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，最初在骨提取液中发现具有诱导异位成骨的能力。最近的研究表明，BMP参与了颌面部的发育。为了研究BMPs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力。我们认为骨形态发生蛋白(BMPs)参与了牙髓的成骨活性。为了验证这一假设，我们从人牙髓原代培养细胞(HDP细胞)中构建了一个cDNA文库。分离到3个不同的编码人骨形成蛋白-2、-4、-6的基因克隆。为了阐明BMP受体系统，我们进行了大鼠BMP受体的分子克隆。以聚合酶链式反应为基础的分析表明，BMP受体的mRNA在BMP诱导的骨形成组织中表达，激活素受体的mRNA也表达。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植入的组织中还检测到TGB-β受体和激活素受体的mRNAs的表达，提示转化生长因子-β和激活素可能作为配体参与了异位骨的形成。

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.