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Saidenberg-Kermanac'h N Bessis N Lemeiter D de Vernejoul MC Boissier MC Cohen-Solal M 《Journal of clinical immunology》2004,24(4):370-378
To evaluate the respective action of IL-4, an anti-inflammatory cytokine, and OPG, an inhibitor of bone resorption, on the inflammatory process and the associated bone resorption in collagen-induced arthritis (CIA). After CIA induction, DBA/1 mice were treated with OPG or with IL-4 DBA/1 transfected fibroblasts or both OPG + IL-4. CIA significantly improved in IL-4 groups. OPG had no effect on arthritis clinical scores but histologic scores were reduced in OPG, IL-4, and OPG + IL-4 groups vs. nontreated CIA mice. OPG increased significantly BMD and decreased by 45% D-pyridinolin levels. Moreover association of IL-4 and OPG exerted an additive effect of BMD and resorption marker (-68%). Production of IFN-gamma in the supernatants of spleen cells was reduced in IL-4 treated mice. OPG had a moderate effect on IFN-gamma, but potentiated the inhibitory effect of IL-4. OPG and IL-4 prevent bone loss in CIA-mice model and could have additive effects on IFN-gamma secretion. 相似文献
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T. Neumann P. Oelzner P. K. Petrow K. Thoss G. Hein G. Stein R. Bräuer 《Inflammation research》2006,55(1):32-39
Objective: To assess the effect of osteoprotegerin (OPG) on joint swelling, synovial inflammation and cartilage destruction, periarticular
and axial bone volume, and bone turnover in rat antigen-induced arthritis (AIA). Design: Rats were treated with OPG (3 mg/kg/day) at regular intervals from day 1 to day 20 of AIA. Disease activity was evaluated
by measurement of joint swelling as well as, joint inflammation and destruction by histology. Bone volume and cellular turnover
parameters of secondary spongiosa of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry.
Periarticular bone volume of the primary spongiosa at the right tibia head was measured by linear scanning. The findings were
compared with those of PBS-treated AIA and healthy animals. Result: OPG treatment did not reduce joint swelling or histological signs of inflammation. Cartilage destruction was reduced. However,
this effect did not reach statistical significance . In the secondary spongiosa OPG treatment reduced the loss of periarticular
bone volume. However, the latter did not reach the level of healthy controls. OPG treatment significantly reduced parameters
of bone formation and bone resorption. In the primary spongiosa, OPG-treatment led to a higher amount of mineralized tissue
and a greater number of trabeculae compared to PBS-treated animals with AIA or healthy controls. In the axial skeleton, OPG
treatment reduced bone formation and bone resorption parameters compared to healthy animals. This treatment had no influence
on bone volume. Conclusions: In periarticular bone of AIA rats, OPG treatment reduced the loss of bone volume and decreased the bone turnover, thus preventing
periarticular bone destruction. OPG treatment had no influence on inflammatory process or on cartilage destruction.
Received 2 June 2005; returned for revision 26 July 2005; returned for final revision 9 August 2005; accepted by M. Parnham
24 September 2005
Presented in part at the 66. Annual Meeting of the American College of Rheumatology, New Orleans, U.S.A., October 2002, and
at the 25. Annual Meeting of the American Society of Bone and Mineral Research, Minneapolis, USA, September 2003
Supported by grants from the Thuringian Ministry of Science, Research and Art (B307-01025, B378-01017), the Interdisciplinary
Center for Clinical Research (IZKF) Jena, and the Deutsche Forschungsgemeinschaft (Br 1372/5-1)
Osteoprotegerin was generously provided by Amgen (Thousand Oaks, CA, USA).
Drs. Neumann and Oelzner contributed equally to this work. 相似文献
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Receptor activator of nuclear factor-kappaBligand(RANKL)promotes osteoclast formation,fusion,differentiation and activation.It plays akey role in osteoclast mediated bone erosion inrheumatoid arthritis(RA).Osteoprotegerin(OPG),as a soluble decoy receptor of RANKL,can prevent bone erosion in RA.Our previousstudies have shownthat Triptolide(TP),an activecompoundidentifiedin a traditional Chinese herb--Tripterygium wilfordii Hook F(TWHF),can ef-fectively inhibit bone destruction in ex… 相似文献
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《Expert opinion on investigational drugs》2013,22(8):1085-1102
The receptor activator of NF-κB ligand (RANKL) is a member of the TNF receptor superfamily, essential for osteoclastogenesis. It binds to its receptor activator of NF-κB on the surface of osteoclast precursors and enhances their differentiation, survival and fusion, while it activates mature osteoclasts and inhibits their apoptosis. The effects of RANKL are counteracted by osteoprotegerin (OPG), a neutralizing decoy receptor. Derangement of the balance in RANKL/OPG action is implicated in the pathophysiology of metabolic bone diseases, including osteoporosis. Current therapies used to prevent or treat metabolic bone diseases are thought to act, at least in part, through modification of the RANKL/OPG dipole. The idea of using a molecule that could specifically bind and neutralize RANKL to decrease bone resorption and subsequent bone loss is appealing. Recombinant OPG was initially tested. Denosumab, a fully human monoclonal antibody against RANKL, is a promising antiresorptive agent under investigation. It rapidly decreases bone turnover markers resulting in a significant increase in bone mineral density and reduction in fracture risk. However, because receptor activator of NF-κB activation by RANKL is also essential for T-cell growth and dendritic-cell function, inhibition of its action could simultaneously affect the immune system, leading to susceptibility in infections or malignancies. 相似文献
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Effects of photodynamic therapy in periodontal treatment: A randomized,controlled clinical trial 下载免费PDF全文
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目的:研究香豆雌酚(coumestrol)对膝骨关节炎患者软骨细胞OPG/RANKL及MMP-1、MMP-3表达的影响,初步探讨其对骨关节炎的治疗机制。方法:分离、培养因膝骨关节炎行膝关节置换患者的膝关节软骨细胞,运用Ⅱ型胶原免疫荧光染色进行软骨细胞鉴定。用不同浓度(10-9、10-8、10-7mol·L-1)香豆雌酚干预第3代细胞,并设0浓度为空白对照组,分别于培养后3、7 d用real-time PCR法测定细胞骨保护素(osteoprotegerin,OPG)、核因子κB受体活化因子配基(receptor activator of nuclear factor-κB ligand,RANKL)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)和基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)mRNA的表达。结果:干预3 d,10-8mol·L-1组OPG及RANKL mRNA表达均增加,其OPG/RANKL相对表达是空白对照组的2.59倍(P<0.05);干预7 d,10-9和10-8mol·L-1组OPG mRNA表达均增加,10-7mol·L-1组RANKL mRNA表达增加,10-8mol·L-1组OPG/RANKL相对表达是空白对照组的3.85倍(P<0.05)。干预3 d,10-8mol·L-1组MMP-1 mRNA表达减少(P<0.05);干预7 d,10-8mol·L-1组MMP-1和MMP-3 mRNA表达均减少(P<0.05)。结论:香豆雌酚能增加膝骨关节炎患者关节软骨细胞OPG表达及OPG/RANKL值,减少其MMP-1、MMP-3表达,具有一定的软骨保护作用。 相似文献