Cellular Senescence in Human Chondrocytes in Relation to Osteoarthritis

Introduction: Cellular senescence, i.e., a state of permanent cessation of cell division, is a hallmark of aging and has been associated with age-related diseases, most notably osteoarthritis (OA). Here we assessed senescence in chondrocytes, first in vitro after treatment with the mutagens N-ethyl-N-nitrosourea (ENU) or bleomycin, and then in vivo in cartilage samples from OA patients and control subjects. Methods: Cellular senescence in cultured chondrocytes treated with mutagens was assessed by senescence-associated β-galactosidase (SA-β-gal) staining and by evaluating the expression levels of p16 and p21. Cellular senescence in human hip cartilage chondrocytes from OA patients or non-OA controls was similarly evaluated. Apoptosis in vitro was measured by the Bcl-2/Bax expression ratio, and in vivo by both TUNEL assay and the Bcl-2/Bax ratio. Results: In human articular cartilage, senescent cells were found to be significantly elevated in OA lesions of patients as compared with normal cartilage of non-OA control subjects. In vitro, senescence was observed in bleomycin-treated chondrocytes, but not in ENU-treated cells. Conclusions: Our findings demonstrate that cellular senescence is associated with the pathogenesis of OA, with DNA damage and mutations as potential contributing factors in OA-associated senescence.