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

• Published in: Biochemical and biophysical research communications Vol. 304; no. 4; pp. 729 - 735
• Main Authors: Kim, Yong Hee, Kim, Jin Mi, Kim, Si Nae, Kim, Gwan-Shik, Baek, Jeong-Hwa
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.05.2003
• Subjects: Calcium-sensing receptor; Extracellular calcium; Osteoblast; p44/42 MAPK; RANKL; Extracellular calcium; Osteoblast; RANKL; Calcium-sensing receptor; p44/42 MAPK
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(03)00661-2

Although extracellular calcium (Ca 2+ o) has been suggested to modulate bone remodeling, the exact mechanism is unclear. This study was performed to explore the signaling pathways of high Ca 2+ o that are responsible for controlling the expression of receptor activator of NF-κB ligand (RANKL) in mouse osteoblastic cells. As previously reported, high Ca 2+ o increased RANKL expression. However, the G protein-coupled Ca 2+ 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 Ca 2+ o. In contrast, the inhibition of p44/42 MAPK pathway reduced the RANKL expression induced by high Ca 2+ o. Moreover, high Ca 2+ o activated p44/42 MAPK and MEK1/2. These results suggest that RANKL induction by high Ca 2+ 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 Ca 2+ o-induced RANKL expression in mouse osteoblastic cells.