Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo
Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo
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DOI：
10.1002/jcb.20154
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Maeda, Y;Tsuji, K;Noda, M
骨的形成受一系列转录因子的控制。IDs是一种抑制螺旋-环-螺旋(HLH)转录因子，其在成骨细胞中的表达受骨形态发生蛋白和维生素D等促钙剂的调控，但其在体内成骨过程中的作用尚不清楚。因此，我们研究了Id1和Id3在体内骨代谢调节中的作用。以野生型和Id1/Id3杂合基因敲除小鼠为研究对象，通过X线照片分析颅骨骨缝内的骨形成，用四甲基偶氮唑盐比色法和茜素红染色分析原代成骨细胞的增殖和矿化活性，用BMP注射入颅骨进行体内原位成骨和显微CT分析。Id1/Id3杂合基因敲除小鼠颅骨缝宽度减少50%以上。对突变小鼠缺陷机制的细胞基础分析显示，来自Id1/ID3杂合敲除小鼠的成骨细胞的增殖和矿化受到抑制。此外，Id1/Id3杂合基因敲除小鼠在体内抑制了BMP诱导的骨形成。这些结果表明，Id1和Id3是促进体内骨形成的积极因素。(C)2004年Wiley-Liss公司
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 knock out 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. (C) 2004 Wiley-Liss, Inc.