Biological roles and therapeutic potential of circular RNAs in osteoarthritis

Osteoarthritis (OA) is a common and disabling joint disorder that is mainly characterized by cartilage degeneration and narrow joint spaces. The regulatory functions of non-coding RNAs (long non-coding RNAs, microRNAs [miRNAs], and circular RNAs [circRNAs]) in OA progression have attracted considerable attention, and the function of circular RNAs in the context of OA has been an increasingly popular research topic in the last 6 years. Recent studies have reported that various circRNAs can delay or aggravate diverse aspects of the OA process, including extracellular matrix formation, apoptosis, proliferation, inflammation, and autophagy, via circRNA/miRNA/mRNA pathways. Thus, circRNAs and related pathways are potential therapeutic targets for OA. Our review provides comprehensive information about circRNAs, including their biogenesis, functions, and characteristics, and it reveals their critical roles in the pathogenesis of OA via a large regulatory network of sponges. Considering their regulatory functions and characteristics, we hypothesize that circRNAs not only can be transferred through bodily fluids to serve as diagnostic biomarkers, but they can also be released from mesenchymal stem cell-derived exosomes and delivered to OA chondrocytes acting as therapeutic circRNAs. Further investigations of the in-depth molecular mechanisms of action of circRNAs in OA are expected to provide effective and safe OA treatment strategies.