A NOVEL VITAMIN-D ANALOG WITH 2 DOUBLE-BONDS IN ITS SIDE-CHAIN - A POTENT INDUCER OF OSTEOBLASTIC CELL-DIFFERENTIATION

Citation
A. Mahonen et al., A NOVEL VITAMIN-D ANALOG WITH 2 DOUBLE-BONDS IN ITS SIDE-CHAIN - A POTENT INDUCER OF OSTEOBLASTIC CELL-DIFFERENTIATION, Biochemical pharmacology, 51(7), 1996, pp. 887-892
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
0006-2952
Volume
51
Issue
7
Year of publication
1996
Pages
887 - 892
Database
ISI
SICI code
0006-2952(1996)51:7<887:ANVAW2>2.0.ZU;2-G
Abstract
EB 1089 (1 a,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D-3) is a novel, synthetic analog of calcitriol, characterized by two extra do uble bonds in its side chain. It is less potent than calcitriol in its calcemic action, but is an order of magnitude more potent in its anti proliferative action. The aim of this study was to determine the abili ty of EB 1089 to induce the well-known biological effects of calcitrio l in MG-63 human osteosarcoma cells (i.e. by inhibiting cell prolifera tion and by induction of differentiation). Both calcitriol and EB 1089 significantly decreased cell growth after 2 days in culture. At 5 day s, however, EB 1089 was more potent than the natural hormone in inhibi ting the proliferation of MG-63 cells. Potent effects of EB 1089 on ce ll differentiation were also seen in the stimulation of alkaline phosp hatase activity, cellular vitamin D receptor mRNA levels, and medium o steocalcin synthesis. EB 1089 was clearly more effective than calcitri ol in stimulating alkaline phosphatase activity and osteocalcin synthe sis. In gel shift assays, the binding of vitamin D receptor to the com posite AP-1 plus vitamin-D-responsive promoter region of the human ost eocalcin gene after EB 1089 treatment was stronger and longer-lasting than after calcitriol treatment.