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

我们研究了PDGF对人成骨细胞生长刺激的作用。PDGF刺激这些细胞的增殖，这一机制是由PDGF受体的酪氨酸激酶活性介导的，随后是细胞蛋白的磷酸化。研究成骨细胞在骨重建过程中的作用需要生物骨形成系统。将人骨源性成骨细胞注入扩散室，植入裸鼠腹腔。6-8周后，在膜滤器接触的细胞层内形成钙化体。在超微结构上，我们发现这种钙化体具有与体内骨形成相似的过程，骨髓组织中含有能向成骨方向分化的细胞。在此培养体系中，形成了包埋成骨细胞和骨细胞的矿化结节。电镜研究表明，这种矿化是由基质囊泡引发的，并沿着胶原纤维进行。以全身性骨质疏松为特征的石骨症，近年来对破骨细胞分化和骨重塑的研究受到重视。我们研究了一名患有石骨症的男子的下颌骨结构。骨髓腔几乎被骨质所占据，骨质层积极不规则。皮质骨无正常骨重建迹象，骨骼生长不仅与成骨细胞有关，也与软骨细胞有关。以终末分化的软骨细胞为材料，研究了维甲酸对软骨细胞增殖和去分化的影响。从我们的实验中，我们建议蛋白激酶C活性介导的效果，视黄酸在这个软骨细胞。

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.