膝骨关节炎（KOA）尚无特效治法，中医认为该病以肝肾亏虚为本，我们在临床运用龟鹿二仙胶治疗取得良好疗效。软骨细胞凋亡和细胞外基质（ECM）过度降解是KOA发生的重要环节，前期研究证实龟鹿二仙胶可促进软骨细胞增殖和活性、抑制或逆转其凋亡，但龟鹿二仙胶促进退化的软骨细胞增殖明显高于正常软骨细胞的机制还不明确；龟鹿二仙胶调节软骨细胞和ECM分解合成代谢平衡的关键还未完全阐明。最新研究表明退化中的软骨细胞凋亡与自噬可相互协调、共同改善关节软骨退化。本研究拟建立软骨特异mTOR-KO小鼠骨关节炎模型，观察龟鹿二仙胶通过ULK1/AMPK/mTOR通路调控软骨细胞自噬的机制，以证实龟鹿二仙胶是通过调节mTOR表达以激活AMPK/mTOR/ULK-1通路发生自噬，从而促进退化过程中的软骨细胞增殖，抑制或逆转凋亡，调节软骨细胞及ECM的合成和分解代谢平衡，改善软骨细胞内环境稳态，起到保护关节软骨的作用。

Knee osteoarthritis(KOA) is one of the most frequent chronic disease which nowadays has no effective treatment on it.In traditional Chinese medicine,it is believed that KOA is based on yin deficiency of liver and kidney. As we all know,chondrocyte apoptosis and extracellular matrix (ECM) excessively degradation are the main cause of the pathogenesis of KOA. In our previous studies,we have we have confirmed GUILU ERXIAN gelatin had a good clinical effect,and it can promote the degradation of cartilage proliferation and inhibit apoptosis, but it is still uncertain that why this function in KOA cartilage is better than in the normal .The key to regulating the balance between catabolic and anabolic of ECM and chondrocyte remains to be elucidated.Recent studies have shown that the apoptosis and autophagy of degenerative chondrocytes can coordinate with each other and jointly reduce the degradation of articular cartilage.We intend to create cartilage-specific mTOR knockout (KO) mice to observe the machanism of GUILU ERXIAN gelatin to upregulate chondrocyte autophagy signaling by decreasing the expression of mTOR in KOA pathophysiology .And we also want to confirm that whether AMPK/mTOR/ULK-1 is the pathway to induce autophagy to promote KOA chondrocyte proliferation , inhibit chondrocyte apoptosis and keep the balance between catabolic and anabolic of ECM, then finnally protect the articular cartilage by improve cartilage cells homeostasis.