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刺激了这些细胞的增殖，这一机制是通过PDGF受体酪氨酸激酶活性和细胞蛋白磷酸化介导的。我们也在研究PDGF在这些细胞中诱导基因表达的作用。生物成骨系统是研究成骨细胞在骨重塑中的作用的必要条件。将人骨源性成骨细胞注入扩散室，并腹腔植入裸鼠体内。6 ~ 8周后，接触膜滤器的细胞层形成钙化体。超微结构显示，钙化体与体内骨形成过程相似。骨髓组织中含有能向成骨方向分化的细胞。在这个培养体系中，形成了包埋成骨细胞和骨细胞的矿化结节。通过电镜研究，这种矿化被认为是与基质囊泡相关的，并沿着胶原原纤维进展。骨质疏松是一种以系统性骨硬化为特征的疾病，破骨细胞分化和骨重塑已引起人们的关注。我们研究了一个患有骨质疏松症的人的下颌骨结构。骨髓腔几乎被硬化骨占据，层压非常不规则。皮质骨未见正常骨重塑的迹象。骨的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研究对象，研究了酸如何刺激其增殖并诱导其去分化。从我们的实验中，我们认为蛋白激酶C活性介导视黄酸在软骨细胞中的作用。

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.