Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells

Extracellular signal-regulated kinases (Erks), members of the mitogen-activ ated protein kinase superfamily, play an important role in cell proliferati on and differentiation. In this study we employed a dominant negative appro ach to determine the role of Erks in the regulation of human osteoblastic c ell function. Human osteoblastic cells were transduced with a pseudotyped r etrovirus encoding either a mutated Erk1 protein with a dominant negative a ction against both Erk1 and Erk2 (Erk1DN cells) or the LacZ protein (LacZ c ells) as a control. Both basal and growth factor-stimulated MAPK activity a nd cell proliferation were inhibited in Erk1DN cells. Expression of Erk1DN protein suppressed both osteoblast differentiation and matrix mineralizatio n by decreasing alkaline phosphatase activity and the deposition of bone ma trix proteins. Cell adhesion to collagen, osteopontin, and vitronectin was decreased in Erk1DN cells as compared with LacZ cells. Cell spreading and m igration on these matrices were also inhibited. In Erk1DN cells, expression of alpha beta (1), alpha (v)beta (3) and alpha (v)beta (5) integrins on th e surface was decreased. Metabolic labeling indicated that the synthesis of these integrins was inhibited in Erk1DN cells. These data suggest that Erk s are not only essential for the growth and differentiation of osteoblasts but also are important for osteoblast adhesion, spreading, migration, and i ntegrin expression.