在破骨细胞形成过程中，RANKL通过JAK2 / STAT3信号通路下调细胞表面CXCR6表达。,Biochemical and Biophysical Research Communications

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在破骨细胞形成过程中，RANKL通过JAK2 / STAT3信号通路下调细胞表面CXCR6表达。
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2012-11-13 , DOI: 10.1016/j.bbrc.2012.10.122
Changhong Li ₁ , Jinxia Zhao , Lin Sun , Zhongqiang Yao , Rui Liu , Jiansheng Huang , Xiangyuan Liu

Affiliation

核因子-κB配体（RANKL）的受体激活剂是肿瘤坏死因子（TNF）家族的成员，在破骨细胞的分化和功能中起着至关重要的作用。最近已显示趋化因子及其受体在破骨细胞形成中起关键作用，但是，CXCL16-CXCR6是否在RANKL介导的破骨细胞形成中起着未知的作用。在这项研究中，我们首先报道了RANKL以剂量依赖的方式降低CXCR6，这可能是由于CXCL16诱导的Akt和STAT3信号的失活所致。有趣的是，RANKL介导的CXCR6还原可能与磷酸化激活STAT3有关。当JAK2 / STAT3抑制剂AG490阻止STAT3激活时，RANKL无法在破骨细胞形成过程中关闭CXCR6表达。然而，单独的CXCL16不会增加RANKL介导的破骨细胞分化，也不会改变RANKL受体RANK mRNA的表达。这些结果表明，CXCL16-CXCR6的减少在RANKL介导的破骨细胞形成中至关重要，这主要是通过激活JAK2 / STAT3信号传导来实现的。CXCL16-CXCR6轴可能成为类风湿性关节炎和骨质疏松症等骨吸收疾病的治疗干预的新目标。

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RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis.

The receptor activator of nuclear factor-κB ligand (RANKL), as a member of the tumor necrosis factor (TNF) family, plays an essential role in osteoclast differentiation and function. Chemokines and their receptors have recently been shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6 plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we first reported that RANKL decreased CXCR6 in a dose-dependent manner, which may be through deactivation of Akt and STAT3 signaling induced by CXCL16. Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3 inhibitor AG490, RANKL failed to shut down CXCR6 expression during osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression. These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL-mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3 signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis and osteoporosis.

更新日期：2019-11-01

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