Effect of CFS-1 on osteoclast and its precursor cells

CFS-1对破骨细胞及其前体细胞的影响

基本信息

批准号：
07672028
负责人：
YAMADA Shoji
金额：
$ 1.47万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Colony-stimulating factor-1 (CSF-1), Also called macrophage colony-stimulating factor, is required for growth, differentiation activation, and survival of cells of the mononuclear phagocytic system. This cytokine has been shown to be essential foe osteoclast development as well as for inducing both proliferation and differentiation of osteoclast progenitors. It also sustains survival of mature osteoclasts and stimulates spreading and migration of these cells. In the present in vitro study, the formation of large TRAP-positive cells with a high number of nuclei was observed when osteoclasts isolated from rat long bones were incubated with CSF-1. These large cells, cultured on plastic, bind calcitonin and form F-actin along the edges of the cells. Fusion to such large TRAP-positive multinucleated cells in the presence of CSF-1 and the formation of pits were also observed on dentine slices. Quantitative data obtained from cultures on plastic demonstrated that the number of osteoclasts slightly increased in the course of 72 hrs in the presence of 250 pM CSF-1, whereas it decreased rapidly after 24 hrs in the absence of CSF-1, which confirms that this cytokine is required for the survivai of osteoclasts. The number of nuclei per osteoclast was maximal after 16 hrs incubation with CSF-1, namely twice the value found in the absence of CSF-1. The maximal effect of the cytokine on the fusion process was observed at a concentration of 250 pM-500pM.A calculation of the medians of the average frequency of nuclei distribution per osteoclast resulted in 4 nuclei per osteoclast in the absence, and 6 in the presence of CSF-1. Genistein and herbimycin A,inhibitors of tyrosine kinases, inhibited the fusion induced by CSF-1. The data suggest that CSF-1 induces osteoclast fusion, and that tyrosine kinase (s) are involved in this process. The fusion process may continue throughout the entire life on an osteoclast.

刺激菌落刺激因子1（CSF-1），也称为巨噬细胞刺激因子，是生长，分化激活和单核吞噬系统细胞存活所必需的。该细胞因子已被证明是必需的敌人破骨细胞的发育，以及诱导破骨细胞祖细胞的增殖和分化。它还维持成熟破骨细胞的存活，并刺激这些细胞的扩散和迁移。在目前的体外研究中，当从大鼠长骨与CSF-1中孵育的破骨细胞时，观察到大量核阳性细胞的形成。这些大细胞在塑料上培养，结合降钙素并沿细胞边缘形成F-肌动蛋白。在CSF-1的存在下，还观察到在牙本质切片上融合到如此大的TRAP阳性多核细胞和凹坑的形成。从塑料上培养的培养物获得的定量数据表明，在CSF-1 250 pm的情况下，在72小时的过程中，破骨细胞的数量略有增加，而在不存在CSF-1的情况下，在24小时后，在不存在CSF-1的情况下，它迅速减少，这证实了这种细胞因子对于Otosteoclasts的生存所需的细胞因子所需。在与CSF-1孵育16小时后，每骨细胞的核数量最大，即在没有CSF-1的情况下发现的值是两倍。在250 pm-500p的浓度下观察到细胞因子对融合过程的最大作用。计算平均每个破骨细胞核分布的平均频率的中位数导致每骨细胞4个核在不存在的情况下，在CSF-1的存在下为6个核。染料木黄素和雄性霉素A（酪氨酸激酶的抑制剂）抑制了CSF-1诱导的融合。数据表明CSF-1诱导破骨细胞融合，并且酪氨酸激酶参与了这一过程。融合过程可能会在整个破骨细胞上持续下去。