Dysregulated autophagy in osteoarthritis: Mechanisms, regulation by non-coding RNAs, and therapeutic implications.

Osteoarthritis (OA) is a degenerative disease driven by inflammation, cell death, and metabolic changes. Autophagy is known as a cellular recycling process that plays a critical dual role in OA. It protects cartilage by removing damaged parts; however, excessive autophagy induces damages to chondrocytes. The way autophagy is dysregulated in OA was investigated and major areas, including the regulation of autophagy by non-coding RNAs (miRNAs, lncRNAs, circRNAs), the complex interaction of autophagy with cell death pathways such as apoptosis, pyroptosis, ferroptosis, and necroptosis were highlighted. In addition, the therapeutic potential of natural compounds and drugs that target autophagy were assessed. Notably, the protective versus detrimental effects of autophagy, which depends on disease stage and stress intensity, were discussed. Practical limitations, including the poor bioavailability of phytochemicals and the need for nano-delivery systems were highlighted. The paper concludes with proposing future research directions such as exploring autophagy-ferroptosis crosstalk.