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GPR40, a free fatty acid receptor, differentially impacts osteoblast behavior depending on differentiation stage and environment

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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.

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Abbreviations

ALP:

Alkaline phosphatase

GPR40:

G-protein receptor 40

KO:

Knock-out

NF-κB:

Nuclear factor kappa B

OPG:

Osteoprotegerin

OVX:

Ovariectomized

RANKL:

Receptor activator of NF-κB ligand

Runx2:

Runt related transcription factor 2

SH:

Sham-operated

TLDA:

Taqman low-density arrays

TZD:

Thiazolidinediones

WT:

Wild-type

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Acknowledgments

GPR40−/− mice were obtained from Vincent Poitout, Thierry Alquier and Amgen Inc. Thousand Oaks, CA, USA. We also thank Emilie Daudet for her technical assistance.

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Authors and Affiliations

  1. INRA, UMR 1019, UNH, CRNH Auvergne, 63009, Clermont-Ferrand, France

    Claire Philippe, Fabien Wauquier, Véronique Coxam & Yohann Wittrant

  2. INRA, UMR 1019, Plateforme d’Exploration du Métabolisme, UNH, 63000, Clermont-Ferrand, France

    Bernard Lyan

  3. Clermont Université, Université d’Auvergne, Unité de Nutrition Humaine, BP 10448, 63000, Clermont-Ferrand, France

    Claire Philippe, Fabien Wauquier, Bernard Lyan, Véronique Coxam & Yohann Wittrant

  4. Equipe Alimentation, Squelette Et Métabolismes, Saint Genès-Champanelle, France

    Claire Philippe, Fabien Wauquier, Véronique Coxam & Yohann Wittrant

  5. UMR1019 INRA Université d’Auvergne – Unité de Nutrition Humaine, 63122, Saint Genès-Champanelle, France

    Yohann Wittrant

Authors
  1. Claire Philippe
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  2. Fabien Wauquier
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  3. Bernard Lyan
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Correspondence to Yohann Wittrant.

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Philippe, C., Wauquier, F., Lyan, B. et al. GPR40, a free fatty acid receptor, differentially impacts osteoblast behavior depending on differentiation stage and environment. Mol Cell Biochem 412, 197–208 (2016). https://doi.org/10.1007/s11010-015-2626-5

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  • DOI: https://doi.org/10.1007/s11010-015-2626-5

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