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- Title
The HIV co-receptor CCR5 regulates osteoclast function.
- Authors
Ji-Won Lee; Akiyoshi Hoshino; Kazuki Inoue; Takashi Saitou; Shunsuke Uehara; Yasuhiro Kobayashi; Satoshi Ueha; Kouji Matsushima; Akira Yamaguchi; Yuuki Imai; Tadahiro Iimura
- 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.
- Subjects
CHEMOKINES; CHEMOKINE receptors; HIV; BONE diseases; HIV infection transmission; BONE cells; OSTEOCLASTS; OSTEOPOROSIS
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-02368-5