p38 mitogen-activated protein kinase affects transforming growth factor-β/Smad signaling in human dental pulp cells

Transforming Growth Factor-beta (TGF-beta) plays an essential role in differentiation of dental pulp cells into odontoblasts during reparative dentine formation. However, the mechanism by which TGF-beta stimulates dental repair remains rather obscure. Human dental pulp cells were used as an in vitro model in the present work. We showed that TGF-beta signaled through mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38, along with Smad pathway. Distinct pathways exerted different time response. SB203580, a specific p38 MAPK inhibitor, reduced phosphorylation of Smad3, while it slightly enhanced phosphorylation of Smad2. Increased phosphorylation of ERK1/2 and p38 confirmed that SB203580 did not block activation of TGF-beta receptors. In addition, the inhibition of ERK1/2 activity with MEK1/2 inhibitor U0126 increased TGF-beta mediated phosphorylation of Smad3. Our results suggest that p38 affects the phosphorylation of Smad2 and Smad3 differentially during TGF-beta signaling in human dental pulp cells and ERK1/2 might be involved in the process.