Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo.
Bone formation is under the control of a set of transcription factors. Ids are inhibitory helix-loop-helix (HLH) transcription factors and expression of Id genes in osteoblasts is under the control of calciotropic agents such as BMP and vitamin D. However, the function of Ids during bone formation in vivo has not yet been elucidated. We, therefore, examined the role of Id1 and Id3 in the regulation of bone metabolism in vivo. Using wild type and Id1/Id3 heterozygous knockout mice, we analyzed calvarial bone formation in the suture by X-ray picture, proliferation, and mineralization activities of primary calvarial osteoblasts by MTT assay and alizarin red staining and onthotopic in vivo bone formation by BMP injection onto calvaria and micro CT analysis. The width of calvarial sutures was reduced by more than 50% in Id1/Id3 heterozygous knock out mice. Analyses on the cellular basis for the mechanism underlying the defects in the mutant mice revealed suppression of proliferation and mineralization in osteoblasts derived from Id1/Id3 heterozygous knock out mice. Furthermore, Id1/Id3 heterozygous knock out mice suppressed BMP-induced bone formation in vivo. These results indicated that Id1 and Id3 are positive factors to promote bone formation in vivo.
Maeda
Yukiko
Y
Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
Tsuji
Kunikazu
K
Nifuji
Akira
A
Noda
Masaki
M
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C067679:Idb3 protein, mouse; D012313:RNA