title: GPR40, a free fatty acid receptor, differentially impacts osteoblast behavior depending on differentiation stage and environment.
abstract: GPR40 is a free fatty acid receptor that has been recently shown to impact bone remodeling. This receptor protects skeleton by inhibiting bone resorbing osteoclast differentiation. Consistent with GPR40 expression on bone forming cells, we assumed that this receptor may also influence osteoblast activity. To further investigate this hypothesis, biological effects of GW9508, a synthetic agonist for GPR40, was first tested on osteoblast differentiation parameters. Assays were performed in two different cell models: the MC3T3-E1 osteoblastic cell line and primary bone marrow cultures extracted from wild-type and GPR40 knock-out mice. Both models showed a dual role of GPR40 on osteoblasts. Although receptor stimulation induced early stimulation of differentiation marker expression, it finally led to inhibition of mineralization process during late differentiation stages. To further elucidate this discrepancy, mice were ovariectomized to induce bone loss and received GPR40 agonist by gavage. Data revealed a weak influence of GPR40 agonist on osteoblast markers expression. Nevertheless, a significant increase in OPG expression was observed upon GW9508 treatment that contribute to explain the GPR40-related osteoporosis prevention. To conclude, our results confirm the relevance of this new opportunity in the management of bone loss.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63009, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France.|Equipe Alimentation, Squelette Et Métabolismes, Saint Genès-Champanelle, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Philippe
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63009, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France.|Equipe Alimentation, Squelette Et Métabolismes, Saint Genès-Champanelle, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Wauquier
authors.affiliation: INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lyan
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63009, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France.|Equipe Alimentation, Squelette Et Métabolismes, Saint Genès-Champanelle, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Coxam
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63009, Clermont-Ferrand, France. yohann.wittrant@clermont.inra.fr.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France. yohann.wittrant@clermont.inra.fr.|Equipe Alimentation, Squelette Et Métabolismes, Saint Genès-Champanelle, France. yohann.wittrant@clermont.inra.fr.|UMR1019 INRA Université d'Auvergne - Unité de Nutrition Humaine, 63122, Saint Genès-Champanelle, France. yohann.wittrant@clermont.inra.fr.
authors.forename: Yohann
authors.identifier: http://orcid.org/0000-0003-3811-8859
authors.initials: Y
authors.lastname: Wittrant
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000502:physiology*
chemical_list: C473036:Ffar1 protein, mouse; C515630:GW9508; D008744:Methylamines; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D000469:Alkaline Phosphatase
keywords: Cell differentiation; Fatty acids; GPR40; Nutrition; Osteoblast; Osteoporosis