Modulation of cellular differentiation by N-methyl-D-aspartate receptors in osteoblasts.
N-methyl-D-aspartate (NMDA) receptors for the central neurotransmitter l-glutamate (Glu) have been shown to be present in both osteoblasts and osteoclasts. Sustained exposure to the NMDA channel antagonist dizocilpine (MK-801) significantly prevented increases in both alkaline phosphatase activity and Ca2+ accumulation in a concentration-dependent manner in osteoblasts cultured for 7-28 days in vitro (DIV), without significantly affecting cell survivability. Osteocalcin expression was markedly reduced in the presence of MK-801 in osteoblasts cultured for 28 DIV. Both an NMDA domain antagonist and a glycine domain antagonist similarly prevented Ca2+ accumulation in osteoblasts exposed for 28 consecutive DIV. MK-801 was effective in significantly inhibiting Ca2+ accumulation determined at 28 DIV in osteoblasts exposed before 7 DIV but was ineffective in cells exposed after 11-21 DIV. Sustained exposure to MK-801 significantly inhibited DNA binding activity and expression of core binding factor alpha-1 (CBFA1) in osteoblasts exposed after 7 DIV up to 28 DIV, but not in those exposed before 7 DIV. These results suggest that heteromeric NMDA receptor channels may be functionally expressed to regulate mechanisms underlying cellular differentiation rather than proliferation and/or maturation through modulation of expression of CBFA1 in cultured rat calvarial osteoblasts.
Hinoi
Eiichi
E
Laboratory of Molecular Pharmacology, Kanazawa University Graduate School of Natural Science and Technology, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
Fujimori
Sayumi
S
Yoneda
Yukio
Y
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008954:Models, Biological; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D009363:Neoplasm Proteins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D015675:Osteocalcin; D016291:Dizocilpine Maleate