UGDH Lactylation Aggravates Osteoarthritis by Suppressing Glycosaminoglycan Synthesis and Orchestrating Nucleocytoplasmic Transport to Activate MAPK Signaling.

ABSTRACT: Osteoarthritis (OA) progression is closely related to dysregulated glycolysis. As the primary metabolite of glycolysis, lactate plays a detrimental role in OA. However, how lactate exacerbates OA process remains unclear. Here, this study revealed that lactate levels are elevated in the synovial fluid of OA patients and IL-1β-treated human primary chondrocytes, promoting protein pan-lactylation. Functionally, hyper-lactylation exacerbates chondrocytes extracellular matrix (ECM) degradation and cell apoptosis in vitro and in vivo. Moreover, UDP-glucose dehydrogenase (UGDH) is proven to be the key lactylated protein in lactate-treated chondrocytes, which undergoes lactylation at lysine 6 (K6). Lactylated UGDH repressed its enzymatic activity, reducing glycosaminoglycan synthesis and disregula

SUBMITTER: Lan W 

PROVIDER: S-EPMC12120796 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature