title: Human chondrocyte senescence and osteoarthritis.
abstract: Although osteoarthritis (OA) is not an inevitable consequence of aging, a strong association exists between age and increasing incidence of OA. We hypothesized that this association is due to in vivo articular cartilage chondrocyte senescence which causes an age-related decline in the ability of the cells to maintain articular cartilage, that is, increasing age increases the risk of OA because chondrocytes lose their ability to replace their extracellular matrix. To test this hypothesis, we measured senescence markers in human articular cartilage chondrocytes from 27 donors ranging in age from one to 87 years. The markers included expression of the senescence-associated enzyme beta-galactosidase, mitotic activity measured by 3H-thymidine incorporation, and telomere length. beta-galactosidase expression increased with age (r=0.84, p=0.0001) while mitotic activity and mean telomere length declined (r=-0.774, p=0.001 and r=-0.71, p=0.0004, respectively). Decreasing telomere length was strongly correlated with increasing expression of beta-galactosidase and decreasing mitotic activity. These findings help explain the previously reported age related declines in chondrocyte synthetic activity and responsiveness to anabolic growth factors and indicate that in vivo articular cartilage chondrocyte senescence is responsible, at least in part, for the age related increased incidence of OA. The data also imply that people vary in their risk of developing OA because of differences in onset of chondrocyte senescence; and, the success of chondrocyte transplantation procedures performed to restore damaged articular surfaces in older patients could be limited by the inability of older chondrocytes to form new cartilage. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells.
authors.affiliation: University of Iowa Department of Orthopaedic Surgery, Iowa City, IA 52242, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Buckwalter
mesh_terms: D000375:Aging / Q000235:genetics*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008938:Mitosis; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D012307:Risk Factors; D016615:Telomere / Q000648:ultrastructure; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase