Lithocholate-A promising non-calcaemic calcitriol surrogate for promoting human osteoblast maturation upon biomaterials

Mansell, Jason Peter; Shorez, David; Farrar, David; Nowghani, Maryam

Abstract

Background and aims: Calcitriol, an active vitamin D metabolite, has a limited application in bone repair because of its undesirable hypercalcaemic action. However it has emerged that lithocholic acid (LCA) is a non-calcaemic vitamin D receptor ligand but whether this steroid can support osteoblast maturation has not been reported. Using the human osteoblast cell line, MG63, we explored the potential of LCA and LCA derivatives to secure osteoblast maturation. Results: The co-stimulation of cells with LCA, LCA acetate or LCA acetate methyl ester (0.5-5 μM) and lysophosphatidic acid (LPA, 20 μM) resulted in clear, synergistic increases in MG63 maturation that was both time and dose dependent. Cells grown upon both titanium and hydroxyapatite, two widely used implant materials, responded well to co-treatment with LCA acetate (5 μM) and LPA (20 μM) as demonstrated by stark, synergistic increases in ALP activity. Evidence of activator protein-1 (AP-1) stimulation by LCA acetate (30 μM) was demonstrated using an AP-1 luciferase reporter assay. Synergistic increases in ALP activity, and therefore osteoblast maturation, were observed for MG63 cells co-stimulated with LCA acetate (5 μM) and either epidermal growth factor (10 ng/ml) or transforming growth factor-β (10 ng/ml). Ligands acting on either the farnesoid X receptor or pregnane X receptor could not substitute for the action of LCA acetate on MG63 maturation. Conclusions: Lithocholate is able to act as a calcitriol surrogate in generating mature osteoblasts. Given that LCA is non-calcaemic it is likely to find an application in bone repair/regeneration by aiding matrix calcification at implant sites. © 2009 Elsevier Inc. All rights reserved.

Citation

Mansell, J. P., Shorez, D., Farrar, D., & Nowghani, M. (2009). Lithocholate-A promising non-calcaemic calcitriol surrogate for promoting human osteoblast maturation upon biomaterials. Steroids, 74(12), 963-970. https://doi.org/10.1016/j.steroids.2009.07.005

• Journal Article Type: Article
• Publication Date: Nov 4, 2009
• Journal: Steroids
• Print ISSN: 0039-128X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 12
• Pages: 963-970
• DOI: https://doi.org/10.1016/j.steroids.2009.07.005
• Keywords: osteoblasts, lithocholic acid, lysophosphatidic acid, ; biomaterials, differentiation
• Public URL: https://uwe-repository.worktribe.com/output/1004141
• Publisher URL: http://dx.doi.org/10.1016/j.steroids.2009.07.005