Gizem Celebi1,2,3, Merve Anapali4,5, Fatma Kaya Dagistanli4, Ayse Seda Akdemir4, Duygu Aydemir6,7, Nuriye Nuray Ulusu6,7, Turgut Ulutin4, Evrim Komurcu-Bayrak8,9. 1. Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. gizemcelebi@sabanciuniv.edu. 2. Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey. gizemcelebi@sabanciuniv.edu. 3. Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, 34956, Istanbul, Turkey. gizemcelebi@sabanciuniv.edu. 4. Cerrahpasa Medical Faculty, Medical Biology Department, Istanbul University-Cerrahpasa, Istanbul, Turkey. 5. Medical Biology Department, Ataturk University Medical Faculty, Erzurum, Turkey. 6. School of Medicine, Department of Medical Biochemistry, Koç University, 34450, Sariyer, Istanbul, Turkey. 7. Koç University Research Center for Translational Medicine (KUTTAM), 34450, Sariyer, Istanbul, Turkey. 8. Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. 9. Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul University, Istanbul, Turkey.
Abstract
BACKGROUND: Type 2 Diabetes Mellitus is a chronic metabolic disease that causes endothelial damage and is an important risk factor for atherosclerosis. In the present study vitamin D3 supplementation in rats was used to determine the role of Osteoprotegerin (OPG)/Receptor activator kB ligand (RANKL) signalling in endothelial damage and changes in the expression levels of genes involved in this pathway. We hypothesized that vitamin D3 supplementation affects OPG and RANKL activity in the aorta. METHODS: Diabetes was induced in rats via injections of 40 mg/kg of streptozotocin followed by a high fructose (10%) diet. Group 2 (healthy) and 4 (diabetic) received 170 IU/kg of vitamin D3 weekly for 5 weeks, while Group 1 (healthy) and 2 (diabetic) received sterile saline. The aortas of each group were collected to analyse mRNA expression using the real-time PCR method and also to evaluate magnesium and calcium levels using inductively coupled plasma mass spectrometry. RESULTS: Opg and Il-1b expression levels were significantly associated with both diabetes and vitamin D3 supplementation in the aortas of the study groups (p ≤ 0.05). Opg mRNA expression was also found to correlate with both Icam-1 and Nos3 mRNA expression levels (r = 0.699, p = 0.001 and r = 0.622, p = 0.003, respectively). In addition, when mineral levels in the aortic tissues were compared among all groups, it was found that the interaction of diabetes and vitamin D3 supplementation significantly affected Mg levels and Mg/Ca ratios. CONCLUSIONS: It is concluded that vitamin D3 supplementation has a modulatory effect on OPG/RANKL activity in the vessel wall by ameliorating endothelial damage in diabetes. This effect may contribute to the regulation of cytokine-mediated vascular homeostasis and mineral deposition in the aorta; therefore, further comprehensive studies are proposed to demonstrate this relationship.
BACKGROUND: Type 2 Diabetes Mellitus is a chronic metabolic disease that causes endothelial damage and is an important risk factor for atherosclerosis. In the present study vitamin D3 supplementation in rats was used to determine the role of Osteoprotegerin (OPG)/Receptor activator kB ligand (RANKL) signalling in endothelial damage and changes in the expression levels of genes involved in this pathway. We hypothesized that vitamin D3 supplementation affects OPG and RANKL activity in the aorta. METHODS: Diabetes was induced in rats via injections of 40 mg/kg of streptozotocin followed by a high fructose (10%) diet. Group 2 (healthy) and 4 (diabetic) received 170 IU/kg of vitamin D3 weekly for 5 weeks, while Group 1 (healthy) and 2 (diabetic) received sterile saline. The aortas of each group were collected to analyse mRNA expression using the real-time PCR method and also to evaluate magnesium and calcium levels using inductively coupled plasma mass spectrometry. RESULTS: Opg and Il-1b expression levels were significantly associated with both diabetes and vitamin D3 supplementation in the aortas of the study groups (p ≤ 0.05). Opg mRNA expression was also found to correlate with both Icam-1 and Nos3 mRNA expression levels (r = 0.699, p = 0.001 and r = 0.622, p = 0.003, respectively). In addition, when mineral levels in the aortic tissues were compared among all groups, it was found that the interaction of diabetes and vitamin D3 supplementation significantly affected Mg levels and Mg/Ca ratios. CONCLUSIONS: It is concluded that vitamin D3 supplementation has a modulatory effect on OPG/RANKL activity in the vessel wall by ameliorating endothelial damage in diabetes. This effect may contribute to the regulation of cytokine-mediated vascular homeostasis and mineral deposition in the aorta; therefore, further comprehensive studies are proposed to demonstrate this relationship.
Authors: I Barchetta; V Ceccarelli; F A Cimini; L Bertoccini; A Fraioli; C Alessandri; A Lenzi; M G Baroni; M G Cavallo Journal: J Endocrinol Invest Date: 2018-08-21 Impact factor: 4.256
Authors: Luis F de Castro; Andrea B Burke; Howard D Wang; Jeffrey Tsai; Pablo Florenzano; Kristen S Pan; Nisan Bhattacharyya; Alison M Boyce; Rachel I Gafni; Alfredo A Molinolo; Pamela G Robey; Michael T Collins Journal: J Bone Miner Res Date: 2018-11-29 Impact factor: 6.741
Authors: Brian J Bennett; Marta Scatena; Elizabeth A Kirk; Marcello Rattazzi; Rebecca M Varon; Michelle Averill; Stephen M Schwartz; Cecilia M Giachelli; Michael E Rosenfeld Journal: Arterioscler Thromb Vasc Biol Date: 2006-07-13 Impact factor: 8.311