Morichika Takita
   Department   School of Medicine, School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Novel vitamin D3 analogs, 1α,25(OH)2D3-26,23-lactam (DLAMs), antagonize bone resorption via suppressing RANKL expression in osteoblasts.
Journal Formal name:Biochemical and Biophysical Research Commmunications
Abbreviation:Biochem. Biophys. Res. Commn.
ISSN code:0006291X
Domestic / ForeginForegin
Publisher Elsevier
Volume, Issue, Page 372,pp.434-439
Author and coauthor Inada Masaki†, Tsukamoto Kazuki, Hirata Michiko, Takita Morichika, Nagasawa Kazuo, Miyaura Chisato*
Publication date 2008/05
Summary Novel vitamin D analogs, 1alpha, 25-dihydroxyvitamin D(3)-26, 23-lactam (DLAMs) with a lactam moiety in the side chain, were synthesized and examined for their function in bone. In computer docking simulation, DLAM-1P binds to vitamin D receptor (VDR), and its lactam moiety may interfere with VDR helix-12 folding. In co-cultures of mouse bone marrow cells and osteoblasts, (23S,25S)-DLAM-1P dose-dependently suppressed osteoclast differentiation induced by 1alpha, 25-dihydroxyvitamin D(3) [1alpha, 25(OH)(2)D(3)]. Its stereoisomer (23R,25R)-DLAM-1P did not affect the osteoclast differentiation. In osteoblasts, (23S,25S)-DLAM-1P suppressed 1alpha, 25(OH)(2)D(3)-induced mRNA expression of the receptor activator of NF-kappaB ligand (RANKL). In an organ culture using mouse calvaria, bone-resorbing activity induced by 1alpha, 25(OH)(2)D(3) was clearly suppressed by (23S,25S)-DLAM-1P. The other analog, (23S,25S)-DLAM-2P, showed a similar activity to (23S,25S)-DLAM-1P. Therefore, DLAMs act on osteoblasts as an antagonist of 1alpha, 25(OH)(2)D(3) to suppress RANKL-dependent osteoclast formation, suggesting them as a novel candidate for the treatment of pathological bone loss.
DOI 10.1016/j.bbrc.2008.05.041
PMID 18489902