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Bone resorption mechanisms on LPS in human osteoclast-like cells formation system

人破骨细胞样细胞形成系统中LPS的骨吸收机制

基本信息

批准号：
03670900
负责人：
KURIHARA Noriyoshi
金额：
$ 0.32万
依托单位：
Meikai University School of Dentistry
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670900/
关键词：
LPS Osteoclast Osteoclast-precursor ILー1(インタ-ロイキンー1)

项目摘要

Lipopolysaccharides(LPS) has very important roles in occuring periodontal disease and bone resorption of alveoral bone. However, no studies have been reported in which LPS induce osteoclasts formation in human cells. Recently we have shown that long term human umbilical cord blood cultures can be adapted to form multinucleated cell(MNC) that express an osteoclast phenotype (multinucleated, presence of tartrate resistant acid phosphatase activity, contraction in response to calcitonin, calcitonin receptor, formation of resorption lacunae on calcified matrices and cross-reactivity with the mAb 23C6(CD-51), which preferentially binds osteoclasts in bone biopsy specimens). This culture suggested that the CFU-GM (the granulocyte-macrophage progentor cells) is the pro-genitor cell for osteoclast. In this experiment, we studied the effect of LPS on osteoclasts formation. Addition of LPS (10-100ng/ml) to these cultures significantly increase MNC formation, with 50% of the MNC expressing an antigen which cross-reacts with the mAb 23C6. Addition of anti-human IL-1 to cultures treated with LPS totally inhibited the increase in MNC formation stimulated by LPS. Further, conditiond madia from these cultures exposed to LPS contained elevated levels of IL-1alphaand beta (47pg/ml of IL-1alpha and 31pg/ml of IL-1beta compared to under 5pg/ml in control cultures 12h. after LPS addition). These results strongly suggested that LPS significantly stimulated MNC formation in human cord blood cultures, and preferentially stimulated formation of MNC expressing the antigen recognized by 23C6 mAb. We further indicate that the effects of LPS in this system appear to be mediated by induction ofIL-1, a potent stimulator of osteoclasts formation.

脂多糖（Lipopolysaccharides，LPS）在牙周病的发生和牙槽骨的骨吸收中起重要作用。然而，还没有研究报道LPS诱导人细胞中破骨细胞的形成。最近，我们发现，长期的人脐带血培养可以形成表达破骨细胞表型的多核细胞（MNC（多核，存在抗酒石酸酸性磷酸酶活性，对降钙素、降钙素受体的反应性收缩，钙化基质上形成再吸收陷窝以及与mAb 23 C6（CD-51）的交叉反应性，其优先结合骨活检样本中的破骨细胞）。本实验结果表明，CFU-GM（粒-巨噬祖细胞）是破骨细胞的祖细胞。本实验研究了LPS对破骨细胞形成的影响。向这些培养物中添加LPS（10- 100 ng/ml）显著增加MNC形成，其中50%的MNC表达与mAb 23 C6交叉反应的抗原。在LPS处理的培养物中加入抗人IL-1完全抑制了LPS刺激的MNC形成的增加。此外，来自这些暴露于LPS的培养物的条件培养基含有升高水平的IL-1 α和IL-1 β（47 pg/ml的IL-1 α和31 pg/ml的IL-1 β，而对照培养物12小时中低于5 pg/ml。加入LPS后）。这些结果强烈地表明，LPS显著刺激人脐带血培养物中的MNC形成，并且优先刺激表达23 C6 mAb识别的抗原的MNC的形成。我们进一步指出，LPS在该系统中的作用似乎是通过诱导破骨细胞形成的有效刺激因子IL-1介导的。