The HIV co-receptor CCR5 regulates osteoclast function.

Lee JW1, Hoshino A2, Inoue K3, Saitou T4,5, Uehara S6, Kobayashi Y7, Ueha S8, Matsushima K8, Yamaguchi A9, Imai Y3,10,11, Iimura T12,13,14
Source: Nat Commun.
Publication Date: ()
Issue: 8: 2226
Cells used in publication:
Mesenchymal stem cell (MSC), human
Species: human
Tissue Origin: bone marrow
Osteoclast precursor (OCP), human
Species: human
Tissue Origin: bone marrow


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