Skip to main content

ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1392418
This article is part of the Research Topic Bone Cell Differentiation in Health and Disease, Volume II View all 6 articles

The short-chain fatty acid receptors Gpr41/43 regulate bone mass by promoting adipogenic differentiation of mesenchymal stem cells

Provisionally accepted
Friederike Behler-Janbeck Friederike Behler-Janbeck 1*Anke Baranowsky Anke Baranowsky 2Timur Yorgan Timur Yorgan 3Michelle Y. Jaeckstein Michelle Y. Jaeckstein 1Anna Worthmann Anna Worthmann 1Marceline M. Fuh Marceline M. Fuh 1Gisa Tiegs Gisa Tiegs 4Michael Amling Michael Amling 3Thorsten Schinke Thorsten Schinke 3Joerg Heeren Joerg Heeren 1
  • 1 Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • 2 Department of Trauma and Orthopaedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 3 Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 4 Institute for Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany

The final, formatted version of the article will be published soon.

    Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate. SCFAs exert various metabolic functions, which in part can be explained by activation of G protein-coupled receptors (Gpr) 41 and 43. However, the potential relevance of a SCFA-Gpr41/43 signaling axis for bone metabolism has not been established. The aim of our study is to investigate the role of Gpr41/43 in bone metabolism and osteogenic differentiation of mesenchymal stem cells. For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. In addition, we isolated bone marrow derived mesenchymal stem cells from WT and Gpr41/43 dKO mice and differentiated them into osteoblasts in the absence or presence of acetate. MicroCT scanning of femoral bones of Gpr41/43 dKO mice revealed a significant increase of trabecular bone volume and trabecular compared to WT controls. Treatment of WT bone marrow-derived osteoblasts with acetate resulted in decreased mineralization and substantial downregulation of bone formation markers such as Phex, Ptgs2 and Col1a1. Notably, this effect was strongly attenuated in differentiated osteoblasts lacking Gpr41/43. Inversely, acetate supplementation resulted in higher levels of adipocyte marker genes including Pparg, Lpl and Adipoq in bone marrow-derived cells from WT mice, an effect blunted in differentiated cells isolated from Gpr41/43 dKO mice. Overall, these data indicate that acetate regulates bone architecture via SCFA-Gpr41/43 signaling by modulating the osteogenic versus adipogenic differentiation of mesenchymal stem cells.

    Keywords: G protein-coupled receptors, GPR41/43, Short-chain fatty acids (SCFAs), acetate, Osteoblasts, Bone formation, Adipogenesis

    Received: 27 Feb 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Behler-Janbeck, Baranowsky, Yorgan, Jaeckstein, Worthmann, Fuh, Tiegs, Amling, Schinke and Heeren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Friederike Behler-Janbeck, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Hamburg, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.