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Cellular and Molecular Life Sciences

, Volume 68, Issue 2, pp 205–218 | Cite as

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

  • Solmaz Khoshniat
  • Annabelle Bourgine
  • Marion Julien
  • Pierre Weiss
  • Jérôme Guicheux
  • Laurent BeckEmail author
Review

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.

Keywords

Phosphate sensing Phosphate homeostasis Bone mineralization Signaling SLC20a1 SLC20a2 

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

Notes

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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Solmaz Khoshniat
    • 1
    • 2
  • Annabelle Bourgine
    • 1
    • 2
  • Marion Julien
    • 1
    • 2
  • Pierre Weiss
    • 1
    • 2
  • Jérôme Guicheux
    • 1
    • 2
  • Laurent Beck
    • 3
    • 4
    Email author
  1. 1.Group STEP (Skeletal Tissue Engineering and Physiopathology), Centre for Osteoarticular and Dental Tissue Engineering (LIOAD)INSERM, U791NantesFrance
  2. 2.UFR OdontologiePres UNAMNantesFrance
  3. 3.Growth and Signalling Research CenterINSERM, U845ParisFrance
  4. 4.Faculté de Médecine, Centre de Recherche, INSERM U845Université Paris DescartesParisFrance

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