Chick osteocyte-derived protein inhibits osteoclastic bone resorption
Chick osteocyte-derived protein inhibits osteoclastic bone resorption
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DOI：
10.1042/bj3220245
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发表时间：
1997-02-15
影响因子：
4.1
通讯作者：
Kumegawa, M
中科院分区：
文献类型：
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作者：
MaejimaIkeda, A;Aoki, M;Kumegawa, M
为了研究骨细胞在骨吸收中的作用，我们使用来自小鼠的未分级的骨细胞在凹坑形成试验中检查了来自纯化的鸡颅骨骨细胞的匀浆和条件培养基。骨细胞匀浆明显抑制陷窝的形成，而骨细胞条件培养液则无此作用。这种抑制活性不是匀浆细胞毒性的结果。一种新的骨吸收抑制蛋白纯化胶原酶消化的鸡颅骨片段富含骨细胞。抑制蛋白，分子量为18.5 kDa，表现出显着的剂量依赖性抑制小坑形成的未分级的骨细胞从小鼠和兔，和人巨大的肿瘤细胞。在没有其他效应细胞的情况下，这种蛋白质也抑制了在凹坑形成试验中纯化的破骨细胞的骨吸收活性。将蛋白质显微注射到破骨细胞中引起细胞中的足体的破坏。该蛋白N端25个氨基酸序列与Rho-GTP解离抑制剂的部分序列同源性为68%。因此鸡颅骨骨细胞可能参与破骨细胞对骨吸收的调节。
In order to investigate the role of osteocytes in bone resorption, we examined the homogenate and conditioned medium from purified chick calvarial osteocytes in a pit-formation assay using unfractionated bone cells from mice. The osteocyte homogenate markedly inhibited pit formation, whereas the conditioned medium of osteocytes had no effect. This inhibitory activity was not the result of cytotoxicity of the homogenate. A novel bone-resorption-inhibitory protein was purified from collagenase-digested chick calvarial fragments enriched in osteocytes. The inhibitory protein, of molecular mass 18.5 kDa, showed significant dose-dependent inhibition of pit formation by unfractionated bone cells from mice and rabbits, and by human giant tumour 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 showed 68% identity to a part of Rho-GTP-dissociation inhibitor. Thus chick calvarial osteocytes may be involved in the regulation of bone resorption by osteoclasts.