骨关节炎(OA)是一种常见的关节退行性疾病，其发病机理尚不十分清楚，骨桥蛋白（OPN）是目前的研究热点之一。申请者以往的研究发现OA模型关节滑液中凝血酶裂解OPN（OPN-N）与OA严重程度密切相关。结合国内外其他文献，推测OPN-N较之完整的OPN（OPN-FL）在OA中有着更重要的作用，其机制可能是由凝血酶切割后暴露出的隐蔽抗原表位SVVYGLR结合软骨细胞、滑膜细胞与破骨细胞表面的整合素受体α9β1，从而影响相关细胞的功能。本研究拟通过体内体外实验，采用基因突变、基因敲除、抗体干预和基因蛋白检测等方法，比较OA患者与正常人相关组织和细胞OPN-FL、OPN-N、α9β1的表达水平及其与病程的相关性，验证OPN-N与α9β1结合从而调控相关细胞的功能，进一步探讨抗OPN-N或抗α9β1抗体对OA的防治效应。旨在从新的视角揭示OA的发病机理，探索新的生物学靶点，为临床防治OA提供新思路。

Osteoarthritis (OA) is thought to be the most prevalent degenerative joint disease. The definite etiology and pathogenesis has not been illustrated clearly. We have found that thrombin-cleaved osteopontin (OPN-N) levels in synovial fluid are closely related to disease severity in the OA rabbit model. Combined with other literatures, we hypothesized that OPN-N might play a greater role than full length OPN (OPN-FL) in the pathogenesis of OA since the SVVYGLR sequence, exposed by thrombin cleavage of OPN-FL, may interact with α9β1 integrin expressed by chondrocyte, synoviocyte and osteoclast, which further regulates cellular function. This study aims to explore: 1) the differences of OPN-FL, OPN-N and α9β1 expression between OA patients and healthy people; 2) the effect of OPN-N in combination with α9β1 in regulating cell functions in vitro; 3) the protective and therapeutic effects of antibodies against OPN-N and α9β1 in vivo, through a series of methods including gene mutation and knockout, gene and protein detection and antibody intervention et al. This research attempts to reveal pathogenesis of OA, explore new therapeutic target, to provide some new ideas on the treatment of OA in the clinical practice.