Hydrogen (H 2 ) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway

Background: Articular cartilage degeneration is considered as one of the major causes of osteoarthritis (OA) which causes joint pain. Hydrogen (H2), has been reported to have a diversity of effects such as anti-apoptotic, anti-inflammatory, and anti-oxidative properties. Hydrogen (H2) shown its anti-inflammatory and anti-apoptotic effects on acute hepatic injury in acute necrotizing pancreatitis via the JNK pathway in the previous study. However, whether Hydrogen (H2) has a protective effect against OA via the JNK signaling pathway remains unknown. Methods: Western blotting, Immunohistochemical assay, immunofluorescence staining, Cell Counting Kit-8, TUNEL staining, and q-RT PCR were performed to investigate the molecular mechanism of Hydrogen (H2) in TBHP-induced human chondrocytes. The therapeutic potential of Hydrogen (H2) was demonstrated by using a destabilized medial meniscus (DMM) mouse OA model. Findings: We found Hydrogen (H2) decreased the production of apoptotic factors (Cleaved caspase-3 and Bax) and inflammation mediators (MMP-13 and ADAMTS-5) in TBHP-driven chondrocytes. Furthermore, Hydrogen (H2) was found to specifically inhibit the activation of the JNK signaling pathway, which could be reversed by Anisomycin (a JNK inhibitor). Besides, the protective effect of Hydrogen (H2) on OA was also observed in the mouse DMM model. Interpretation: This study uncovered that Hydrogen (H2) could ameliorate the development of OA via the JNK signaling pathway, which indicates Hydrogen (H2) as a potential therapeutic agent for OA. Funding: This work was supported by the Science and Technology Department of Zhejiang Province (LY16H060010). Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The protocols of animal use and care and the experimental procedures were accord with the Animal Care and Use Committee of Wenzhou Medical University (ethic code: wydw2019-0808) Human articular cartilage tissue collection with OA was performed by the Medical Ethical Committee of the Second Affiliated Hospital (ethic cord: LCKY2019-67), Wenzhou Medical University and followed the guidelines of the Declaration of Helsinki and Tokyo.