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Eur J Pharmacol. 2015 Nov 15;767:30-40. doi: 10.1016/j.ejphar.2015.09.048. Epub 2015 Oct 8.

In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice.

Author information

1
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
2
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; Department of Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong.
3
National Institute of Complementary Medicine, School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia.
4
School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong.
5
Department of Electronic Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Hong Kong.
6
Institute of Chinese Medical Sciences, The University of Macau, Macau, China.
7
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
8
Department of Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong. Electronic address: gphleung@hku.hk.
9
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address: yiuwakwan@cuhk.edu.hk.

Abstract

In this study, we evaluated the anabolic effect and the underlying cellular mechanisms involved of vitamin K2 (10 nM) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) (10 nM), alone and in combination, on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (+/+) and obese/diabetic (db/db) mice. A lower alkaline phosphatase (ALP) activity plus a reduced expression of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4 and OSX) were consistently detected in osteoblasts of db/db mice compared to lean mice. A significantly higher calcium deposits formation in osteoblasts was observed in lean mice when compared to db/db mice. Co-administration of vitamin K2 (10 nM) and 1,25(OH)2D3 (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K2 and 1,25(OH)2D3 co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and bone formation transcription factors, with a greater magnitude of increase observed in osteoblasts of db/db mice. Combined vitamins K2 plus 1,25(OH)2D3 treatment significantly enhanced migration and the re-appearance of surface microvilli and ruffles of osteoblasts of db/db mice. Thus, our results illustrate that vitamins K2 plus D3 combination could be a novel therapeutic strategy in treating diabetes-associated osteoporosis.

KEYWORDS:

1,25(OH)(2)D(3); Osteoblasts; Osteoporosis; Type 2 diabetes mellitus; Vitamin K(2)

PMID:
26452518
DOI:
10.1016/j.ejphar.2015.09.048
[Indexed for MEDLINE]

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