Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat:: a key role for CCL9 (MIP-1γ) in osteoclastogenesis in vivo and in vitro
Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat:: a key role for CCL9 (MIP-1γ) in osteoclastogenesis in vivo and in vitro
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DOI：
10.1182/blood-2005-08-3365
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发表时间：
2006-03-15
期刊：
影响因子：
20.3
通讯作者：
Odgren, PR
中科院分区：
文献类型：
--
作者：
Yang, MH;Mailhot, G;Odgren, PR
破骨细胞在全身和局部控制下从造血前体分化而来。趋化因子和受体引导白细胞在全身的交通，并可能有助于调节特定部位的骨吸收。研究了集落刺激因子1 （CSF-1）诱导无牙（tl/tl）大鼠体内破骨细胞快速分化过程中骨基因的表达。采用高密度芯片对csf -1处理后的大鼠长骨RNA进行分析。第2天出现抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞，第4天达到峰值，第6天随骨髓间隙扩大略有下降。TRAP和组织蛋白酶K mRNA与细胞计数平行。我们检查了阵列上的所有趋化因子和受体mrna。CCL9及其受体CCR1、调节受体c-Fms （CSF-1受体）和RANK（核因子κ B受体激活剂）在第2天被强烈诱导并达到峰值。其他趋化因子和受体几乎没有或没有显著变化。原位杂交和免疫组织化学显示CCL9在第2天出现在小的、未成熟的破骨细胞中，随后在成熟细胞中出现。抗ccl9抗体可抑制体外培养的破骨细胞分化，并显著抑制csf -1处理的tl/tl大鼠的破骨细胞反应。虽然体外实验中有多种趋化因子参与破骨细胞的形成，但本文首次对体内破骨细胞分化过程中的趋化因子和受体进行了系统分析，强调了CCL9在这一过程中的关键作用。
Osteoclasts differentiate from hematopoietic precursors under systemic and local controls. Chemokines and receptors direct leukocyte traffic throughout the body and may help regulate site-specific bone resorption. We investigated bone gene expression in vivo during rapid osteoclast differentiation induced by colony-stimulating factor 1 (CSF-1) in Csf1-null toothless (tl/tl) rats. Long-bone RNA from CSF-1-treated tl/tl rats was analyzed by high-density microarray over a time course. TRAP (tartrate-resistant acid phosphatase)-positive osteoclasts appeared on day 2, peaked on day 4, and decreased slightly on day 6, as marrow space was expanding. TRAP and cathepsin K mRNA paralleled the cell counts. We examined all chemokine and receptor mRNAs on the arrays. CCL9 was strongly induced and peaked on day 2, as did its receptor, CCR1, and regulatory receptors c-Fms (CSF-1 receptor) and RANK (receptor activator of nuclear factor kappa B). Other chemokines and receptors showed little or no significant changes. In situ hybridization and immunohistochemistry revealed CCL9 in small, immature osteoclasts on day 2 and in mature cells at later times. Anti-CCL9 antibody inhibited osteoclast differentiation in culture and significantly suppressed the osteoclast response in CSF-1-treated tl/tl rats. While various chemokines have been implicated in osteoclastogenesis in vitro, this first systematic analysis of chemokines and receptors during osteoclast differentiation in vivo highlights the key role of CCL9 in this process.