Objective. Articular chondrocyte senescence is responsible, at least in part, for the increased incidence of osteoarthritis (OA) with increased age. Recently, it was suggested that caveolin 1, a 21-24-kd membrane protein, participates in premature cellular senescence. Caveolin 1 is the principal structural component of caveolae, vesicular invaginations of the plasma membrane. This study was undertaken to investigate whether the catabolic factors oxidative stress and interleukin-1␤ (IL-1␤) induce features of premature senescence of articular chondrocytes through up-regulation of caveolin 1 expression.Methods. Caveolin 1 expression was investigated in human OA cartilage by real-time polymerase chain reaction and in rat OA cartilage by immunohistologic analysis. We studied whether IL-1␤ and H 2 O 2 induce caveolin 1 expression in OA chondrocytes and analyzed the relationship between cellular senescent phenotypes and caveolin 1 expression in human chondrocytes.Results. In human and rat OA articular cartilage, caveolin 1 positivity was associated with cartilage degeneration. Both IL-1␤ and H 2 O 2 up-regulated caveolin 1 messenger RNA and protein levels, and both treatments induced marked expression of senescent phenotypes: altered cellular morphology, cell growth arrest, telomere erosion, and specific senescence-associated ␤-galactosidase activity. Caveolin 1 overexpression induced p38 MAPK activation and impaired the ability of chondrocytes to produce type II collagen and aggrecan. Articular cartilage stability depends on the biosynthetic activities of chondrocytes, which counteract normal degradation of matrix macromolecules. Aging and the degeneration of articular cartilage in osteoarthritis (OA) are distinct processes; however, the incidence and prevalence of synovial joint degeneration increase dramatically in middle age (1) and the risk of posttraumatic OA following intraarticular fracture of

No abstract

No abstract

No abstract