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A study on expression and function of bone morphogenetic protein during maxillofacial development

颌面部发育过程中骨形态发生蛋白的表达及功能研究

基本信息

批准号：
06671993
负责人：
IWAKI Hiroshi
金额：
$ 0.58万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671993/
关键词：
BMP BMP receptor TGF-beta activin 骨形成タンパク質(BMP)TGF-βスーパーファミリー

项目摘要

Bone Morphogenetic Protein (BMP), which belongs to the transforming growth factor-beta (TGF-beta) superfamily, was originally identified in the extract from bone by its capacity to induce ectopic bone formation. Recent studies have revealed that BMPs are involved in maxillofacial development. In order to investigate the precise molecular mechanism of BMPs in maxillofacial development, we performed the following studies.Dental pulp has a potential to induce ectopic bone formation. We thought that bone morphogenetic proteins (BMPs) are involved in the osteoinductive activity of dental pulp. In order to prove this assumption, we constructed a cDNA library from primary culture cells of human dental pulp (HDP cells). Three distinct cDNA clones encoding human BMP-2, -4, -6 were isolated. To elucidate the receptor system of BMP,we performed molecular clonning of rat BMP receptor. PCR-based analysis revealed that mRNA for BMP receptors were expressed in the BMP-induced bone forming tissues throughout the stages tested and that mRNA for activin receptor was also expressed. These results suggest that these receptors play imporatant roles for the ectopic bone formation induced by BMP.In addition, expression of mRNAs for TGB-beta receptors and activin receptors was also detected in the BMP-implanted tissues, which suggested the possible involvement of TGF-betas and activins as ligands in the ectopic bone formation.

骨形态发生蛋白（BMP）属于转化生长因子-β（TGF-β）超家族，最初通过其诱导异位骨形成的能力在骨提取物中鉴定。近年来的研究表明骨形成蛋白参与颌面部发育。为了探讨骨形成蛋白在颌面部发育中的确切分子机制，我们进行了以下研究：牙髓具有诱导异位骨形成的潜能。我们认为骨形态发生蛋白（BMP）参与牙髓的骨诱导活性。为了证明这一假设，我们构建了人牙髓原代培养细胞（HDP细胞）的cDNA文库。分离了编码人BMP-2、-4、-6的3个不同的cDNA克隆。为了阐明BMP的受体系统，我们对大鼠BMP受体进行了分子克隆。基于PCR的分析显示，BMP受体的mRNA在BMP诱导的骨形成组织中在整个测试阶段中表达，并且激活素受体的mRNA也表达。这些结果表明，这些受体在BMP诱导的异位骨形成中起重要作用。此外，在BMP植入组织中还检测到TGF-β受体和激活素受体的mRNA表达，这提示TGF-β和激活素可能作为配体参与异位骨形成。