title: Inositol polyphosphate 4-phosphatase B as a regulator of bone mass in mice and humans.
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.
authors: Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.
authors: Mathieu
authors: M
authors: Ferron
authors: Maya
authors: M
authors: Boudiffa
authors: Michel
authors: M
authors: Arsenault
authors: Mohamed
authors: M
authors: Rached
authors: Monica
authors: M
authors: Pata
authors: Sylvie
authors: S
authors: Giroux
authors: Latifa
authors: L
authors: Elfassihi
authors: Marina
authors: M
authors: Kisseleva
authors: Philip W
authors: PW
authors: Majerus
authors: François
authors: F
authors: Rousseau
authors: Jean
authors: J
authors: Vacher
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology; D010024:Osteoporosis / Q000209:etiology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050778:NFATC Transcription Factors; D020033:Protein Isoforms; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase; D002118:Calcium