Vitamin D and differentiation of mesenchymal stem cells and osteoblasts
Hans van Leeuwen
Vitamin D is one of the major factors involved in calcium and phosphate homeostasis via actions on intestine, kidney, parathyroid gland, and bone. In addition, vitamin D has effects on various cells and tissues not primarily related to calcium, phosphate and bone metabolism, including the immunesystem, brain, and various cancer cells. Vitamin D deficiency is linked to incidence and progress of various diseases. Currently there is an increase in discussion on the question about vitamin D deficiencies and there is an increasing awareness. The biologically most active form of vitamin D is 1α,25-dihydroxyvitamin D3 (1,25D3). 1,25D3 is synthesized from the parental vitamin D molecule by sequential hydroxylations in the liver (25-hydroxylation) and kidney (1α-hydroxylation).
1,25D3 is involved in bone formation and mineralization and it is used to prevent and treat osteoporosis. These influences on bone can be indirectly established through the control of calcium uptake in the intestine or reabsorption in the kidney. However, direct effects are also likely as the vitamin D receptor is present in osteoblasts. In addition, 1,25D3 can directly affect osteoblasts as shown by stimulating in vitro mineralization in osteoblast cultures and by altering gene regulation. Moreover, we were able to show that osteoblasts themselves can synthesize 1,25D3, emphasizing the importance of local 1,25D3 for osteoblasts. In the current presentation the direct regulation of osteoblast differentiation by vitamin D and interaction with other signaling pathways will be discussed. The effect of vitamin D on composition of the extracellular bone matrix and the impact on mineralization will be presented.