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Functions of osteocytes in bone metabolism

骨细胞在骨代谢中的功能

基本信息

批准号：
07457431
负责人：
KUMEGAWA Masayoshi
金额：
$ 4.54万
依托单位：
Meikai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457431/
关键词：
Osteocytes Inhibition of bone resorption Rho-GDI like protein Ca receptor Vitamin D_3 Pho-GDIタンパク質破骨細胞抑制因子

项目摘要

I.In order to investigate roles of osteocytes in bone resorption, the homogenate and conditioned medium of purified chick calvarial osteocytes were examined in a pit formation assay using unfractionated bone cells from mice. The osteocyte homogenate markedly inhibited the pit formation, whereas the conditioned medium of the cells had no effect on the pit formatin. The inhibitory activity was not a result of cytotoxicity of the homogenate. In this study, a bone-resorption inhibitory protein was purified from collagenase-digested chick calvarial fragments enriched in osteocytes. The inhibitory protein, 18.5kDa, showed a significant dose-dependent inhibition of the pit formation by unfractionated bone cells from mice and rabbits, and by human giant cell tumor cells. This protein also inhibited the bone-resorbing activity of purified osteoclasts in the pit formation assay in the absence of other effector cells. Microinjection of the protein into osteoclasts caused disruption of the podosomes in the cells. The N-terminal 25-amino acid sequence of the protein was 68% homologous to a part of Rho-GDI.Osteocytes may be involved in the regulatory mechanism of bone resorption by osteoclasts.II.Vitamin D_3 regulates the amount of calcium receptor (CaSR) mRNA Vitamin D_3 decreases the amount of CaSR mRNA in occipital bone, but the hormone increases that of CaSR mRNA in long bone and kidney. These results indicate the presence of tissue specific regulation in CaSR by Vitamin D_3.

为了研究骨细胞在骨吸收中的作用，我们使用未分离的小鼠骨细胞对纯化鸡颅骨骨细胞的匀浆和条件培养基进行了窝形成实验。骨细胞匀浆明显抑制窝形成，而细胞条件培养基对窝形成蛋白无影响。抑制活性不是匀浆细胞毒性的结果。本研究从富含骨细胞的胶原酶消化的鸡颅骨碎片中纯化出一种骨吸收抑制蛋白。该抑制蛋白为18.5kDa，对小鼠和兔未分离骨细胞以及人类巨细胞肿瘤细胞的窝形成具有明显的剂量依赖性抑制作用。在没有其他效应细胞的情况下，该蛋白也抑制了纯化破骨细胞的骨吸收活性。将该蛋白显微注射到破骨细胞中，可导致细胞内足小体的破坏。该蛋白的n端25个氨基酸序列与Rho-GDI的一部分同源性为68%。骨细胞可能参与破骨细胞骨吸收的调节机制。ii .维生素D_3调节钙受体（CaSR） mRNA的量维生素D_3降低枕骨中CaSR mRNA的量，而激素增加长骨和肾脏中CaSR mRNA的量。这些结果表明维生素D_3在CaSR中存在组织特异性调节。