Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES
Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES
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DOI：
10.1002/jcb.20649
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发表时间：
2006-02-15
影响因子：
4
通讯作者：
Morrison, NA
中科院分区：
文献类型：
--
作者：
Kim, MS;Magno, CL;Morrison, NA
趋化因子MCP-1和RANTES是诱导真正的骨吸收的人破骨细胞从单核细胞前体在体外分化。此外，MCP-1和RANTES可以刺激细胞分化，具有破骨细胞的视觉外观，是多核的并且对酒石酸盐抗性酸性磷酸酶（TRAP+）呈阳性。我们在此表明，MIP 1 α在人破骨细胞分化过程中也被RANKL有效诱导，并且在不存在RANKL的情况下，该趋化因子也诱导TRAP+多核细胞的形成。MIP 1 α能够克服GM-CSF对破骨细胞分化的有效抑制，允许细胞通过TRAP+多核细胞，但这些细胞不能形成再吸收陷窝。趋化因子受体CCR 2b和CCR 4被RANKL强效诱导（分别为12.6和49倍，P = 4.0 x 10（-7）和4.0 x 10（-8）），而CCR 1和CCR 5未受调节。在不存在RANKL的情况下，趋化因子处理也诱导MCP-1、RANTES和MIP 1 α。出乎意料的是，在不存在RANKL的情况下，用MCP-1处理导致CCR 4诱导458倍（P = 1.0 x 10（-10）），而RANTES处理导致两倍抑制（P = 1.0 x 10（-4））。由于CCR 2b和CCR 4是MCP-1受体，因此这些数据支持使用RANKL分化的人破骨细胞中存在MCP-1自分泌环。
Chemokines MCP-1 and RANTES are induced when authentic bone resorbing human osteoclasts differentiate from monocyte precursors in vitro. in addition, MCP-1 and RANTES can stimulate the differentiation of cells with the visual appearance of osteoclasts, being multinuclear and positive for tartrate resistance acid phosphatase (TRAP+). We show here that MIP1 alpha is also potently induced by RANKL during human osteoclast differentiation and that this chemokine also induces the formation of TRAP+ multinucleated cells in the absence of RANKL. MIP1 alpha was able to overcome the potent inhibition of GM-CSF on osteoclast differentiation, permitting the cells to pass through to TRAP+ multinuclear cells, however these were unable to form resorption pits. Chemokine receptors CCR2b and CCR4 were potently induced by RANKL (12.6- and 49-fold, P = 4.0 x 10(-7) and 4.0 x 10(-8), respectively), while CCR1 and CCR5 were not regulated. Chemokine treatment in the absence of RANKL also induced MCP-1, RANTES and MIP1 alpha. Unexpectedly, treatment with MCP-1 in the absence of RANKL resulted in 458-fold induction of CCR4 (P = 1.0 x 10(-10)), while RANTES treatment resulted in twofold repression (P = 1.0 x 10(-4)). Since CCR2b and CCR4 are MCP-1 receptors, these data support the existence of an MCP-1 autocrine loop in human osteoclasts differentiated using RANKL.