| First Author | Kular J | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 3 | Pages | 1729-42 |
| PubMed ID | 25451916 | Mgi Jnum | J:237443 |
| Mgi Id | MGI:5812753 | Doi | 10.1074/jbc.M114.567966 |
| Citation | Kular J, et al. (2015) Choline kinase beta mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass. J Biol Chem 290(3):1729-42 |
| abstractText | 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 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. |
