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 <i>in vitro</i> after treatment with the mutagens N-ethyl-N-nitrosourea (ENU) or bleomycin, and then in <i>vivo</i> 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 <i>p16</i> and <i>p21</i>. Cellular senescence in human hip cartilage chondrocytes from OA patients or non-OA controls was similarly evaluated. Apoptosis <i>in vitro</i> was measured by the <i>Bcl-2</i>/<i>Bax</i> expression ratio, and <i>in vivo</i> by both TUNEL assay and the <i>Bcl-2</i>/<i>Bax</i> 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. <i>In vitro</i>, 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.