| First Author | Wauquier F | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 9 | Pages | 6542-51 |
| PubMed ID | 23335512 | Mgi Jnum | J:196896 |
| Mgi Id | MGI:5490173 | Doi | 10.1074/jbc.M112.429084 |
| Citation | Wauquier F, et al. (2013) The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem 288(9):6542-51 |
| abstractText | The mechanisms linking fat intake to bone loss remain unclear. By demonstrating the expression of the free fatty acid receptor G-coupled protein receptor 40 (GPR40) in bone cells, we hypothesized that this receptor may play a role in mediating the effects of fatty acids on bone remodeling. Using micro-CT analysis, we showed that GPR40(-/-) mice exhibit osteoporotic features suggesting a positive role of GPR40 on bone density. In primary cultures of bone marrow, we showed that GW9508, a GRP40 agonist, abolished bone-resorbing cell differentiation. This alteration of the receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation occurred via the inhibition of the nuclear factor kappaB (NF-kappaB) signaling pathway as demonstrated by decrease in gene reporter activity, inhibitor of kappaB kinase (IKKalpha/beta) activation, inhibitor of kappaB (IkBalpha) phosphorylation, and nuclear factor of activated T cells 1 (NFATc1) expression. The GPR40-dependent effect of GW9508 was confirmed using shRNA interference in osteoclast precursors and GPR40(-/-) primary cell cultures. In addition, in vivo administration of GW9508 counteracted ovariectomy-induced bone loss in wild-type but not GPR40(-/-) mice, enlightening the obligatory role of the GPR40 receptor. Then, in a context of growing prevalence of metabolic and age-related bone disorders, our results demonstrate for the first time in translational approaches that GPR40 is a relevant target for the design of new nutritional and therapeutic strategies to counter bone complications. |
