In vitro vitamin K2 and 1α,25-dihydroxyvitamin D3 combination enhances osteoblasts anabolism of diabetic mice
Type 2 diabetes mellitus, Osteoporosis, Osteoblasts, Vitamin K2, 1, 25(OH)2D3
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.
European Journal of Pharmacology
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