BoneKEy Reports | BoneKEy Watch

GPR40, a free fatty acid receptor, inhibits osteoclast differentiation and spares bone

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DOI:10.1038/bonekey.2013.75

MicroCT scanning was used to show that mice lacking the ability to express the gene that encodes G-coupled protein receptor 40 (GPR40), a free fatty acid receptor, had lower bone mineral density and reduced bone volume and exhibited changes in their bone microarchitecture.

In vitro techniques showed that osteoclasts from wild-type mice expressed GPR40 and then revealed that GW9508, a GPR40 agonist, was able to inhibit RANKL-dependent osteoclast differentiation via inhibition of the NF-κB pathway. Mice lacking the ability to express GPR40 showed further bone loss after ovariectomy, but ovariectomized wild-type mice treated with GW9508 did not. Comparison of wild-type treated and untreated mice showed that osteoclast marker expression was reduced in the treated group but osteoprotegerin expression did not fall, confirming that osteoclast differentiation was reduced via a GPR40-dependent mechanism.

Editor’s comment: Lipid intake has generally been associated with decreased bone mass. Activation of peroxisome proliferator-activated receptor gamma, leading to adipogenesis at the expense of osteoblastogenesis from bone marrow precursor cells, has been suggested as a major mechanism implicated in this phenomenon. However, this paper shows that fatty acids could do the opposite; they may help to protect bone by activating the free fatty acid receptor GPR40, which inhibits RANKL-induced osteoclastogenesis.

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