Abstract
The BMP-2/BMP-7 heterodimer (BMP-2/-7) is a potent osteogenic inducer. It is well established that BMP-2/-7 activates mitogen activated protein kinases (MAPKs) in some cells. It is also widely accepted that MAPK signaling cascades play a crucial role in the immediate osteogenic response to BMPs. However, the precise mechanism and role of the MAPK signaling network in osteogenesis is still controversial since there are many kinds of BMP receptors (BMPR) whose signal transduction is very complex and whose signals differ from cell to cell. We investigated whether BMP-2/-7 regulates osteogenic gene expression in human periodontal ligament (HPDL) cells, and how MAPKs might be involved in this process, by treatment of HPDL cells with BMP-2/-7 with or without MAPK inhibitors. We found that the Jun-N-terminal kinase (JNK) is essential for the expression of almost all osteogenic marker genes. Inhibition of extracellular signal-regulated kinase (ERK) using inhibitor had no effect on the expression of early osteogenic marker genes, whereas it significantly down-regulated the expression of late osteogenic marker genes such as Bone sialopotein and Osteocalcin. These results indicate that MAPKs play a crucial role in osteogenesis of HPDL cells.
