Vitamin D(3) enhances the expression of I-mfa, an inhibitor of the MyoD family, in osteoblasts.
I-mfa (inhibitor of the MyoD family) is a transcription modulator that binds to and suppresses the transcriptional activity of MyoD family members. I-mfa transcripts are expressed in sclerotome, suggesting a role of I-mfa in skeletogenesis. The aim of this study was to examine the expression and regulation of I-mfa in osteoblasts. We found that I-mfa is expressed at a low level in an osteoblast-like cell line, MC3T3E1, and a pluripotent differentiation modulator, 1,25-dihydroxyvitamin D(3), specifically enhanced I-mfa mRNA expression. This effect was completely blocked by the presence of an RNA polymerase inhibitor, but not by a protein synthesis inhibitor, suggesting that 1,25-dihydroxyvitamin D(3) upregulates transcription of the I-mfa gene without requirement for new protein synthesis. Western blot analysis indicated that 1,25-dihydroxyvitamin D(3) increased the I-mfa protein levels severalfold in MC3T3E1 cells. I-mfa expression was also observed in primary mouse calvaria cells and ROS17/2.8 cells and 1,25-dihydroxyvitamin D(3) enhanced I-mfa expression in these cells. These data indicate that I-mfa is a novel transcriptional regulator gene expressed in osteoblasts and that its level is under the control of 1,25-dihydroxyvitamin D(3).
Tsuji
K
K
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Kraut
N
N
Groudine
M
M
Noda
M
M
D000818:Animals; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D017570:MyoD Protein / Q000037:antagonists & inhibitors; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012886:Skull / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D004791:Enzyme Inhibitors; C491077:Mdfi protein, mouse; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D002762:Cholecalciferol; D004004:Dichlororibofuranosylbenzimidazole; D003513:Cycloheximide