CRTAC1 derived from senescent FLSs induces chondrocyte mitochondrial dysfunction <i>via</i> modulating NRF2/SIRT3 axis in osteoarthritis progression.

ABSTRACT: Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1

SUBMITTER: Chen X 

PROVIDER: S-EPMC12648000 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature