GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression.

ABSTRACT: Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression. Here, we elucidate a positive correlation between fibroblast-like synoviocyte senescence and osteoarthritis progression and reveal that GATD3A deficiency induces fibroblast-like synoviocyte senescence. Mechanistically, GATD3A deficiency enhances the binding of Sirt3 to MDH2, leading to deacetylation and decreased activity of MDH2. Reduced MDH2 activity impairs tricarboxylic acid cycle flux, resulting in mitochondrial dysfunction and fibroblast-like synoviocyte senescence. Intra-articular injection of recombinant adeno-associated virus carrying G

SUBMITTER: Shen K 

PROVIDER: S-EPMC11685659 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature