A STUDY OF THE REGULATORY MECHANISM OF CYTOKINES ON OSTEOCLASTIC BONE RESORPTION IN POSTMENOPAUSAL OSTEOPOROSIS

破骨细胞是来源于造血细胞的多核细胞。成骨细胞/基质细胞系对于破骨细胞的发生是必不可少的，它通过产生前体细胞存活所需的细胞因子(如M-CSF)和破骨细胞前体细胞与细胞之间的直接相互作用，对破骨细胞前体的终末分化至关重要。我们已经证明雌激素缺乏可能影响成骨细胞/基质细胞，间接导致破骨细胞形成的增加。在这项研究中，我们首先研究了M-CSF在破骨细胞前体细胞群生成中的作用。然后，我们重点研究了基质细胞通过细胞间相互作用的支持机制。在小鼠基质细胞系ST2和造血细胞的共培养体系中，我们重点研究了破骨细胞生成的传代依赖性减少的现象。我们试图分离基因表达与支持破骨细胞生成能力相关的分子。为了评估破骨细胞发生过程中涉及的细胞因子和基因在骨组织中的表达，我们建立了脱钙骨标本的原位杂交体系。我们已经在各种国际和国内会议上公布了我们的数据，并出版了许多学术论文。

Osteoclasts are multinucleated cells derived from hematopoietic cells. Osteoblastic/stromal cell lineage is indispensable for osteoclastogenesis by producing cytokines (e.g.M-CSF) for the survival of precursor cells and via the direct cell-to-cell interaction essential for the terminal differentiation of osteoclast precursors.We have shown the possibility that estrogen difficiency affects on osteoblastic/stromal cells and indirectly causes the increase of the formation of osteoclast. In this study, at first we investigated the role of M-CSF on the generation of the osteoclast precursor population. Then we focused on the supporting mechanism of stromal cells via cell-to-cell interaction. We focused the phenomenon of the passage-dependent reduction of osteoclastogenesis in the co-culture system of mouse stromal cell line.ST2, and hemopoietic cells. We attempted to isolate the molecules of which gene expression is associated to the ability of supporting osteoclastogenesis.To assess the expression of cytokines and genes invloved in osteoclastogenesis on the bone tissues, we set up the system of in situ hybridization using decalcified bone specimen. We have presented our data at various international as well as domestic meetings, and publish a lot of scientific papaers for academic jurnals.