To investigate the role of a novel circular RNA, circ_0136474, in regulating chondrocyte autophagy in osteoarthritis (OA) and explore its potential mechanism in OA prevention and treatment, in order to provide a new theoretical basis for clinical treatment.

The SW1353 chondrocyte cell line was used to establish an OA cell model, and BALB/c mice were used to establish an OA mouse model. The expression level of circ_0136474 was detected by qRT-PCR, and autophagy-related proteins were analyzed using Western blot (WB). Safranin O-fast green staining was used to observe the pathological changes in cartilage tissue. A specific shRNA targeting circ_0136474 was used to knock down circ_0136474 in SW1353 cells, and the dynamic changes of autophagosomes and autolysosomes were analyzed using immunofluorescence and the autophagy double marker lentivirus mRFP-GFP-LC3. In addition, an AAV virus was used to establish a circ_0136474 knockdown mouse model to evaluate joint damage and the changes in chondrocyte autophagy levels.

HE staining showed that the joint cartilage structure in the control group was intact, with a smooth and clear surface, while the cartilage in the OA group had disrupted surface integrity and disordered arrangement of chondrocytes. Safranin O-fast green staining revealed a significant loss of chondrocytes in OA mice. The OARSI score showed a significant increase in the OA group. Circ_0136474 expression was upregulated in the OA mouse model. Meanwhile, in the OA model, the expression levels of LC3BII/I and Beclin-1 were significantly decreased, and p62 expression was increased. Silencing circ_0136474 in both cell and animal models resulted in a significant decrease in circ_0136474 levels and restoration of autophagy. Pathological examination showed that in the circ_0136474 silencing group, the cartilage surface was more intact, the chondrocytes were more orderly arranged, the OARSI score significantly decreased, and the number of chondrocytes increased.

Both in vivo and in vitro experiments confirmed the abnormal expression of circ_0136474 in OA model chondrocytes. Ssilencing circ_0136474 in chondrocytes enhanced autophagy levels in OA and alleviated cartilage damage in OA. This finding provides a new theoretical basis for the prevention and treatment of OA.