β-galactosidase-targeted senolytic prodrug ameliorates preclinical models of post-traumatic osteoarthritis.

ABSTRACT:

Background

Cellular senescence is involved in the pathogenesis of osteoarthritis (OA). This study aimed to identify prodrug SSK1 as a senolytic strategy for alleviating OA.

Methods

An oxidative stress-induced cellular senescence model was established to evaluate cell viability, replication, and genotoxicity after SSK1 treatment. Human OA chondrocytes and explants were collected to evaluate the therapeutic effect of prodrug SSK1 in vitro. In vivo evaluation was performed in young and aged male murine models. SSK1 (intra-articular injection every 3 days) was administrated 2 weeks after anterior cruciate ligament transection (ACLT) surgery. Animals were sacrificed 8 weeks after surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related

SUBMITTER: Li Q 

PROVIDER: S-EPMC12637248 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature