In vitro vitamin K2 and 1α,25-dihydroxyvitamin D3 combination enhances osteoblasts anabolism of diabetic mice

Authors

Christina C.W. Poon, The Chinese University of Hong Kong
Rachel W.S. Li, The Chinese University of Hong Kong
Sai Wang Seto, University of Western Sydney
Siu Kai Kong, The Chinese University of Hong Kong
Ho Pui Ho, The Chinese University of Hong Kong
Maggie P.M. Hoi, The University of Macau
Simon M.Y. Lee, University of Macau
Sai Ming Ngai, The Chinese University of Hong Kong
Shun Wan Chan, Technological and Higher Education Institute of Hong Kong, Vocational Training CouncilFollow
George P.H. Leung, The University of Hong Kong
Yiu Wa Kwan, The Chinese University of Hong Kong

Staff Page Link

Dr CHAN Shun Wan

Document Type

Journal Article

Publication Date

2015

Keywords

Type 2 diabetes mellitus, Osteoporosis, Osteoblasts, Vitamin K2, 1, 25(OH)2D3

DOI

10.1016/j.ejphar.2015.09.048

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.

Source Publication

European Journal of Pharmacology

Volume Number

767

First Page

30

Last Page

40

Recommended Citation

Poon, C.,Li, R.,Seto, S.,Kong, S.,Ho, H.,Hoi, M.,Lee, S.,Ngai, S.,Chan, S.,Leung, G.,& Kwan, Y. (2015). In vitro vitamin K2 and 1α,25-dihydroxyvitamin D3 combination enhances osteoblasts anabolism of diabetic mice. European Journal of Pharmacology, 767, 30-40. http://dx.doi.org/10.1016/j.ejphar.2015.09.048