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Application to the elucidation and diagnosis of inflammatory bone resorption using the chemokine receptor expression pattern.

使用趋化因子受体表达模式应用于炎症性骨吸收的阐明和诊断。

基本信息

批准号：
21592633
负责人：
OKAMATSU Yoshimasa
金额：
$ 2.91万
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：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

Bone resorption by osteoclast involves initial stages of osteoclasts precursor cells migration, followed by differentiation into mature osteoclasts. Chemokine play essential roles in the chemotaxis to hematopoietic cells. In this grant, we established the effect of relationship chemokines to chemokine receptors on receptor activator of NF-kB ligand (RANKL)-stimulated osteoclast differentiation. CCL7 and CCL25 were induced from IL-1-and VitaminD3-stimulated ST2 cells, as osteoblastic cell line, simultaneously with RANKL production. On the other hand, CCR2 and CCR9, are well known CCL7 receptor and CCL25 receptor respectively, expressed in RAW264.7 cells, as osteoclast precursor cells. Neutralization of CCL7 and CCL25 antibody reduced RANKL-stimulated osteoclast differentiation by 50% approximately. Further, recombinant of CCL7 and CCL25 up-regulated the number of RANKL-induced multinuclear cells. Same results obtained from RANKL-stimulated bone marrow cells. Transwell migration activity in response to CCL7 was observed only when RANKL-treated RAW264.7 cells were used. CCL7 also significantly increased expression of RANK and NFATc1, but not Fra1 and AP1 in RANKL-treated RAW264.7 cells. Further, CCL7 significantly increased luciferase activity of NF-kB and NFAT reporter.Taken together, these results suggest that CCL7-CCR2(or CCR1) may plays an important role in the RANKL-induced osteoclast differentiation, most likely osteoclast precursor cells migration.

破骨细胞的骨吸收包括破骨细胞前体细胞迁移的初始阶段，随后分化为成熟的破骨细胞。趋化因子在造血细胞的趋化过程中起重要作用。在这项研究中，我们建立了趋化因子与趋化因子受体对NF-κ B配体受体激活剂（RANKL）刺激的破骨细胞分化的影响。从IL-1和维生素D3刺激的ST 2细胞（作为成骨细胞系）诱导CCL 7和CCL 25，同时产生RANKL。另一方面，CCR 2和CCR 9分别是众所周知的CCL 7受体和CCL 25受体，作为破骨细胞前体细胞在RAW 264.7细胞中表达。CCL 7和CCL 25抗体的中和使RANKL刺激的破骨细胞分化减少约50%。此外，CCL 7和CCL 25的重组体上调了RANKL诱导的多核细胞的数量。从RANKL刺激的骨髓细胞获得相同结果。仅当使用RANKL处理的RAW 264.7细胞时，观察到对CCL 7的Transwell迁移活性。在RANKL处理的RAW264.7细胞中，CCL 7也显著增加RANK和NFATc 1的表达，但不增加Fra 1和AP 1的表达。这些结果表明，CCL 7-CCR 2（或CCR 1）可能在RANKL诱导的破骨细胞分化中起重要作用，最可能是破骨细胞前体细胞迁移。