Int J Biol Sci 2018; 14(13):1873-1882. doi:10.7150/ijbs.27746 This issue
1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
2. Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, Zhejiang, China
3. Department of Neurosurgery Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
4. Chinese Orthopaedic Regenerative Medicine Society
5. The Second School of Medicine, Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and OA, as well as the therapeutic effects of DHM on mitochondrial homeostasis in TNF-α-treated chondrocytes. The relationship between SIRT3 and OA was confirmed by detecting SIRT3 level in vitro and in vivo. Mitochondrial dysfunction was evaluated in chondrocytes with or without SIRT3 knockdown. Furthermore, the effects of DHM on mitochondrial homeostasis were performed in TNF-α-treated rat chondrocytes in vitro. In this study, our results showed that the SIRT3 level was decreased in mouse OA cartilage, corresponding to the reduced SIRT3 level in TNF-α-treated chondrocytes in vitro. SIRT3 knockdown induced mitochondrial dysfunction in chondrocytes. Moreover, our study demonstrated that DHM might activate SIRT3 to protect rat chondrocytes from TNF-α-induced degeneration and protective effects of DHM on mitochondrial homeostasis in chondrocytes attributed to enhanced SIRT3. Collectively, SIRT3 deficiency is implicated in OA development and DHM exerts anti-degeneration effect by maintaining mitochondrial homeostasis via a SIRT3-dependent manner in chondrocytes.
Keywords: Dihydromyricetin, osteoarthritis, mitochondria, SIRT3