1,25-Dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells

Rat osteosarcoma cells respond to 1,25-dihydroxyvitamin D3 with a 6-fold increase in intracellular and secreted levels of the vitamin K-dependent protein of bone (BGP). The rise in intracellular BGP levels is half-maximal at 6.6 h and precedes the rise in medium BGP levels by 6 h, a time course which is consistent with the postulated steroid hormone action of 1,25-dihydroxyvitamin D3. This effect is achieved by physiological levels of 1,25-dihydroxyvitamin D3, with half of the maximal response at a vitamin concentration of 0.04 ng/ml. The specificity of this effect for BGP is demonstrated by the absence of a 1,25-dihydroxyvitamin D3 effect on total protein synthesis by these cells. To our knowledge, BGP is the first example of a bone protein whose rate of synthesis is dramatically and specifically increased by physiological levels of 1,25-dihydroxyvitamin D3. The possible functions of BGP in the biological actions of 1,25-dihydroxyvitamin D3 on bone are discussed.