TGF-beta and calcitriol

Vitamin D3 and transforming growth factor-beta (TGF-beta) are molecules from unrelated families that share identical actions on cell growth and differentiation. The active metabolite of vitamin D3, calcitriol (1alpha,25-dihydroxyvitamin D3), induces an inhibitory effect on the growth of various cell types, and the expression of different markers of cell differentiation. As the receptor of vitamin D3 is ubiquitous, these effects are widespread in the organism. TGF-beta is a growth factor produced by many cell types, and is a known inhibitor of the proliferation of epithelial cells. Because of the similarity in their actions, many studies have been aimed at defining some interactions between the two substances. The purpose of this article is to illustrate the nature of the interactions, and two examples are developed. In normal or transformed epithelial cells, it has been demonstrated that the inhibitory effect of calcitriol on cell growth could be related to an induction of TGF-beta synthesis, and of a paracrine/autocrine loop. In bone, where both compounds play a very important role on the mechanisms controlling bone formation and remodeling, the interplay is more complex, and even includes the receptors of the two substances. Interest in this topic is growing and will surely lead to the establishment of new links between those two compounds.