Inactivation of p38 kinase delays the onset of senescence in rabbit articular chondrocytes

Abstract

Replicative senescence limits cellular proliferation in vivo and in vitro. Recently, other groups and we reported that p38 kinase plays a key role on the onset of senescence. In this study, we demonstrated that replicative senescence can be delayed in rabbit chondrocytes in vitro by that p38 kinase inactivation. We found that the activity of p38 kinase is elevated in senescent chondrocytes as compared to pre-senescent counterparts. To examine the role of p38 kinase on the onset of senescence, we inactivated the kinase pharmacologically or genetically using either a chemical inhibitor, SB203580, or dominant negative mutant forms of MKK6 and p38 (MKK6A and p38dn, respectively). We show that the inactivation of p38 kinase leads to the stimulation of proliferation, the extension of life span, and a delay in the onset of senescence, thus implying that p38 kinase limits the life span of rabbit articular chondrocytes in vitro.