title: Choline kinase beta is required for normal endochondral bone formation.
abstract: BACKGROUND
  Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb(-/-) mice display neonatal forelimb bone deformations.
  
  
  METHODS
  To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb(-/-) mice.
  
  
  RESULTS
  The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb(-/-) mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation of chondrocytes of Chkb(-/-) mice was impaired, as was chondrocyte proliferation and expression of matrix metalloproteinases 9 and 13. In chondrocytes from Chkb(-/-) mice, phosphatidylcholine was slightly lower than in WT mice whereas the amount of phosphocholine was decreased by approximately 75%. In addition, the radius and ulna from Chkb(-/-) mice contained fewer osteoclasts along the cartilage/bone interface.
  
  
  CONCLUSIONS
  Chkb has a critical role in the normal embryogenic formation of the radius and ulna in mice.
  
  
  CONCLUSIONS
  Our data indicate that choline kinase beta plays an important role in endochondral bone formation by modulating growth plate physiology.
authors.affiliation: Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2 Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2 Canada.
authors.forename: Gengshu
authors.initials: G
authors.lastname: Wu
authors.affiliation: University of Maine, Orono, ME, USA.
authors.forename: Roger B
authors.initials: RB
authors.lastname: Sher
authors.affiliation: Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Khavandgar
authors.affiliation: Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2 Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Hermansson
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Cox
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
authors.affiliation: Faculty of Dentistry, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Monzur
authors.initials: M
authors.lastname: Murshed
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Beier
authors.affiliation: Group on the Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2 Canada. Electronic address: dennis.vance@ualberta.ca.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Vance
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002797:Choline Kinase / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000201:enzymology; D004622:Embryo, Mammalian / Q000201:enzymology; D047108:Embryonic Development / Q000235:genetics; D005552:Forelimb / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D006132:Growth Plate / Q000201:enzymology / Q000254:growth & development*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics*; D010713:Phosphatidylcholines / Q000378:metabolism
chemical_list: D010713:Phosphatidylcholines; D002797:Choline Kinase
keywords: Choline kinase; Chondrocyte; Endochondral bone formation; Growth plate; Radius; Ulna