Abstract：Objective: To investigate the effects of sinensetin (SIN) on cartilage injury in rheumatoid arthritis (RA) rats via regulating cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) /stimulator of interferon gene (STING) signaling pathway. Methods: A RA rat model was constructed, and successfully modeled rats were randomly separated into a model group (RA group), low and high dose SIN treatment groups (SIN-L, SIN-H groups), and high dose SIN treatment+cGAS/STING signaling pathway activator DMXAA group (SIN-H+DMXAA group), with 12 rats in each group. Additionally, 12 healthy normal rats were selected as the Control group. After 14 days of treatment, the arthritis index (AI) score was performed. Enzyme-linked immunosorbent assay (ELISA) was applied to detect serum levels of inflammatory factors. Hematoxylin and eosin (H&E) staining was applied to detect the pathological morphology of joint tissues. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was applied to detect chondrocyte apoptosis. Immunohistochemistry was applied to detect the expression of cartilage injury related proteins. Western blot was applied to detect the expression of cGAS/STING signaling pathway and apoptosis related proteins in joint tissues. Results: Compared with the Control group, the RA group showed damage to cartilage and bones, uneven surface of articular cartilage, sparse and disordered arrangement of chondrocytes, thickening of synovium, with obvious proliferation of fibrous tissue, and significantly elevated AI score, interleukin 6 (IL-6), IL-17 levels, apoptosis rate, Bax, C-caspase3, matrix metalloproteinase-1 (MMP-1), MMP-3, cGAS, and p-STING/STING expressions (P<0.05). Compared with RA group, the SIN-L and SIN-H groups presented reduced cartilage surface erosion, with more orderly arrangement of chondrocytes and reduced synovial hyperplasia and joint degeneration, and significantly reduced AI score, IL-6, IL-17 levels, apoptosis rate, Bax, C-caspase3, MMP-1, MMP-3, cGAS, and p-STING/STING expression, in a dose-dependent manner (P<0.05). Compared with the SIN-H group, the SIN-H+DMXAA group had more severe pathological damage to cartilage tissue and synovium, and significantly increased AI score, IL-6, IL-17 levels, apoptosis rate, Bax, C-caspase3, MMP-1, MMP-3, cGAS, and p-STING/STING expression (P<0.05). Conclusion: SIN can alleviate cartilage damage in RA rats via the inhibition of the cGAS-STING signaling pathway.
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2025, Vol. 31 
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