研究表明钙离子晶体参与了骨性关节炎（OA）的发病，抑制其形成为OA的治疗提供了新的思路。羧化基质GLA蛋白（cMGP）是抑制钙离子晶体形成的重要蛋白，而γ-谷氨酰基羧化酶(GGCX)是MGP羧基化的关键酶。研究表明OA软骨中cMGP降低与GGCX减少有关，我们发现软骨退变程度与GGCX相关，干扰GGCX后正常软骨细胞的凋亡率、MMP13、 X型胶原表达均升高。我们认为GGCX可能通过抑制钙离子晶体形成、调节软骨细胞生物学状态及凋亡对软骨提供保护。本课题应用慢病毒介导GGCX基因进行体内、体外转染的方法研究：1、GGCX对钙离子沉积、软骨钙离子晶体形成及软骨下骨骨组织形态的影响；2、GGCX对软骨细胞凋亡率的影响；3、GGCX对关节液及软骨中cMGP、ucMGP、GGCX、MMP13、 X型及Ⅱ型胶原、TNF、IL-1β表达的影响，多角度探讨其对软骨的保护及作用机制，为临床应用提供理论基础。

Rencent reasearch demonstrated that Ca2+ crystal plays an important role in the pathogenesis of Osteoarthritis, and give rise to the development of novel therapies for the treatment of OA. cMGP was reported to be an important inhibitive protein in the formation of Ca2+ crytal, and GGCX is a key enzyme in the process of carboxylation. Foreign study showed that decrease of cMGP was associated with GGCX. Degeneration of cartilage was found to be related with GGCX in the previous experiment, and interference of GGCX in normal chondrocytes can increase apoptosis rate and expression of MMP13, collagen X. So we hypothesize that GGCX may have certain effect on protection of cartilage through inhibiting formation of Ca2+ crystal and regulating biological status of chondrocyte. In this study, in order to investigate the protective effect on cartilage and mechanism of GGCX from different angles,lentivirus was used to transduct GGCX in vitro and vivo, and then the following subjects will be discussed: 1. influence on Ca2+ deposition, formation of Ca2+ crystals and bone tissue form; 2. effect on apoptosis of OA chondrocyte; 3. expression of cMGP, ucMGP, GGCX, MMP13, collagen X, collagen Ⅱ, TNF and IL-1βin synovial fluid and cartilage also be detected.