title: Promoting effect of 1,25(OH)2 vitamin D3 in osteogenic differentiation from induced pluripotent stem cells to osteocyte-like cells.
abstract: We recently reported a new method to purify the induced pluripotent stem (iPS)-derived osteoprogenitors (iPSop). In this paper, we optimized the procedure and characterized cells at each process step. We observed that 10 days of treatment with FGF-2, IGF-1 and TGF-β (FIT) resulted in early-phase osteoblasts and 14 days of treatment resulted in late-phase osteoblasts. We found that treatment with 1,25(OH)2 vitamin D3 increased expression of osteocalcin and decreased expression of tissue-non-specific alkaline phosphatase and runt-related transcription factor 2 (RUNX2) in iPSop-day14 cells (cells treated with FIT for 14 days). Therefore, iPSop-day14 cells were promoted to mature osteoblasts by 1,25(OH)2 vitamin D3 treatment. In addition, we found that 1,25(OH)2 vitamin D3 treatment for 14 days enhanced not only mineralization but also expression of osteocyte markers, including dentin matrix protein-1 and fibroblast growth factor-23, in iPSop cells. Therefore, 1,25(OH)2 vitamin D3 is a potent promoter of osteoblast-osteocyte transition. The results of this study suggest that it is possible to evaluate both early- and late-phase osteoblasts and to apply cells to drug screening for anabolic drugs that stimulate bone formation.
authors: Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kato
authors: Department of Biochemistry, Tokyo Dental College, Tokyo, Japan.
authors: Hiromi
authors: H
authors: Ochiai-Shino
authors: Department of Biochemistry, Tokyo Dental College, Tokyo, Japan.
authors: Shoko
authors: S
authors: Onodera
authors: Department of Biochemistry, Tokyo Dental College, Tokyo, Japan.
authors: Akiko
authors: A
authors: Saito
authors: Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Tokyo, Japan.
authors: Takahiko
authors: T
authors: Shibahara
authors: Department of Biochemistry, Tokyo Dental College, Tokyo, Japan tazuma@tdc.ac.jp.
authors: Toshifumi
authors: T
authors: Azuma
mesh_terms: D000818:Animals; D015415:Biomarkers; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D058732:Embryoid Bodies / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics
chemical_list: D015415:Biomarkers; D002117:Calcitriol
keywords: drug assessment; induced pluripotent stem cells; osteoblasts; osteocytes; vitamin D
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