NAT10-mediated ac4C modification of KDM1B drives osteoarthritis progression through epigenetic suppression of SOX9.

ABSTRACT: Histone methylation acts as a crucial regulator of diverse pathophysiological processes in humans. However, the involvement of histone methylation modification enzymes in osteoarthritis (OA) remains poorly characterized. Here, we delineated lysine demethylase 1B (KDM1B) as a nodal epigenetic effector driving OA pathobiology through an integrated strategy that combined data mining, bioinformatics analysis, and experimental validation. Gain-of-function studies revealed that chondrocyte - specific KDM1B overexpression amplified IL-1β-induced chondrocyte injury primarily through the inhibition of SRY-box transcription factor 9 (SOX9). Conversely, KDM1B knockdown inhibited IL-1β-induced chondrocyte damage in vitro and significantly alleviated OA progression in vivo by upregulating SOX9. Mechani

SUBMITTER: Chen S 

PROVIDER: S-EPMC12647510 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature