Chondrocyte senescence, joint loading and osteoarthritis.

摘要: cellular level is not completely understood, but both aging and loading-induced stresses have been shown to undermine cell functions related the maintenance restoration of cartilage matrix. Based on precedents set by studies other age-related degenerative diseases, we focused our laboratory work senescence as cause age-dependent decline in chondrocytes impact excessive mechanical promoting senescence. We hypothesized that senescent accumulate with age articular propose stress plays a role this process oxidative damage ultimately causes them senesce. To test hypothesis, measured markers (beta-galactosidase expression, mitotic activity, telomere length) human chondrocytes, determined effects chronic exposure chondrocyte growth In addition, abnormally high levels shear release oxidants explants. found accumulated cartilage. vitro showed caused repeated peroxide, or under superphysiologic oxygen tension populations senesce prematurely, before extensive erosion occurred. Mechanical applied explants considerably increased production oxidants. These observations support hypothesis accounts for function indicate mechanically induced process. This suggests new efforts prevent development progression osteoarthritis should include strategies slow replace cells.