The TRAF6/SPP1 axis participates in osteoarthritis progression through regulating the catabolism and anabolism of cartilage matrix.

Osteoarthritis (OA), a widespread form of degenerative joint disorder, is characterized by the gradual deterioration of articular cartilage.Serving as a versatile signaling mediator, tumor necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in regulating cartilage matrix metabolism by controlling inflammatory mediators. This investigation examines the TRAF6/SPP1 pathway’s dual role in cartilage matrix remodeling during OA pathogenesis. Through integrated approaches including in vitro chondrocyte models, gene manipulation techniques, molecular assays (qRT-PCR, Western blot), and preclinical animal studies, we establish that TRAF6-mediated upregulation of secreted phosphoprotein 1 (SPP1) drives both matrix degradation and repair mechanisms in OA joints. Experimental evidence further demonstrates SPP1’s capacity to modulate chondrocyte-specific genetic markers, thereby influencing tissue degeneration and regenerative processes. These results elucidate the central regulatory mechanism of the TRAF6/SPP1 signaling cascade in OA pathophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-42559-z.