Inpp4b as a regulator of bone mass

Osteoclasts are the major cell type involved in bone resorption. Unbalanced increase of osteoclasts activity decreases bone mass and favors osteoporosis. The authors of this study [1] identified a regulator of osteoclastogenesis, inositol polyphosphate 4-phosphatase type 2 α (Inpp4bα), a member of the PI3 kinase signaling pathway.

This phosphatase was expressed from early osteoclast differentiation to activation stage. Ex vivo expression of Inpp4bα repressed osteoclast differentiation, whereas inactive Inpp4bα mutant increased shape, number and cell differentiation rate. Inpp4bα affected intracellular calcium level that controlled NFATc1 nuclear localization and led to an increase in the expression of osteoclast genes differentiation. In vivo, mice deficient in Inpp4b showed an increased osteoclast differentiation resulting in a decreased bone mass and osteoporosis. The authors identified human INPP4B as a potential important locus for osteoporosis.

This study highlights the role of Inpp4b as a major modulator of osteoclastogenesis which could be involved in bone mineral density variability in mice and humans.

1. Ferron M et al. Cell Metab. 2011;14:466-477.