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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.

集落刺激因子-1（CSF-1），又称巨噬细胞集落刺激因子，是单核吞噬系统细胞生长、分化、活化和存活所必需的因子。这种细胞因子已被证明是破骨细胞发育以及诱导破骨细胞祖细胞增殖和分化所必需的。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。在本体外研究中，当从大鼠长骨分离的破骨细胞与CSF-1孵育时，观察到具有大量细胞核的大TRAP阳性细胞的形成。这些在塑料上培养的大细胞与降钙素结合，并沿细胞边缘沿着形成F-肌动蛋白。在CSF-1的存在下，在牙本质切片上也观察到与这种大的TRAP阳性多核细胞的融合和小凹的形成。从塑料上的培养物获得的定量数据表明，在250 pM CSF-1存在下，破骨细胞的数量在72小时的过程中略微增加，而在不存在CSF-1的情况下，破骨细胞的数量在24小时后迅速减少，这证实了这种细胞因子是破骨细胞存活所必需的。每个破骨细胞的核数在与CSF-1孵育16小时后最大，即是在没有CSF-1的情况下发现的值的两倍。在250 pM-500 pM的浓度下观察到细胞因子对融合过程的最大作用。计算每个破骨细胞的细胞核分布的平均频率的中位数，在没有CSF-1的情况下，每个破骨细胞有4个细胞核，而在有CSF-1的情况下，每个破骨细胞有6个细胞核。酪氨酸激酶抑制剂染料木黄酮和除莠霉素A抑制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该过程。破骨细胞的融合过程可能会持续整个生命周期。