biostudies-literatureUnknown16(1)Zhao JMetabolic alterations in chondrocytes play a crucial role in the progression of temporomandibular joint osteoarthritis (TMJOA). However, the precise molecular mechanisms underlying these changes remain poorly understood. In this study, we identify ubiquitin-specific protease 32 (USP32) as a key regulator of TMJOA progression through its interaction with pyruvate kinase M2 (PKM2), a vital enzyme in glycolysis. Our results demonstrate that USP32 is significantly upregulated in TMJOA cartilage and inflammatory chondrocytes. USP32 stabilizes PKM2 by removing K48- and K11-linked ubiquitin chains, thereby preventing its proteasomal degradation. This stabilization promotes the accumulation of PKM2, leading to enhanced glycolysis, increased lactate production, and mitochondrial dysfunction, all ofCell death & disease781https://www.ebi.ac.uk/biostudies/studies/S-EPMC12583448biostudies-literatureUSP32 promotes temporomandibular joint osteoarthritis by modulating PKM2 stability and glycolytic metabolism in chondrocytes.PMC12583448Wang MLiu ZFeng ZDu TQi KLi RZhao JLi MfalseUSP32 promotes temporomandibular joint osteoarthritis by modulating PKM2 stability and glycolytic metabolism in chondrocytes.Metabolic alterations in chondrocytes play a crucial role in the progression of temporomandibular joint osteoarthritis (TMJOA). However, the precise molecular mechanisms underlying these changes remain poorly understood. In this study, we identify ubiquitin-specific protease 32 (USP32) as a key regulator of TMJOA progression through its interaction with pyruvate kinase M2 (PKM2), a vital enzyme in glycolysis. Our results demonstrate that USP32 is significantly upregulated in TMJOA cartilage and inflammatory chondrocytes. USP32 stabilizes PKM2 by removing K48- and K11-linked ubiquitin chains, thereby preventing its proteasomal degradation. This stabilization promotes the accumulation of PKM2, leading to enhanced glycolysis, increased lactate production, and mitochondrial dysfunction, all of2025-01-01T00:00:00Z2025 Nov2026-06-05T11:49:03.299Z2026-05-16T03:13:22.131ZS-EPMC125834484118422810.1038/s41419-025-08053-6