Role of the P2Y13 Receptor in the Differentiation of Bone Marrow Stromal Cells into Osteoblasts and Adipocytes

Authors

  • Galadrielle Biver,

    1. Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium
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  • Ning Wang,

    1. The Mellanby Centre for Bone Research Department of Human Metabolism, The University of Sheffield, Sheffield, United Kingdom
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  • Alison Gartland,

    1. The Mellanby Centre for Bone Research Department of Human Metabolism, The University of Sheffield, Sheffield, United Kingdom
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  • Isabel Orriss,

    1. Department of Cell and Developmental Biology, University College London, London, United Kingdom
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  • Timothy R. Arnett,

    1. Department of Cell and Developmental Biology, University College London, London, United Kingdom
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  • Jean-Marie Boeynaems,

    1. Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium
    2. Department of Medical Chemistry, Erasme Hospital, Brussels, Belgium
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  • Bernard Robaye

    Corresponding author
    1. Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium
    • Ph.D., 10 Rue A. Bolland, Université Libre de, Bruxelles, Gosselies 6041, Belgium. E-mail: brobaye@ulb.ac.be Telephone: +3226509839; Fax: +3226509820

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  • Authors contributions: G.B.: conception and design, collection and assembly data, data analysis and interpretation, and manuscript writing; N.W.: collection and assembly data; A.G. and T.R.A.: data analysis and interpretation; I.O.: collection and assembly data and data analysis and interpretation; J.-M.B.: conception and design, data analysis and interpretation, manuscript writing, and final approval manuscript; B.R.: conception and design, collection and assembly data, data analysis and interpretation, manuscript writing, and final approval manuscript.

Abstract

Accumulating evidence indicates that extracellular nucleotides, signaling through purinergic receptors, play a significant role in bone remodeling. Mesenchymal stem cells (MSCs) express functional P2Y receptors whose expression level is regulated during osteoblast or adipocyte differentiation. P2Y13-deficient mice were previously shown to exhibit a decreased bone turnover associated with a reduction in the number of both osteoblasts and osteoclasts on the bone surfaces. We therefore examined whether P2Y13R activation was involved in the osteogenic differentiation of MSC. Our study demonstrated that ADP stimulation of P2Y13R+/+ (but not P2Y13R-/-) adherent bone marrow stromal cells (BMSCs) increased significantly the formation of alkaline phosphatase-colony-forming units (CFU-ALP) as well as the expression of osteoblastic markers (osterix, alkaline phosphatase, and collagen I) involved in the maturation of preosteoblasts into osteoblasts. The number of CFU-ALP obtained from P2Y13R-/- BMSC and the level of osteoblastic gene expression after osteogenic stimulation were strongly reduced compared to those obtained in wild-type cell cultures. In contrast, when P2Y13R-/- BMSCs were incubated in an adipogenic medium, the number of adipocytes generated and the level of adipogenic gene expression (PPARγ2 and Adipsin) were higher than those obtained in P2Y13R+/+ MSC. Interestingly, we observed a significant increase of the number of bone marrow adipocytes in tibia of P2Y13R-/- mice. In conclusion, our findings indicate that the P2Y13R plays an important role in the balance of osteoblast and adipocyte terminal differentiation of bone marrow progenitors. Therefore, the P2Y13 receptor can be considered as a new pharmacological target for the treatment of bone diseases like osteoporosis. STEM Cells 2013;31:2747–2758

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