AdipoRon ameliorates synovial inflammatory lesions and joint destruction in experimental arthritis by downregulating KRT7.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, for which effective therapeutic strategies remain limited. AdipoRon, a synthetic adiponectin receptor agonist, has been reported to possess anti-inflammatory properties. In this study, we evaluated the therapeutic potential and underlying mechanisms of AdipoRon in alleviating RA-related synovial inflammatory lesions. In an adjuvant-induced arthritis (AIA) rat model, AdipoRon treatment markedly improved clinical scores and reduced ankle swelling. Histological and micro-CT evaluations demonstrated AdipoRon alleviated synovial inflammatory lesions, cartilage degradation, and bone erosion. In vitro, AdipoRon dose-dependently suppressed TNF-α-induced proliferation, migration, and invasion of fibroblast-like synoviocytes (FLSs). RNA sequencing identified Keratin 7 (Krt7) as a key gene responsive to AdipoRon. Immunofluorescence analysis confirmed upregulated Krt7 expression in RA patient samples. Functional studies demonstrated that Krt7 overexpression promoted synovial inflammation and FLSs migration and invasion, whereas AdipoRon alleviated these pathological processes by downregulating Krt7. Collectively, these results demonstrate that AdipoRon ameliorates synovial inflammation and abnormal FLSs activation by modulating Krt7, therefore supporting its further development as a therapeutic candidate for RA.