脂肪因子apelin在骨关节炎中的作用及其机制

Osteoarthritis (osteoarthritis, OA) is a common orthopedic and frequently-occurring disease. The cause of OA is still unknown. The most typical pathological features of OA are apoptosis of chondrocyte, destruction of cartilage matrix and ossification of subchondral bone. Previous studies have shown that the classical adipokines play important roles in degradation of articular cartilage, such as leptin and adiponectin. Till now, little is known about the relationship of apelin and OA. Our previous study found that: The apelin and APJ transcripts were identified in chondrocytes, and levels were significantly higher in OA cartilage than in healthy donors. OA synovial fluid exhibited elevated levels of apelin. Apelin can affect the degrading enzymes in chondrocytes and mediate the pathological processes involved in cartilage destruction. In this study, we take clinical specimens, human cell and animal OA model as object to further investigate the mechanism of osteoblast differentiation and angiogenesis of subchondral bone and synovial regulation by apelin. Signaling pathway inhibitor、RNA interference as well as micro-CT were used in the present study. Our study will further reveal the pathogenesis of OA, and provide new ideas for exploring diseases modifying drugs for OA.

骨关节炎（osteoarthritis, OA）是骨科的一种常见病和多发病，其发病机制仍不清楚。软骨细胞凋亡、软骨基质破坏、软骨下骨骨化是OA最典型的病理特征之一。既往研究表明经典的脂肪因子在OA的关节软骨退化方面起着重要的作用，如瘦素、脂联素。关于新型的脂肪因子apelin的研究报告甚少。我们的前期研究发现：OA患者软骨细胞中高度表达apelin和APJ，OA患者关节滑液中apelin升高，并可影响软骨细胞中降解酶系统，介导参与了软骨破坏的病理过程。本课题以临床标本、动物OA模型及细胞为研究对象，应用信号通路抑制剂、RNA干扰和动物micro-CT等方法进一步研究apelin对OA病理过程中软骨下骨成骨细胞分化及骨代谢中信号通路的作用机制，并观察apelin对软骨下骨及滑膜血管生成的调控。本课题将进一步揭示apelin在骨关节系统中的作用，从而为寻找治疗OA的新途径提供实验依据。

骨关节炎（osteoarthritis, OA）是骨科的一种常见病和多发病，其发病机制仍不清楚。软骨细胞凋亡、软骨基质破坏、软骨下骨骨化是OA 最典型的病理特征之一。既往研究表明经典的脂肪因子在OA 的关节软骨退化方面起着重要的作用，如瘦素、脂联素。关于新型的脂肪因子apelin 的研究报告甚少。我们的前期研究发现：OA患者软骨细胞中高度表达apelin和APJ，OA患者关节滑液中apelin升高，并可影响软骨细胞中降解酶系统，介导参与了软骨破坏的病理过程。本课题通过体外培养成骨细胞，采用siRNA干扰、RT-PCR、western blotting及流式细胞检测等技术，来进一步研究apelin对OA病理过程中软骨下骨成骨细胞分化及骨代谢中信号通路的作用机制。我们的研究发现，apelin能促使成骨细胞分泌大量的降解因子，如MMP-3、MMP-9及ADAMTS-4，而加入APJ siRNA后能有效的抑制此效应。此外，我们还检测 apelin对成骨指标如COLI、ALP、osteopontin、osteocalcin,、RANKL及OPG的影响。通过RT-PCR与western blotting技术，apelin能明显上调ALP、OPN及RANKL的基因及蛋白水平，而对COLI及OCN无明显影响。ELISA测试OPG的水平后，我们发现apelin能轻度抑制OPG的表达，但与对照组相比无明显差异。进一步的流式细胞检测表明了apelin能明显刺激成骨细胞膜上RANKL的表达，表明了apelin能通过OPG/RANKL/RANK，促进破骨细胞活化从而加剧软骨下骨骨量丢失。