1α,25 Dihydroxyvitamin D3 Rapidly Regulates the Mouse Osteoprotegerin Gene Through Dual Pathways

Abstract

Taken together with the observation that the OPG promoter has no consensus negative vitamin D-responsive elements, these data suggest that 1 alpha,25(OH)(2)D(3) transrepresses mouse OPG by reducing the proportion of phospho-c-Jun in a JNK-independent manner. Our data indicated that short-term treatment with 1 alpha,25(OH)(2)D(3) effectively downregulated OPG expression both by accelerating the degradation of OPG mRNA and by transrepressing the OPG gene through its AP-1 binding site in the catabolic phase. The OPG gene became insensitive to 1 alpha,25(OH)(2)D(3) treatment, however, and reverted to its steady-state expression level over time, leading to the anabolic phase of the effect of 1 alpha,25(OH)(2)D(3) on bone.