Cited by 57Vitamin D Research StudiesBone Metabolism and DiseasesBone health and osteoporosis research

The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation

Turner, Andrew G., Hanrath, Maarten A., Morris, Howard A., Atkins, Gerald J., Anderson, Paul H.·2014·The Journal of Steroid Biochemistry and Molecular Biology

Abstract

Maintenance of an adequate vitamin D status, as indicated by the level of circulating 25-hydroxyvitamin D (25(OH)D), is associated with higher bone mass and decreased risk of fracture. However, the molecular actions of vitamin D hormone (1,25(OH)2D3) in bone are complex, and include stimulation of osteoclastogenesis via RANK-ligand up-regulation, as well as the inhibition of mineralisation. We hypothesise that these divergent data may be reconciled by autocrine actions of 1,25(OH)2D3 which effect skeletal maintenance, as opposed to endocrine 1,25(OH)2D3 which acts to maintain serum calcium homeostasis. We have previously described local metabolism of 1,25(OH)2D3 within osteoblasts, with effects on gene expression and cell function. The aim of the current study was to investigate potential autocrine actions of 1,25(OH)2D3 within cells that exhibit osteocyte-like properties. Late osteoblastic MLO-A5 cells were cultured in the presence of 25(OH)D for 9 days with gene expression analysed pre- and post-mineralisation. Gene expression analysis revealed maturation within this time frame to an osteocyte-like stage, evidenced by increased Dmp1 and Phex mRNA expression. Expression of Cyp27b1 in 25(OH)D treated MLO-A5 cells was associated with elevated media levels of 1,25(OH)2D3 (p<0.05), induction of Cyp24a1 (p<0.001) and elevated ratios of Opg:Rankl mRNA (p<0.01). Chronic 25(OH)D exposure also increased osteocalcin mRNA in MLO-A5 cells, which contrasted with the dose-dependent inhibition of osteocalcin mRNA observed with acute treatment in MLO-Y4 cells (p<0.01). Treatment of MLO-Y4 cells with 25(OH)D also inhibited Phex mRNA expression (p<0.05), whilst Enpp1 gene expression was induced (p<0.01). Overall, the current study demonstrates that osteocyte-like cells convert physiological levels of 25(OH)D to 1,25(OH)2D3, with changes in gene expression that are consistent with increased osteocyte maturation. Although the physiological role of local metabolism of 1,25(OH)2D3 within osteocytes requires further investigation, the abundance and diverse functions of this cell type within bone underscore its potential importance. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

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Crossref · 10.1016/j.jsbmb.2013.10.003

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  • In addition to its systemic effects, 1,25(OH)2D3 binds to VDR in osteocytes in an autocrine manner, and as they mature, osteocytes acquire the capacity to convert physiological levels of 25(OH)D to 1,25(OH)2D3.

    “In addition to its systemic effects, 1,25(OH)2D3 binds to VDR in osteocytes in an autocrine manner, and as they mature, osteocytes acquire the capacity to convert physiological levels of 25(OH)D to 1,25(OH)2D3.99”

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Authors
Turner, A. G., Hanrath, M. A., Morris, H. A., Atkins, G. J., & Anderson, P. H.
Affiliations
  • University of South Australia (AU)
  • Utrecht University (NL)
  • The University of Adelaide (AU)
Corresponding author
Turner, Andrew G.
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2014-10
Volume
144
Pages
114-118
ISSN
0960-0760 (ISSN-L)
OpenAlex
W1988986529
Cited by
57
References
22
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 10 · 2014: 2
FWCI
3.99
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, autocrine signaling, osteogenic differentiation, MLO-Y4 cells, CYP27B1, CYP24A1, PHEX, ENPP1, DMP1, osteocalcin, RANKL/OPG ratio, bone mineralization, osteoclastogenesis, vitamin D receptor
MeSH terms
Animals, Calcitriol, Cell Differentiation, Humans, Osteoblasts, Osteocytes, Vitamins

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