Active vitamin D and vitamin D analogs stimulate fibroblast growth factor 23 production in osteocyte-like cells via the vitamin D receptor
Abstract
Osteocytes play an important role in the regulation of serum phosphorus by producing fibroblast growth factor 23 (FGF23). FGF23 production is stimulated by 1α,25-dihydroxyvitamin D in osteocytes. However, it is unclear whether vitamin D induces FGF23 production in osteocytes directly. Therefore, we investigated vitamin D-induced FGF23 production in osteocyte-like cells derived from MC3T3-E1 osteocyte progenitor cells. We also investigated differences in the induction of FGF23 by 1α,25-dihydroxyvitamin D and various vitamin D analogs. MC3T3-E1 cells were differentiated into osteocyte-like cells (MCT3-E1-OLCs) by treatment with various agents including β-glycerophosphate and ascorbic acid. MCT3-E1-OLCs were stimulated with 1α,25-dihydroxyvitamin D 3 and subsequent FGF23 gene expression was 2631 ± 605 times higher compared with untreated cells. The expression of FGF23 in MCT3-E1-OLCs transfected with a knockdown sequence against vitamin D receptor (VDR) was significantly decreased compared with that in cells transfected with the control vector. Therefore, the induction of FGF23 in osteocytes by vitamin D may be primarily mediated via VDR. The potential of 25(OH)vitamin D 3, paricalcitol, and maxacalcitol to induce FGF23 production was almost the same as that of 1α,25-dihydroxyvitamin D 3. However, falecalcitriol and eldecalcitol demonstrated a reduced potential to induce FGF23 compared with 1α,25-dihydroxyvitamin D 3. Our results demonstrate that FGF23 induction is different among the analogs of 1α,25-dihydroxyvitamin D 3. Therefore, an appropriate vitamin D analog should be chosen for each patient with mineral and bone disorder, considering its effect on FGF23 production.
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1,25(OH)2D3 stimulates the production of fibroblast factor 23 (FGF23) in osteocyte-like cells.
“recent observations have pointed out that 1,25(OH)2D3 a) stimulates the production of fibroblast factor 23 (FGF23) in osteocyte-like cells;100”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [100]
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- Authors
- Yashiro, M., Ohya, M., Mima, T., Nakashima, Y., Kawakami, K., Yamamoto, S., Kobayashi, S., Yano, T., Tanaka, Y., Sonou, T., Tatsuta, K., Negi, S., & Shigematsu, T.
- Affiliations
- Wakayama Medical University (JP)
- Corresponding author
- Mima, Toru
- Venue
- Journal of Pharmaceutical and Biomedical Analysis
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 182
- Pages
- 113139
- ISSN
- 0731-7085 (ISSN-L)
- OpenAlex
- W3003409864
- Cited by
- 18
- References
- 20
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical and Biomedical Analysis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Grant-in-Aid for Scientific Research (16K09652)
- Wakayama Kidney Foundation
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- fibroblast growth factor 23, vitamin D receptor, osteocytes, 1,25-dihydroxyvitamin D3, vitamin D analogs, paricalcitol, maxacalcitol, eldecalcitol, 25-hydroxyvitamin D3, osteocyte-like cells, MC3T3-E1 cells, mineral and bone disorder
- MeSH terms
- Fibroblast Growth Factor-23, Animals, Cell Differentiation, Cell Line, Fibroblast Growth Factors, Gene Expression Regulation, Osteocytes, Vitamin D, Receptors, Calcitriol, Mice, Gene Knockdown Techniques
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