Choline Kinase Beta Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity and Low Bone Mass [Cell Biology]

December 1st, 2014 by Kular, J., Tickner, J. C., Pavlos, N. J., Viola, H. M., Abel, T., Lim, B. S., Yang, X., Chen, H., Cook, R., Hool, L. C., Zheng, M. H., Xu, J.

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 beta (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase beta 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 CDP-choline (Cytidine 5-diphosphocholine) in vivo and in vitro, a regimen which 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.