Opposing role of mitogen-activated protein kinase subtypes, Erk-1/2 and p38, in the regulation of chondrogenesis of mesenchymes

The present studies were performed to determine subtype-specific roles of m itogen-activated protein kinase in chondrogenesis, Erk-1/2 activities, down stream of protein kinase C, decreased as chondrogenesis proceeded, whereas p38 activities, independent of protein kinase C, continuously increased dur ing chondrogenesis. Inhibition of Erk-1/2 with PD98059 enhanced chondrogene sis up to 1.7-fold, whereas inhibition of p38 with SB203580 reduced it to a bout 30% of the control level. Inhibition of Erk-1/2 or p38 did not affect precartilage condensation. However, cartilage nodule formation was signific antly blocked by the inhibition of p38, whereas Erk-1/2 inhibition did not affect it. Modulation of chondrogenesis by the inhibition of Erk-1/2 and p3 8 was accompanied by altered expression of adhesion molecules in an opposit e way. Expression of N-cadherin was reduced as chondrogenesis proceeded. In hibition of p38 caused sustained expression of N-cadherin, whereas Erk-1/2 inhibition accelerated the reduction of N-cadherin expression. Expression o f integrin alpha 5 beta 1 and fibronectin were found to transiently increas e during chondrogenesis. Inhibition of p38 caused continuous increase of ex pression of these molecules, whereas Erk-1/2 inhibition accelerated the dec rease of expression of these molecules at a later period of chondrogenesis. Because temporal expression of these adhesion molecules regulates chondrog enesis, the above results indicate that Erk-1/2 and p38 conversely regulate chondrogenesis at post-precartilage condensation stages by modulating expr ession of adhesion molecules.