Cellular Senescence in Human Chondrocytes in Relation to Osteoarthritis.

IntroductionCellular 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 after treatment with the mutagens N-ethyl-N-nitrosourea (ENU) or bleomycin, and then in in cartilage samples from OA patients and control subjects.MethodsCellular 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 and . Cellular senescence in human hip cartilage chondrocytes from OA patients or non-OA controls was similarly evaluated. Apoptosis was measured by the / expression ratio, and by both TUNEL assay and the / ratio.ResultsIn 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. , senescence was observed in bleomycin-treated chondrocytes, but not in ENU-treated cells.ConclusionsOur 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.