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The emergence of phosphate as a specific signaling molecule in bone and other cell types in mammals

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Abstract

Although considerable advances in our understanding of the mechanisms of phosphate homeostasis and skeleton mineralization have recently been made, little is known about the initial events involving the detection of changes in the phosphate serum concentrations and the subsequent downstream regulation cascade. Recent data has strengthened a long-established hypothesis that a phosphate-sensing mechanism may be present in various organs. Such a phosphate sensor would detect changes in serum or local phosphate concentration and would inform the body, the local environment, or the individual cell. This suggests that phosphate in itself could represent a signal regulating multiple factors necessary for diverse biological processes such as bone or vascular calcification. This review summarizes findings supporting the possibility that phosphate represents a signaling molecule, particularly in bone and cartilage, but also in other tissues. The involvement of various signaling pathways (ERK1/2), transcription factors (Fra-1, Runx2) and phosphate transporters (PiT1, PiT2) is discussed.

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Abbreviations

1α,25(OH)2D3 :

1α,25-dihydroxyvitamin D

ALP:

Alkaline phosphatase

Pi:

Inorganic phosphate

IGF-1:

Insulin growth factor-1

ESRD:

End-stage renal disease

FGF-23:

Fibroblast growth factor 23

HSMC:

Human aortic smooth muscle cell

MGP:

Matrix gla protein

PTH:

Parathyroid hormone

PFA:

Phosphonoformic acid

RANKL:

Receptor activator of nuclear factor kappa B (NF-κB) (RANK) ligand

VSMC:

Vascular smooth muscle cell

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Acknowledgments

The authors gratefully acknowledge Joanna Ashton-Chess for critical reading of the manuscript. This work was partially supported by grants from INSERM, ANR (PHYSIOPATH ANR-07-PHYSIO-017-01), La Fondation pour la Recherche Médicale (AAP “Vieillissement ostéoarticulaire”), BIOREGOS and Région des Pays de la Loire. Marion Julien received a fellowship from INSERM/Région des Pays de la Loire and La Fondation pour la Recherche Médicale, Solmaz Khoshniat from the French Ministry of Research and la Fondation pour la Recherche Médicale and Annabelle Bourgine from INSERM/Région des Pays de la Loire.

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Authors and Affiliations

  1. Group STEP (Skeletal Tissue Engineering and Physiopathology), Centre for Osteoarticular and Dental Tissue Engineering (LIOAD), INSERM, U791, 44042, Nantes, France

    Solmaz Khoshniat, Annabelle Bourgine, Marion Julien, Pierre Weiss & Jérôme Guicheux

  2. UFR Odontologie, Pres UNAM, 44042, Nantes, France

    Solmaz Khoshniat, Annabelle Bourgine, Marion Julien, Pierre Weiss & Jérôme Guicheux

  3. Growth and Signalling Research Center, INSERM, U845, 75015, Paris, France

    Laurent Beck

  4. Faculté de Médecine, Centre de Recherche, INSERM U845, Université Paris Descartes, 156 Rue de Vaugirard, 75015, Paris, France

    Laurent Beck

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  1. Solmaz Khoshniat
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  3. Marion Julien
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Correspondence to Laurent Beck.

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J. Guicheux and L. Beck contributed equally to this work.

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Khoshniat, S., Bourgine, A., Julien, M. et al. The emergence of phosphate as a specific signaling molecule in bone and other cell types in mammals. Cell. Mol. Life Sci. 68, 205–218 (2011). https://doi.org/10.1007/s00018-010-0527-z

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