Biological and clinical study on regulation of gene expression in osteoblast and its osteogenesis

我们研究了PDGF对人成骨细胞生长的刺激作用。PDGF促进这些细胞的增殖，其机制是通过PDGF受体的酪氨酸激酶活性和细胞蛋白的磷酸化来实现的。我们还在研究PDGF对这些细胞的基因表达的诱导作用。生物学的骨形成系统是研究成骨细胞在骨重建中的作用所必需的。将人骨来源的成骨细胞注射到扩散腔内，然后移植到裸鼠体内。6~8周后，接触膜滤器的细胞层内形成钙化小体。在超微结构上，我们发现这个钙化体具有与活体骨形成相似的过程。众所周知，骨髓组织中含有能够向成骨方向分化的细胞。在该培养体系中可形成包埋成骨细胞和骨细胞的矿化结节。通过电子显微镜研究，这种矿化被认为是伴随着基质小泡一起开始的，并沿着胶原纤维进行。以全身性骨硬化为特征的骨化症，已经注意到破骨细胞的分化和骨的重建。我们研究了一位骨化症患者的下颌骨结构。骨髓腔几乎被硬化骨占据，片层非常不规则。皮质骨中未见正常骨改建的迹象，不仅成骨细胞与软骨细胞有关，而且与骨骼生长有关。利用终末分化的软骨细胞，我们研究了维甲酸如何刺激其增殖和诱导去分化。从我们的实验中，我们认为蛋白激酶C的活性介导了维甲酸对该软骨细胞的作用。

We investigated the effect of PDGF on growth stimulation in human osteoblastic cells. PDGF stimulated the proliferation of these cells and this mechanism was mediated by tyrosin kinase activity of the PDGFrecepter followed by phosphorylation of cellular proteins. We are also studying the induction of gene expression by PDGF in these cells.Biological bone formation system is necessary for studying on a role of osteoblast during bone remodeling. Osteoblasts derived from human bone were injected in diffusion chamber and implanted intraperitoneally into nude mouse. After 6-8 weeks, calcified body was formed in the cell layer touched membrane filter. Ultrastructually, we showed this calcified body had the similar process to bone formation in vivo.Bone marrow tissue is known to contain the cells which can differentiate to the osteogenic direction. On this culture system, mineralized nodules which embedded osteoblasts and osteocytes were formed. By electron-microscopic study, this mineralization was considered to be initiated in association with the matrix vesicles and to progress along the collagen fibrils.Osteopetrosis, characterized by a systemic osteosclerosis, has been given attention to the osteoclast differentiation and bone remodering. We studied the structures of the mandible of a man who had osteopetrosis. The bone marrow cavity was almost occupied by sclerotic bone with very irregular lamination. There was no sign of normal bone remodeling in cortical bone.Not only osteoblast but also chondrocyte concerns the skeletal growth. Using terminal differentiated chondrocyte, we intestigated how retionic acid stimulates their proliferation and induces dedifferentiation. From our experiments, we suggested that protein kinase C activity mediates the effect of retinoic acid in this chondrocyte.