25-Hydroxyvitamin D-3 induces osteogenic differentiation of human mesenchymal stem cells

Abstract

25-Hydroxyvitamin D-3 [25(OH)D-3] has recently been found to be an active hormone. Its biological actions are demonstrated in various cell types. 25(OH)D-3 deficiency results in failure in bone formation and skeletal deformation. Here, we investigated the effect of 25(OH)D-3 on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We also studied the effect of 1 alpha, 25-dihydroxyvitamin D-3[1 alpha,25-(OH)(2)D-3], a metabolite of 25(OH)D-3. One of the vitamin D responsive genes, 25(OH)D-3-24-hydroxylase (cytochrome P450 family 24 subfamily A member 1) mRNA expression is up-regulated by 25(OH)D-3 at 250-500 nM and by 1 alpha, 25-(OH)(2)D-3 at 1-10 nM. 25(OH)D-3 and 1 alpha, 25-(OH)(2)D-3 at a time-dependent manner alter cell morphology towards osteoblast-associated characteristics. The osteogenic markers, alkaline phosphatase, secreted phosphoprotein 1 (osteopontin), and bone gamma-carboxyglutamate protein (osteocalcin) are increased by 25(OH)D-3 and 1 alpha,25-(OH)(2)D-3 in a dose-dependent manner. Finally, mineralisation is significantly increased by 25(OH)D-3 but not by 1 alpha, 25-(OH)(2)D-3. Moreover, we found that hMSCs express very low level of 25(OH)D-3-1 alpha-hydroxylase (cytochrome P450 family 27 subfamily B member 1), and there is no detectable 1 alpha, 25-(OH)(2)D-3 product. Taken together, our findings provide evidence that 25(OH)D-3 at 250-500 nM can induce osteogenic differentiation and that 25(OH)D-3 has great potential for cell-based bone tissue engineering.Peer reviewe