[Anti-osteopenic effect of taurine: possible involvement of activated MEK-ERK-Cbfa1 signaling].
Previously we first noted that taurine (TR) has anti-osteopenic effect on low Ca diet-induced osteopenia in rats (1). Employing osteoblastic MC3T3-E1 cells, the mechanism of the anti-osteopenic effect was explored in vitro. TR (1 mM) was found to promote mineralization of extracellular matrices, without affecting alkaline phosphataase activity. Gel shift assay using 32P-labeled OSE2 (osteoblast-specific cis-element 2: the consensus sequence for Cbfa1, refer to 2) indicated that TR (1 mM) increased the nuclear localization of Cbfa1, just as TPH (1-34) (3,4) and bisphosphonates did (5). In addition, TR was found to stimulate ERK phosphorylation. PD98059, a MEK inhibitor, suppressed effects of TR on both Cbfa1 transactivation and ERK activation. The results strongly suggest that TR first activates intracellular MEK-ERK-Cbfa1 signaling system thereby promoting mineralization and finally leading to its bone anabolic action.
Yasutomi
Chigusa
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata 573-0101, Japan.
Nakamuta
Hiromichi
H
Fujita
Takashi
T
Takenaga
Takaaki
T
Koida
Masao
M
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000166:cytology*; D051381:Rats; D013654:Taurine / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors; D013654:Taurine