Choline kinase beta is required for normal endochondral bone formation

Biochim Biophys Acta. 2014 Jul;1840(7):2112-22. doi: 10.1016/j.bbagen.2014.03.008. Epub 2014 Mar 14.

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.

General significance: Our data indicate that choline kinase beta plays an important role in endochondral bone formation by modulating growth plate physiology.

Keywords: Choline kinase; Chondrocyte; Endochondral bone formation; Growth plate; Radius; Ulna.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Choline Kinase / genetics*
  • Choline Kinase / metabolism
  • Chondrocytes / enzymology
  • Embryo, Mammalian / enzymology
  • Embryonic Development / genetics
  • Forelimb / embryology
  • Forelimb / enzymology
  • Forelimb / growth & development
  • Growth Plate / enzymology
  • Growth Plate / growth & development*
  • Humans
  • Mice
  • Mice, Knockout
  • Osteogenesis / genetics*
  • Phosphatidylcholines / metabolism

Substances

  • Phosphatidylcholines
  • Choline Kinase