The HIV Co-receptor CCR5 Regulates Osteoclast Function

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Dec 22

PMID 29263385

Citations 29

Authors

Ji-Won Lee

Akiyoshi Hoshino

Kazuki Inoue

Takashi Saitou

Shunsuke Uehara

Yasuhiro Kobayashi

Satoshi Ueha

Kouji Matsushima

Akira Yamaguchi

Yuuki Imai

Tadahiro Iimura

Affiliations

Soon will be listed here.

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.

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