title: Choline kinase β mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass.
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.
authors.affiliation: From the School of Pathology and Laboratory Medicine.
authors.forename: Jasreen
authors.initials: J
authors.lastname: Kular
authors.affiliation: From the School of Pathology and Laboratory Medicine.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Tickner
authors.affiliation: Centre for Orthopaedic Research, School of Surgery.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Pavlos
authors.affiliation: School of Anatomy, Physiology and Human Biology, and.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Viola
authors.affiliation: Centre for Microscopy, Characterization and Analysis, University of Western Australia, Nedlands 6009, Western Australia, Australia and.
authors.forename: Tamara
authors.initials: T
authors.lastname: Abel
authors.affiliation: From the School of Pathology and Laboratory Medicine.
authors.forename: Bay Sie
authors.initials: BS
authors.lastname: Lim
authors.affiliation: the Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou 510182, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.affiliation: the Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou 510182, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Chen
authors.affiliation: From the School of Pathology and Laboratory Medicine.
authors.forename: Robert
authors.initials: R
authors.lastname: Cook
authors.affiliation: School of Anatomy, Physiology and Human Biology, and.
authors.forename: Livia C
authors.initials: LC
authors.lastname: Hool
authors.affiliation: Centre for Orthopaedic Research, School of Surgery.
authors.forename: Ming Hao
authors.initials: MH
authors.lastname: Zheng
authors.affiliation: From the School of Pathology and Laboratory Medicine, jiake.xu@uwa.edu.au.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002797:Choline Kinase / Q000235:genetics*; D006706:Homeostasis; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D010767:Phosphorylcholine / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D010767:Phosphorylcholine; D002797:Choline Kinase; D002118:Calcium
keywords: Bone; Choline Kinase-β; Mutagenesis; Osteoblast; Osteoclast; Osteoporosis