Human osteoblasts express functional CXC chemokine receptors 3 and 5:: Activation by their ligands, CXCL10 and CXCL13, significantly induces alkaline phosphatase and β-N-acetylhexosaminidase release
Human osteoblasts express functional CXC chemokine receptors 3 and 5:: Activation by their ligands, CXCL10 and CXCL13, significantly induces alkaline phosphatase and β-N-acetylhexosaminidase release
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DOI：
10.1002/jcp.10188
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发表时间：
2003-01-01
影响因子：
5.6
通讯作者：
Facchini, A
中科院分区：
文献类型：
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作者：
Lisignoli, G;Toneguzzi, S;Facchini, A
成骨细胞（Osteoblasts，OB）有助于维持骨稳态，并且其活性可受到位于骨陷窝中的免疫细胞的影响。我们通过逆转录-聚合酶链反应（RT-PCR）和流式细胞术研究了分离的人OBs中趋化因子受体的表达，并报告了一个新的发现，即OBs表达高水平的CXC趋化因子受体3（CXCR 3）和5（CXCR 5）。评估CXCR 3和CXCR 5的功能性试验表明，它们的配体CXCL 10和CXCL 13分别显著诱导β-N-乙酰氨基己糖苷酶的释放，β-N-乙酰氨基己糖苷酶是一种参与软骨内骨化和骨重建的酶，能够降解重要的细胞外基质成分。碱性磷酸酶活性，一个有用的指标，基质形成也上调CXCL 10和CXCL 13。然而，OB激活这些配体不影响OB增殖。百日咳博德特氏菌毒素和中和性抗CXCR 3/抗CXCR 5单克隆抗体分别阻断CXCL 10和CXCL 13诱导。我们还证实了CXCL 10和CXCL 13在人骨组织活检中的表达。这些结果表明，CXCR 3/CXCL 10和CXCR 5/CXCL 13受体-配体对可能通过特异性上调参与骨重建过程的两种酶在OB活性中发挥重要作用。此外，我们的数据表明，OBs可能通过这两种酶的联合作用在骨形成的调节中发挥作用。
Osteoblasts (OBs) contribute to the maintenance of, bone homeostasis and their activity can be influenced by immune cells localized in bone lacunae. We investigated the expression of the chemokine receptors in isolated human OBs by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, and report a novel finding, namely, that OBs express high levels of CXC chemokine receptor 3 (CXCR3) and 5 (CXCR5). Functional assays to evaluate CXCR3 and CXCR5 demonstrated that their ligands-CXCL10 and CXCL13, respectively-significantly induce the release of beta-N-acetylhexosaminidase, an enzyme involved in endochondral ossification and bone remodeling able to degrade important extracellular matrix components. Alkaline phosphatase activity, a useful index of matrix formation was also up-regulated by CXCL10 and CXCL13. However, OB activation by these ligands does not affect OB proliferation. Both Bordetella pertussis toxin and neutralizing anti-CXCR3/anti-CXCR5 monoclonal antibodies block CXCL10 and CXCL13 induction, respectively. We also demonstrated the expression of CXCL10 and CXCL13 in human bone tissue biopsies. These results indicate that both CXCR3/CXCL10 and CXCR5/CXCL13 receptor-ligand pairs may play an important role in OB activity through the specific up-regulation of two enzymes, which are involved in the bone remodeling process. Moreover, our data suggest that OBs may play a role in the modulation of bone formation through the combined action of these two enzymes.