Work

Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass

Year: 2014

Type: article

Abstract: The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5′-diphosphocholine in vivo and in vitro , a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis.Bone homeostasis requires constant remodeling by bone-resorbing osteoclasts and bone-forming osteoblasts. Results Choline kinase β (CHKB)-deficient mice have reduced bone mass, increased osteoclast number, and impaired osteoblast function. Conclusion CHKB activity controls bone homeostasis via regulation of osteoclasts and osteoblasts. Significance This is the first report implicating a role for CHKB in bone homeostasis.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m114.567966