The HIV co-receptor CCR5 regulates osteoclast function.
The HIV co-receptor CCR5 regulates osteoclast function.
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DOI：
10.1038/s41467-017-02368-5
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发表时间：
2017-12-20
影响因子：
16.6
通讯作者：
Iimura T
中科院分区：
文献类型：
--
作者：
Lee JW;Hoshino A;Inoue K;Saitou T;Uehara S;Kobayashi Y;Ueha S;Matsushima K;Yamaguchi A;Imai Y;Iimura T
C-C趋化因子受体5（CCR 5）是HIV的共受体。流行病学研究结果表明，CCR 5的功能丧失与骨破坏性疾病和HIV传播的发病率降低相关。然而，目前尚不清楚CCR 5是否参与调节骨细胞的功能，以及免疫细胞的功能。在这里，我们表明，使用特异性抗体阻断CCR 5会损害体外人破骨细胞的功能。Ccr 5缺陷（Ccr 5 −/−）小鼠表现为破骨细胞功能障碍，并且对核因子κ B配体受体激活剂（RANKL）诱导的骨质疏松症具有抗性，RANKL可独立于炎症和免疫调节途径引发骨质疏松症。此外，Ccr 5缺乏会损害破骨细胞的细胞运动和骨吸收活性，这与podosomes和粘附复合物分子（包括Pyk 2）的重排有关。总的来说，这些数据提供了证据表明，CCR 5通过破骨细胞的功能调节在骨破坏性疾病中发挥重要作用。CCR 5是HIV的辅助受体，功能丧失与HIV的发病率降低有关，但也与骨破坏性疾病有关。在这里，作者表明，CCR 5的消融损害破骨细胞功能，并提高小鼠模型对骨质疏松症的抵抗力。
C–C chemokine receptor 5 (CCR5) is a co-receptor of HIV. Epidemiological findings suggest that the functional loss of CCR5 is correlated with a lower incidence of bone-destructive diseases as well as of HIV transmission. However, it is not clear whether CCR5 is involved in regulation of the function of bone cells, in addition to that of immune cells. Here we show that blockade of CCR5 using specific antibodies impairs human osteoclast function in vitro. Ccr5-deficient (Ccr5 −/−) mice presented with dysfunctional osteoclasts and were resistant to osteoporosis induced by receptor activator of nuclear factor kappa-B ligand (RANKL), which triggers osteoporosis independently of inflammatory and immunomodulatory pathways. Furthermore, Ccr5 deficiency impairs the cellular locomotion and bone-resorption activity of osteoclasts, which is associated with the disarrangement of podosomes and adhesion complex molecules including Pyk2. Overall, the data provides evidence that CCR5 has an essential role in bone-destructive conditions through the functional regulation of osteoclasts. CCR5 is a co-receptor for HIV, and loss of function is associated with lower incidence of HIV but also with bone-destructive diseases. Here the authors show that ablation of CCR5 impairs osteoclast function and improves resistance to osteoporosis in mouse models.
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