Targeting Caspase-1 in osteoarthritis: multi-omics insights into the effects of VX-765 on human chondrocyte function and phenotype.

ABSTRACT:

Background

Osteoarthritis (OA) progression involves chronic inflammation, chondrocyte senescence, and extracellular matrix (ECM) degradation affecting all synovial joint tissues. To date, no regenerative OA drugs have been approved. Caspase-1, a core effector of the inflammasome, may contribute to OA via both canonical inflammatory and non-canonical functions, but its therapeutic value remains unclear.

Methods

We combined transcriptomic, proteomic, functional, and Mendelian randomization (MR) approaches. Using GSE168505 data, we analyzed CASP1, CARD gene family members (CARD16/17/18/8), and OA-related genes in OA- versus non-OA chondrocytes. We established an in vitro OA model by treating human chondrocytes with TNF-α ± VX-765 and assessed Caspase-1 activity, cell met

SUBMITTER: Mei J 

PROVIDER: S-EPMC12532135 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature