Abstract
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.
Data availability
The data sets generated and/or analyzed in the present study can be obtained from the corresponding author upon reasonable request.
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Funding
We also thank the funding support from Qinghai Province basic research project (2024-ZJ-760), Changzhou Sci&Tech Program (CZ20240029), Science and Technology Project of Changzhou Health Commission (ZD202319, ZD202339 and QN202356), China Postdoctoral Science Foundation (2024M750277), and Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project (2022CZBJ059 and 2022CZBJ061).
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Conceptualization: Xiaolong Lin.Data curation: Yaojun Lu.Formal analysis: Xindie Zhou.Funding acquisition: Xindie Zhou.Supervision: Xiaolong Lin.Writing – original draft: Jiliu Huang, Jiapei Yao.Writing – review & editing: Chongrui Li, JingJing Shang.
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Yao, J., Huang, J., Li, C. et al. The TRAF6/SPP1 axis participates in osteoarthritis progression through regulating the catabolism and anabolism of cartilage matrix. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42559-z
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DOI: https://doi.org/10.1038/s41598-026-42559-z
