p44/42 MAPK activation is necessary for receptor activator of nuclear factor-kappaB ligand induction by high extracellular calcium.
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-kappaB 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.
Kim
Yong Hee
YH
Department of Pharmacology and Dental Therapeutics, College of Dentistry, Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Kim
Jin Mi
JM
Kim
Si Nae
SN
Kim
Gwan-Shik
GS
Baek
Jeong-Hwa
JH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium