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

骨形态发生蛋白（BMP）属于转化生长因子- β (tgf - β)超家族，最初在骨提取物中发现其诱导异位骨形成的能力。最近的研究表明bmp参与了颌面发育。为了研究BMPs在颌面发育中的确切分子机制，我们进行了以下研究。牙髓有可能诱发异位骨形成。我们认为骨形态发生蛋白（BMPs）参与了牙髓的成骨诱导活性。为了证明这一假设，我们从人牙髓原代培养细胞（HDP细胞）中构建了cDNA文库。分离到3个不同的cDNA克隆，分别编码人BMP-2、-4、-6。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诱导的成骨组织中BMP受体mRNA在整个测试阶段均有表达，激活素受体mRNA也有表达。这些结果提示这些受体在BMP诱导的异位骨形成中起重要作用。此外，在bmp植入组织中也检测到tgb - β受体和激活素受体mrna的表达，这表明tgf - β和激活素可能作为配体参与异位骨形成。

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.