CXCL12 chemokine up-regulates bone resorption and MMP-9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patients
CXCL12 chemokine up-regulates bone resorption and MMP-9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patients
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DOI：
10.1002/jcp.10445
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发表时间：
2004-05-01
影响因子：
5.6
通讯作者：
Lisignoli, G
中科院分区：
文献类型：
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作者：
Grassi, F;Cristino, S;Lisignoli, G
趋化因子参与了许多炎症病理过程，其中一些在破骨细胞发育的调节中起着关键作用。因此，我们评估了CXCL12趋化因子在破骨细胞分化和功能中的作用，并分析了其在类风湿关节炎(RA)患者滑膜和骨组织活检组织中的表达。在有或无CXCL12的条件下，用CD11b阳性细胞的RANKL和M-CSF在体外诱导7d获得破骨细胞。抗酒石酸酸性磷酸酶(TRAP)染色分析破骨细胞总数，PIT法检测骨吸收活性。用酶联免疫吸附试验检测基质金属蛋白酶-9和基质金属蛋白酶-1的释放。免疫组织化学方法检测CXCL12在RA患者活检组织中的表达。在10 nM浓度的CXCL12存在下获得的破骨细胞在凹坑吸收试验中显示出非常显著的骨吸收活性增加，而成熟破骨细胞的总数没有受到影响。骨吸收增加与基质金属蛋白酶-9的过度表达有关。类风湿性关节炎(RA)和骨关节炎(OA)滑膜和骨组织标本中CXCL12的免疫组织化学染色显示，在炎症条件下，CXCL12的表达水平显著增加。CXCL12趋化因子通过诱导骨吸收活性和特异性释放基质金属蛋白酶-9，对成熟破骨细胞具有明显的激活作用。此外，由于RA患者的骨和滑膜活检显示CXCL12表达升高，这些发现可能为全面阐明炎症性疾病过程中调节破骨细胞功能的复杂网络提供有用的工具。J.细胞。物理。199：244-251,2004。(C)2003年Wiley-Liss，Inc.
Chemokines are involved in a number of inflammatory pathologies and some of them show a pivotal role in the modulation of osteoclast development. Therefore, we evaluated the role of CXCL12 chemokine on osteoclast differentiation and function and we analyzed its expression on synovial and bone tissue biopsies from rheumatoid arthritis (RA) patients. Osteoclasts were obtained by 7 days in vitro differentiation with RANKL and M-CSF of CD11b positive cells in the presence or absence of CXCL12. The total number of osteoclast was analyzed by Tartrate-resistant acid phosphatase (TRAP)-staining and bone-resorbing activity was assessed by pit assay. MMP-9 and TIMP-1 release was evaluated by ELISA assay. CXCL12 expression on biopsies from RA patients was analyzed by immuno-histochemistry. Osteoclasts obtained in the presence of CXCL12 at 10 nM concentration displayed a highly significant increase in bone-resorbing activity as measured by pit resorption assay, while the total number of mature osteoclasts was not affected. The increased resorption is associated with overexpression of MMP-9. Immunostaining for CXCL12 on synovial and bone tissue biopsies from both rheumatoid arthritis (RA) and osteoarthritis (OA) samples revealed a strong increase in the expression levels under inflammatory conditions. CXCL12 chemokine showed a clear activating role on mature osteoclast by inducing bone-resorbing activity and specific MMP-9 enzymatic release. Moreover, since bone and synovial biopsies from RA patients showed an elevated CXCL12 expression, these findings may provide useful tools for achieving a full elucidation of the complex network that regulates osteoclast function in course of inflammatory diseases. J. Cell. Physiol. 199: 244-251, 2004. (C) 2003 Wiley-Liss, Inc.