Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy

Osteoarthritis (OA), a chronic degenerative disease with heterogeneous properties, is difficult to cure due to its complex pathogenesis. Curcumin possesses excellent anti-inflammatory and antioxidant properties and may have potential therapeutic value in OA. In this study, we investigated the action targets of curcumin and identified potential anti-OA targets for curcumin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were performed to evaluate these targets. Furthermore, we established a sodium monoiodoacetate-induced rat knee OA model and IL-1 beta induced OA chondrocyte model to verify the effect and mechanism of curcumin against OA. The GO and KEGG analyses screened seven hub genes involved in metabolic processes and the AMPK signaling pathway. Curcumin can significantly attenuate OA characteristics according to Osteoarthritis Research Society International (OARSI) and Mankin scores in OA rats. Additionally, curcumin is notably employed as an activator of mitophagy in maintaining mitochondrial homeostasis (ROS, Ca2+, ATP production, and mitochondrial membrane potential). The expression levels of mitophagy-related proteins were increased not only in articular cartilage but also in chondrocytes with curcumin intervention. Combining validation experiments and network pharmacology, we identified the importance of mitophagy in the curcumin treatment of OA. The chondroprotective effects of curcumin against OA are mediated by the AMPK/ PINK1/Parkin pathway, and curcumin may serve as a potential novel drug for OA management.

Automated summary

Curcumin, with its anti-inflammatory and antioxidant properties, shows potential therapeutic value in the treatment of osteoarthritis. Through analyzing the action targets of curcumin, the study found that curcumin attenuates osteoarthritis characteristics by activating mitophagy. These findings highlight the importance of mitophagy in the treatment of osteoarthritis with curcumin.