p44/42 MAPK is necessary for receptor activator of nuclear factor-kB ligand induction by extracellular high calcium

Abstract

Although extracellular calcium (Ca2+o) has been suggested to modulate bone remodeling, the exact mechanism is unclear. This study was performed to explore the signaling pathways of high Ca2+o that are responsible for controlling the expression of receptor activator of NF-κB ligand (RANKL) in mouse osteoblastic cells. As previously reported, high Ca2+o increased RANKL expression. However, the G protein-coupled Ca2+o-sensing receptor (CaSR) was not detected in the primary cultured mouse osteoblastic cell. The inhibition of the pertussis-sensitive G protein, phospholipase C, protein kinase C, intracellular calcium mobilization, p38 MAPK, or phosphoinositide 3-kinase did not block RANKL induction caused by high Ca2+o. In contrast, the inhibition of p44/42 MAPK pathway reduced the RANKL expression induced by high Ca2+o. Moreover, high Ca2+o activated p44/42 MAPK and MEK1/2. These results suggest that RANKL induction by high Ca2+o might not be mediated by CaSR and its putative downstream signaling pathways, but the pathway employing p44/42 MAPK is involved in the high Ca2+o-induced RANKL expression in mouse osteoblastic cells.