Osteoarthritis (OA) is an age-related degenerative disease without disease-modifying therapy. The lack of aging-induced osteoarthritis models makes the discovery of therapeutic drugs more challenging. The deficiency of ZMPSTE24 could induce Hutchinson–Gilford progeria syndrome (HGPS), a genetic disorder of rapid aging. However, the relationship between HGPS and OA remains unclear. Our results found that the expression ofZmpste24was decreased in the articular cartilage during the aging process.Zmpste24 knockoutmice,Prx1-Cre; Zmpste24fl/flmice andCol2-CreERT2; Zmpste24fl/flmice displayed OA phenotype. Loss ofZmpste24in articular cartilage could exacerbate the occurrence and development of osteoarthritis. Transcriptome sequencing revealed that deletion ofZmpste24or accumulation of progerin affects chondrocyte metabolism, inhibits cell proliferation and promotes cell senescence. Using this animal model, we elucidate the upregulation of H3K27me3 during chondrocyte senescence and discover the molecular mechanism by which lamin A mutant stabilizes EZH2 expression. The construction of aging-induced osteoarthritis models and the elucidation of the signaling pathways and molecular mechanisms of articular chondrocyte senescence would benefit the discovery and development of new drugs for OA.