Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
The Center for Biomedical Research, The Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China.
Osteoarthritis Cartilage. 2020 Apr;28(4):400-409. doi: 10.1016/j.joca.2020.02.027. Epub 2020 Feb 18.
Osteoarthritis (OA) is a complicated degenerative disease that affects whole joint tissue. Currently, apart from surgical approaches to treat late stage OA, effective treatments to reverse OA are not available. Thus, the mechanisms leading to OA, and more effective approaches to treat OA should be investigated. According to available evidence, the PI3K/AKT/mTOR signaling pathway is essential for normal metabolism of joint tissues, but is also involved in development of OA. To provide a wide viewpoint to roles of PI3K/AKT/mTOR signaling pathway in osteoarthritis, a comprehensive literature search was performed using PubMed terms 'PI3K OR AKT OR mTOR' and 'osteoarthritis'. This review highlights the role of PI3K/AKT/mTOR signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation, and discusses how this signaling pathway affects development of the disease. We also summarize recent evidences of therapeutic approaches to treat OA by targeting the PI3K/AKT/mTOR pathway, and discuss potential challenges in developing these strategies for clinical treatment of OA.
骨关节炎（OA）是一种影响整个关节组织的复杂退行性疾病。目前，除了手术方法治疗晚期 OA 外，尚无有效的逆转 OA 的治疗方法。因此，应该研究导致 OA 的机制以及更有效的 OA 治疗方法。根据现有证据，PI3K/AKT/mTOR 信号通路对于关节组织的正常代谢是必需的，但也参与 OA 的发生。为了从更广泛的角度了解 PI3K/AKT/mTOR 信号通路在骨关节炎中的作用，我们使用 PubMed 术语“PI3K 或 AKT 或 mTOR”和“骨关节炎”进行了全面的文献检索。本综述强调了 PI3K/AKT/mTOR 信号在软骨降解、软骨下骨功能障碍和滑膜炎症中的作用，并讨论了该信号通路如何影响疾病的发展。我们还总结了最近通过靶向 PI3K/AKT/mTOR 通路治疗 OA 的治疗方法的证据，并讨论了将这些策略开发用于 OA 临床治疗的潜在挑战。
