Choline kinase beta is required for normal endochondral bone formation

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. © 2014 Elsevier B.V