Artemotil Attenuates Fibrosis-Associated Chondrocyte Remodelling in Osteoarthritis in Association With STC1-Related TGF-β/SMAD2/3 Signalling.

Cartilage fibrosis contributes to extracellular matrix remodelling and structural deterioration during osteoarthritis (OA) progression; however, the molecular regulators involved in this process remain incompletely understood. Stanniocalcin-1 (STC1) has been implicated in tissue remodelling and fibrosis-associated signalling, but its role in chondrocyte fibrotic phenotype transition remains unclear. In this study, primary mouse chondrocytes stimulated with interleukin-1β (IL-1β), a destabilization of the medial meniscus (DMM) mouse model, and human OA cartilage samples were used to investigate the involvement of STC1 in OA-associated fibrotic remodelling. Quantitative proteomic profiling identified STC1 as a differentially regulated candidate associated with inflammatory and fibrotic responses. STC1 expression was elevated under OA-related conditions and was accompanied by increased SMAD2/3 phosphorylation. In SW1353 chondrosarcoma-derived chondrocytic cells, STC1 overexpression enhanced fibrosis-associated phenotypic changes, including increased COL1A1, ADAMTS5, and MMP-3 expression, reduced COL2A1 expression, and increased SMAD2/3 phosphorylation. Pharmacological modulation experiments further supported an association between STC1 and TGF-β/SMAD2/3 signalling activity. Artemotil attenuated fibrotic and catabolic responses in IL-1β-stimulated chondrocytes, reduced cartilage degeneration in DMM-induced OA, and was associated with reduced STC1 expression and reduced SMAD2/3 phosphorylation. Restoration of STC1 expression partially attenuated the effects of Artemotil on fibrosis-related markers and signalling alterations. These findings support a functional association between STC1, TGF-β-responsive SMAD2/3 signalling, and fibrosis-associated chondrocyte remodelling in OA and identify this signalling relationship as responsive to Artemotil intervention.