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    Cell Metab. 2011 Oct 5;14(4):466-77.

    Inositol polyphosphate 4-phosphatase B as a regulator of bone mass in mice and humans.

    Ferron M, Boudiffa M, Arsenault M, Rached M, Pata M, Giroux S, Elfassihi L, Kisseleva M, Majerus PW, Rousseau F, Vacher J.

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    Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.

    Abstract

    Osteoporosis is a multifactorial genetic disease characterized by reduction of bone mass due to dysregulation of osteoclast differentiation or maturation. Herein, we identified a regulator of osteoclastogenesis, the murine homolog of inositol polyphosphate 4-phosphatase type IIα (Inpp4bα). Expression of Inpp4bα is detected from early osteoclast differentiation to activation stage. Targeted expression of native Inpp4bα ex vivo repressed whereas phosphatase-inactive Inpp4bα stimulated osteoclast differentiation. Inpp4bα acts on intracellular calcium level that modulates NFATc1 nuclear translocation and activation. In vivo mice deficient in Inpp4b displayed increased osteoclast differentiation rate and potential resulting in decreased bone mass and osteoporosis. Importantly, INPP4B in human was identified as a susceptibility locus for osteoporosis. This study defined Inpp4b as a major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density in mice and humans.

    Copyright © 2011 Elsevier Inc. All rights reserved.

    PMID:
    21982707
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC3204353
    [Available on 2012/10/5]

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