non-calcaemic Lithocholic acid acetate promotes osteoblast maturation
Kofi
Lithocholate--a promising non-calcaemic calcitriol surrogate for
promoting human osteoblast maturation upon biomaterials.
Mansell JP, Shorez D, Farrar D, Nowghani M.
Department of Oral & Dental Science, University of Bristol Dental
School, Lower Maudlin Street, Bristol, BS1 2LY, UK.
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 microM) and lysophosphatidic acid (LPA, 20 microM) 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 microM) and LPA (20 microM) as demonstrated by stark,
synergistic increases in ALP activity. Evidence of activator protein-1
(AP-1) stimulation by LCA acetate (30 microM) 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 microM) and either epidermal growth
factor (10 ng/ml) or transforming growth factor-beta (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.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19646460