Osteoarthritis (OA), an age-related joint disease characterized by cartilage degeneration, presents significant therapeutic challenges owing to its multifaceted pathogenesis. Lentinan (LNT), a β-(1,3)-glucan extracted from Lentinus edodes, has been demonstrated to possess multiple biological properties, including antioxidant and anti-inflammatory activities. Notably, the underlying mechanisms for its protective effects against OA remain unknown. The aim of this study was to investigate the therapeutic efficacy and mechanisms of LNT on OA. The effects of LNT on extracellular matrix (ECM), cellular senescence, apoptosis and inflammation were assessed in IL-1β induced chondrocytes. RNA sequencing analysis was subsequently performed to explore the mechanism of LNT, and the regulatory effects of LNT on mitophagy and the mTOR pathway were detected. The effects of LNT were further validated in a rat OA model with anterior cruciate ligament transection (ACLT). We found that LNT alleviated extracellular matrix degradation, chondrocyte senescence, apoptosis and inflammatory factors secretion induced by IL-1β. Mechanistically, LNT promoted mitophagy through activation of the PINK1/Parkin pathway, thereby maintaining mitochondrial homeostasis and protecting chondrocytes. Notably, this protective effect of LNT was suppressed upon treatment with an mTOR agonist. Moreover, LNT suppressed cartilage degeneration in ACLT-induced OA rats. In conclusion, LNT enhanced chondrocyte mitophagy through the mTOR/PINK1/Parkin pathway, thereby mitigating chondrocyte degeneration and delaying OA progression. Consequently, LNT may contribute to the development of new potential strategies for OA treatment.
Lentinan rewrites extracellular matrix homeostasis by activating mitophagy via mTOR/PINK1/Parkin pathway in cartilage to alleviating osteoarthritis.
Qi Li,Hanwen Gu,Kangle Song,Xiangzhen Kong,Yanlin Li,Zhenchuan Liu,Qunbo Meng,Kaiwen Liu,Xiuqi Li,Qing Xie,Leixiang Han,Junhao Lin
Published 2025 in International Journal of Biological Macromolecules
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- Publication year
2025
- Venue
International Journal of Biological Macromolecules
- Publication date
2025-08-15
- Fields of study
Medicine, Materials Science, Environmental Science
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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