title: 25-Hydroxyvitamin D3induces osteogenic differentiation of human mesenchymal stem cells.
abstract: 25-Hydroxyvitamin D3[25(OH)D3] has recently been found to be an active hormone. Its biological actions are demonstrated in various cell types. 25(OH)D3deficiency results in failure in bone formation and skeletal deformation. Here, we investigated the effect of 25(OH)D3on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We also studied the effect of 1α,25-dihydroxyvitamin D3[1α,25-(OH)2D3], a metabolite of 25(OH)D3. One of the vitamin D responsive genes, 25(OH)D3-24-hydroxylase (cytochrome P450 family 24 subfamily A member 1) mRNA expression is up-regulated by 25(OH)D3at 250-500 nM and by 1α,25-(OH)2D3at 1-10 nM. 25(OH)D3and 1α,25-(OH)2D3at 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)D3and 1α,25-(OH)2D3in a dose-dependent manner. Finally, mineralisation is significantly increased by 25(OH)D3but not by 1α,25-(OH)2D3. Moreover, we found that hMSCs express very low level of 25(OH)D3-1α-hydroxylase (cytochrome P450 family 27 subfamily B member 1), and there is no detectable 1α,25-(OH)2D3product. Taken together, our findings provide evidence that 25(OH)D3at 250-500 nM can induce osteogenic differentiation and that 25(OH)D3has great potential for cell-based bone tissue engineering.
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.|Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Lou
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.|Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Tai Chong
authors.initials: TC
authors.lastname: Toh
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9 #04-11, 2 Medical Drive, Singapore 117597, Singapore.|Mechanobiology Institute, National University of Singapore, T-Laboratories, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Yee Han
authors.initials: YH
authors.lastname: Tee
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9 #04-11, 2 Medical Drive, Singapore 117597, Singapore.|Mechanobiology Institute, National University of Singapore, T-Laboratories, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, National University of Singapore, #05-01, 28 Medical Drive, Singapore 117576, Singapore.|Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore 138602, Singapore.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.|Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, North of Guangzhou Dadao, Guangzhou 510515, China.
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002112:Calcifediol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: C506895:SPP1 protein, human; D014815:Vitamins; C118756:dihydroxy-vitamin D3; D015675:Osteocalcin; D053495:Osteopontin; D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D000469:Alkaline Phosphatase; D002112:Calcifediol