Telomere erosion and senescence in human articular cartilage chondrocytes

Abstract

Aging and the degeneration of articular cartilage in osteoarthritis are distinct processes, but a strong association exists between age and the incidence and prevalence of osteoarthritis. We hypothesized that this association is due to in vivo replicative senescence, which causes age-related declines in the ability of chondrocytes to maintain articular cartilage. For this hypothesis to be tested, senescence-associated markers were measured in human articular chondrocytes from donors ranging in age from 1 to 87 years. These measures included in situ staining for senescence-associated beta-galactosidase activity, (3)H-thymidine incorporation assays for mitotic activity, and Southern blots for telomere length determinations. We found that senescence-associated beta-galactosidase activity increased with age, whereas both mitotic activity and mean telomere length declined. These findings indicate that chondrocyte replicative senescence occurs in vivo and support the hypothesis that the association between osteoarthritis and aging is due in part to replicative senescence. The data also imply that transplantation procedures performed to restore damaged articular surfaces could be limited by the inability of older chondrocytes to form new cartilage after transplantation.