of the field of osteoimmunology. RANKL stimulates osteoclastogenesis through nuclear factor of activated T cells (NFAT) c1, which is also a crucial regulator of immunity. In rheumatoid arthritis, bone destruction is caused by the enhanced activity of osteoclasts, which is mainly dependent on interleukin-17-producing helper T cells (TH17). The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions. The framework of osteoimmunology will provide a scientific basis for future therapeutic approaches to diseases related to both of these systems. 相似文献
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