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.

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