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24,25-Dihydroxyvitamin D3 cooperates with a stable, fluoromethylene LPA receptor agonist to secure human (MG63) osteoblast maturation

Lancaster, Sarah Tamar; Blackburn, Julia; Blom, Ashley; Makishima, Makoto; Mansell, Jason; Ishizawa, Michiyasu

Authors

Sarah Tamar Lancaster

Julia Blackburn

Ashley Blom

Makoto Makishima

Jason Mansell Jason.Mansell@uwe.ac.uk
Associate Professor in Biomedical Sciences

Michiyasu Ishizawa



Abstract

Vitamin D receptor (VDR) agonists supporting human osteoblast (hOB) differentiation in the absence of bone resorption are attractive agents in a bone regenerative setting. One potential candidate fulfilling these roles is 24,25-dihydroxy vitamin D3 (24,25D). Over forty years ago it was reported that supraphysiological levels of 24,25D could stimulate intestinal calcium uptake and aid bone repair without causing bone calcium mobilisation. VDR agonists co-operate with certain growth factors to enhance hOB differentiation but whether 24,25D might act similarly in promoting cellular maturation has not been described. Given our discovery that lysophosphatidic acid (LPA) co-operated with VDR agonists to enhance hOB maturation, we co-treated MG63 hOBs with 24,25D and a phosphatase-resistant LPA analog. In isolation 24,25D inhibited proliferation and stimulated osteocalcin expression. When co-administered with the LPA analog there were synergistic increases in alkaline phosphatase (ALP). These are encouraging findings which may help realise the future application of 24,25D in promoting osseous repair. © 2014 Elsevier Inc. All rights reserved.

Journal Article Type Article
Publication Date Jan 1, 2014
Journal Steroids
Print ISSN 0039-128X
Electronic ISSN 1878-5867
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 83
Pages 52-61
APA6 Citation Mansell, J. P., Lancaster, S. T., Lancaster, S., Blackburn, J., Blom, A., Makishima, M., …Mansell, J. (2014). 24,25-Dihydroxyvitamin D3 cooperates with a stable, fluoromethylene LPA receptor agonist to secure human (MG63) osteoblast maturation. Steroids, 83, 52-61. https://doi.org/10.1016/j.steroids.2014.01.010
DOI https://doi.org/10.1016/j.steroids.2014.01.010
Keywords human osteoblasts, 24,25-dihydroxy vitamin D3, lysophosphatidic acid, differentiation, alkaline phosphatase, osteocalcin
Publisher URL http://dx.doi.org/10.1016/j.steroids.2014.01.010

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