Involvement of ERK in BMP-2 induced osteoblastic differentiation of mesenchymal progenitor cell line C3H10T1/2

The signaling mechanisms responsible for bone morphogenetic protein (BMP) i nduced osteoblast differentiation remains poorly understood. Previous resea rch demonstrated that Smad proteins are the substrates and the mediators of BMP bound serine/threonine receptor kinase. In the present study, we exami ned the possible involvement of extracellular signal-regulated kinase (Erk) in the BMP induced osteoblast differentiation of mesenchymal progenitor ce ll C3H10T1/2. Our results indicate that BMP-2 inducement increased MAP kina se activity in mesenchymal progenitor cell line C3H10T1/2. Contrary to prev ious reports, this increased MAP kinase activity showed a latent but sustai ned pattern. Elevation of Erk1 and Erk2 protein levels was observed simulta neously. RT-PCR results demonstrated that the elevation of Erk protein leve l in BMP-2 induced cells was from the upregulation of mRNA expression. Furt hermore, upregulated Erk proteins present enhanced phosphorylation. By usin g a dominant-negative Erk2 cell line, we demonstrated that nonfunctional Er k2 partially eliminated BMP-2 induced cell proliferation and ALP activity i n the C3H10T1/2 cell. These results indicate that Erk is involved in BMP-2 induced osteoblast differentiation. The results also demonstrate that a lat ent and sustained signaling pattern exists in BMP induced signaling cascade . (C) 2000 Academic Press.