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The HIV co-receptor CCR5 regulates osteoclast function

Author

Listed:
  • Ji-Won Lee

    (Ehime University)

  • Akiyoshi Hoshino

    (Tokyo Metropolitan Police Hospital)

  • Kazuki Inoue

    (Ehime University)

  • Takashi Saitou

    (Ehime University
    Ehime University Hospital)

  • Shunsuke Uehara

    (Matsumoto Dental University)

  • Yasuhiro Kobayashi

    (Matsumoto Dental University)

  • Satoshi Ueha

    (The University of Tokyo)

  • Kouji Matsushima

    (The University of Tokyo)

  • Akira Yamaguchi

    (Tokyo Dental College)

  • Yuuki Imai

    (Ehime University
    Ehime University Hospital
    Ehime University)

  • Tadahiro Iimura

    (Ehime University
    Ehime University
    Ehime University Hospital)

Abstract

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.

Suggested Citation

  • Ji-Won Lee & Akiyoshi Hoshino & Kazuki Inoue & Takashi Saitou & Shunsuke Uehara & Yasuhiro Kobayashi & Satoshi Ueha & Kouji Matsushima & Akira Yamaguchi & Yuuki Imai & Tadahiro Iimura, 2017. "The HIV co-receptor CCR5 regulates osteoclast function," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02368-5
    DOI: 10.1038/s41467-017-02368-5
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    Cited by:

    1. Jinbo Li & Zhenqiang Yao & Xin Liu & Rong Duan & Xiangjiao Yi & Akram Ayoub & James O. Sanders & Addisu Mesfin & Lianping Xing & Brendan F. Boyce, 2023. "TGFβ1+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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