title: In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice.
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.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Christina C W
authors.initials: CC
authors.lastname: Poon
authors.affiliation: 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.
authors.forename: Rachel W S
authors.initials: RW
authors.lastname: Li
authors.affiliation: National Institute of Complementary Medicine, School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia.
authors.forename: Sai Wang
authors.initials: SW
authors.lastname: Seto
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Siu Kai
authors.initials: SK
authors.lastname: Kong
authors.affiliation: Department of Electronic Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ho Pui
authors.initials: HP
authors.lastname: Ho
authors.affiliation: Institute of Chinese Medical Sciences, The University of Macau, Macau, China.
authors.forename: Maggie P M
authors.initials: MP
authors.lastname: Hoi
authors.affiliation: Institute of Chinese Medical Sciences, The University of Macau, Macau, China.
authors.forename: Simon M Y
authors.initials: SM
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Sai Ming
authors.initials: SM
authors.lastname: Ngai
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Shun Wan
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Department of Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong. Electronic address: gphleung@hku.hk.
authors.forename: George P H
authors.initials: GP
authors.lastname: Leung
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address: yiuwakwan@cuhk.edu.hk.
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Kwan
mesh_terms: D051701:Activating Transcription Factor 4; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004357:Drug Synergism; D018398:Homeodomain Proteins; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000494:pharmacology*
chemical_list: C081452:Atf4 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C118756:dihydroxy-vitamin D3; D015675:Osteocalcin; D024482:Vitamin K 2; D014807:Vitamin D; D051701:Activating Transcription Factor 4; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium
keywords: 1,25(OH)(2)D(3); Osteoblasts; Osteoporosis; Type 2 diabetes mellitus; Vitamin K(2)