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.

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) and osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis and function is important. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, functions to maintain mitochondrial quality control and homeostasis. IVDD and OA are similar joint diseases involving the degradation of cartilaginous tissues that are mainly caused by oxidative stress, cell apoptosis and extracellular matrix (ECM) degradation. Over the past decade, accumulating evidence indicates the essential role of mitophagy in the pathogenesis of IVDD and OA. Importantly, strategies by the regulation of mitophagy exert beneficial effects in the pre-clinical experiments. Given the importance and novelty of mitophagy, we provide an overview of mitophagy pathways and discuss the roles of mitophagy in IVDD and OA. We also highlight the potential of targeting mitophagy for the treatment of degenerative joint diseases.

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