研究一种新型环状RNA—Circ_0136474在骨关节炎（OA）软骨细胞自噬调控中的作用，探索其对OA防治的潜在机制，为临床治疗提供新的理论依据。

SW1353软骨细胞系构建OA细胞模型，BALB/c小鼠构建OA小鼠模型。通过qRT-PCR检测Circ_0136474的表达水平，利用Western blot（WB）分析自噬相关蛋白的变化，采用番红固绿染色观察软骨组织的病理变化。使用特异性靶向circ_0136474的shRNA构建SW1353细胞的circ_0136474敲除模型，并通过免疫荧光实验和自噬双标慢病毒mRFP-GFP-LC3分析自噬体和自噬溶酶体的动态变化。此外，采用AAV病毒构建circ_0136474敲除小鼠模型，评估关节损伤程度及软骨组织自噬水平的变化。

HE染色结果显示，对照组的关节软骨结构完整，表面光滑清晰，而OA组关节软骨表面完整性遭到破坏，软骨细胞排列紊乱。番红固绿染色结果显示OA小鼠软骨细胞显著丧失，OARSI评分结果表明OA组的评分明显升高。Circ_0136474在OA小鼠模型中表现出上调趋势；与此同时，OA模型中LC3BII/I和Beclin-1的表达水平显著下降，p62的表达水平上升。通过在细胞和动物模型中沉默circ_0136474，发现circ_0136474水平显著下降，且自噬水平得以恢复。病理学检查显示，circ_0136474沉默组关节软骨表面更为完整，软骨细胞排列较为规整，OARSI评分显著降低，软骨细胞的数量明显增多。

体内外实验验证了circ_0136474在OA模型软骨细胞中的异常表达，实验结果显示沉默软骨细胞中的circ_0136474，可增强OA中自噬水平，缓解OA中的软骨破坏。这一发现为OA的预防与治疗提供了新的理论依据。

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.