Osteoblast differentiation and control by vitamin D and vitamin D metabolites.

Vitamin D plays a major role in the regulation of mineral homeostasis and affects bone metabolism. Most effects of vitamin D have been attributed to the 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolite. 1,25-(OH)2D3 regulates its own metabolism by mediating the 24-hydroxylase activity, which leads to the degradation of the molecule but intermediate products (24-hydroxylated forms of 25-(OH)D3 and 1,25-(OH)2D3) may be biologically active too. In this review we describe the direct effects of 1,25-(OH)2D3 on osteoblast function (proliferation, apoptosis, expression of specific bone proteins and growth factors) and mineralization. The role of the vitamin D receptor, vitamin D metabolism and the effects on osteoblast gene expression are documented. Vitamin D acts often in interaction with factors. The effects of 1,25-(OH)2D3 on the expression of growth factors and its interaction with growth factors and hormones in the control of osteoblast differentiation are discussed. Finally, the current status of the development of synthetic vitamin D analogs with bone anabolic characteristics for therapeutic application is described.