2型糖尿病合并不同骨量患者外周血Runx2 mRNA表达与25(OH)D的关系
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摘要
目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并不同骨量患者血浆中转录受体相关转录因子-2 (Runt-related transcription factor-2,Runx2) mRNA表达与25-羟基维生素D[25 hydroxyvitamin D,25(OH)D]的关系。方法选取2016年7月至2017年6月就诊于遵义医学院附属医院骨科和内分泌科住院的初诊2型糖尿病患者150例,根据骨密度结果分为T2DM+骨量正常组(A组)50例、T2DM合并骨量减少组(B组)50例、T2DM合并骨质疏松组(C组)50例。收集同期我院体检中心年龄、性别相匹配的健康体检者为正常对照组(NC组)50名。采用电化学发光法检测血清25(OH)D水平,实时荧光定量聚合酶链反应(Real Time-PCR)检测外周血中Runx2 mRNA的表达水平。结果①A组空腹血浆葡萄糖(fasting plasma ghlcose,FPG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、低密度脂蛋白胆固醇(lipoprotein-cholesterol,LDL-C)较NC组明显升高,而HDL-C明显降低(P<0.05);②C组25(OH)D、Runx2 mRNA水平显著低于NC组、A组及B组;B组低于NC组及A组;A组低于NC组,即C组 Objective This study aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and runt-related transcription factor-2(Runx2) gene expression in type 2 diabetic patients with various levels of bone mineral density(BMD). Methods A total of 150 patients with type 2 diabetes mellitus(T2 DM) admitted to the department of endocrinology, Affiliated Hospital of Zunyi Medical College between July 2016 and June 2017 were recruited. All patients were divided into three groups according to measurements of BMD: 50 cases in T2 DM with normal BMD group(Group A), 50 cases in T2 DM with osteopenia group(Group B), and 50 cases in T2 DM with osteoporosis group(Group C). Fifty healthy individuals matched for age and gender were recruited from the physical examination center and defined as controls(Group NC). Serum 25(OH)D concentrations in patients were evaluated using electrochemiluminescence immunoassay(ECLIA) and Runx2 gene expression was measured by quantitative real-time PCR(qPCR). Results ECLIA revealed that FPG, HbA1 c, HOMA-IR and LDL-C levels were significantly increased in Group A relative to Group NC, but HDL-C levels were significantly lower(P<0.05). qPCR showed that mRNA expressions of Runx2 were directly proportional to bone mass: Group C < Group B < Group A < Group NC(P<0.05). There was a positive correlation between serum 25(OH)D concentrations and Runx2 mRNA expression using the Pearson correlation coefficient(r=0.548, P<0.05), whereas serum 25(OH)D had a negative correlation with HbA1 c, HOMA-IR, and TG(the r values were-0.315,-0.323, and-0.348, respectively)(P<0.05). Conclusion Our result suggest that both serum 25(OH)D concentrations and Runx2 mRNA expression were reduced in peripheral blood, which may be involved in the development of T2 DM with osteoporosis.
引文
[1] He R, Shen J, Liu F, et al.Vitamin D deficiency increases the risk of retinopathy in Chinese patients with type 2 diabetes[J]. Diabet Med, 2014, 31(12):1657-1664.
[2] Menezes AR, Lamb MC, Lavie CJ, et al.Vitamin D and atherosclerosis[J]. Curr Opin Cardiol, 2014, 29(6): 571-577.
[3] Junq CH,Kim KJ,Kim BY,et al.Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus[J].Nutr Res,2016,36(2):117-124.
[4] Berridge MJ.Vitamin D deficiency and diabetes[J].Biochem J,2017,474(8):1321-1332.
[5] Mitri J, Dawson-Hughes B, Hu FB, et al. Effects of vitamin D and calcium supplementation on pancreatic β-cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial[J]. Am J Clin Nutr,2011, 94(2):486-494.
[6] Gohzman D,Li Y,Xi B,et al.Inferences from genetically modified nlouse models on the skeletal actions of vitamin D[J].J Steroid Biochem Mol Biol,2015,148(6):219-224.
[7] Ma HP,Ming LG,Ge BF,et al.Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro[J].J Cell Biochem,2011,112(3):916-923.
[8] Albers J,Keller J,Baranowsky A,et al.Canonical Wnt signaling inhibits osteocla-stogenesis independent of osteoprotegerin[J].J Cell Biol,2013,200(4):537-549.
[9] Okamura H,Yang D,Yoshida K,et al.Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression[J].Biochimica Et Biophysica Acta,2014,1843(11):2376-2384.
[10] Florencia A.IDF Diabetes Atlas[M].Sixth edition.International Diabetes Fede-Ration,2013.
[11] 许兵,方剑利,刘慧,等.补肾活血方对去势大鼠骨质疏松的影响[J].中华骨质疏松和骨矿盐疾病杂志,2011,4(3):177-182.
[12] Oei L,Zillikens MC,Dehghan A, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: The rotterdam study[J]. Diabetes Care, 2013, 36(6):1619-1628.
[13] Napoli N,Chandran M,Pierroz DD,et al. Mechanisms of diabetes mellitus-induced bone fragility[J].Nat Rev Endocrinol,2017,13(4):208-219.
[14] Goldshtein I,Nguyen AM,Depapp AE,et al.Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients[J]. Archives of Osteoporosis, 2018,13(1):15.
[15] Wimalawansa SJ.Associations of vitamin D with insulin resistance,obesity,type 2 diabetes,and metabolic syndrome[J]. J Steroid Biochem Mol Biol,2018,175:177-189.
[16] Kostoglou-Athanassiou I,Athanassiou P,Gkountouvas A,et al.Vitamin D and glycemic control in diabetes mellitus type 2[J]. Ther Adv Endocrinol Metab,2013, 4(4): 122-128.
[17] Wang X, Schr?der HC, Feng Q, et al. Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast-like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 and Ets1[J]. Biochemical Pharmacology,2014,89(3):413-421.
[18] Zhang M, Bian YQ, Tao HM, et al. Simvastatin induces osteogenic differentiation of MSCs via Wnt/β-catenin pathway to promote fracture healing[J]. European review for medical and pharmacological sciences,2018, 22(9):2896.
[19] Boyan BD,Chen J,Schwartz Z.Mechanism of Pdia3-dependent 1α,25-dihydroxy vitamin D3 signaling in musculoskeletal cells[J].Steroids,2012,77(10):892-896.
[20] Mehmood ZTNH,Papandreou D. An updated mini review of Vitamin D and obesity: Adipogenesis and inflammation state[J].Open Access Macedonian Journal of Medical Sciences,2016,4(3):526-532.
[21] Saneei P, Sal ehi-AbargoueiA, Esmaill zadeh A. Serum 25-hydroxy vitamin D levels in relation to body mass index: a system atic review and meta-analysis[J]. Obes Rev, 2013,14(5):393-404.
[22] Han B, Li Q, Wang N, et al. Sexual dimorphism for the association between Vitamin D and insulin resistance in Chinese people[J].Int J Endocrinol, 2018,2018:1216370.
[23] Wen J, Hong Q, Wang X, et al. The effect of maternal vitamin D deficiency during pregnancy on body fat and adipogenesis in rat offspring[J]. Sci Rep, 2018,8(1):365.
[2] Menezes AR, Lamb MC, Lavie CJ, et al.Vitamin D and atherosclerosis[J]. Curr Opin Cardiol, 2014, 29(6): 571-577.
[3] Junq CH,Kim KJ,Kim BY,et al.Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus[J].Nutr Res,2016,36(2):117-124.
[4] Berridge MJ.Vitamin D deficiency and diabetes[J].Biochem J,2017,474(8):1321-1332.
[5] Mitri J, Dawson-Hughes B, Hu FB, et al. Effects of vitamin D and calcium supplementation on pancreatic β-cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial[J]. Am J Clin Nutr,2011, 94(2):486-494.
[6] Gohzman D,Li Y,Xi B,et al.Inferences from genetically modified nlouse models on the skeletal actions of vitamin D[J].J Steroid Biochem Mol Biol,2015,148(6):219-224.
[7] Ma HP,Ming LG,Ge BF,et al.Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro[J].J Cell Biochem,2011,112(3):916-923.
[8] Albers J,Keller J,Baranowsky A,et al.Canonical Wnt signaling inhibits osteocla-stogenesis independent of osteoprotegerin[J].J Cell Biol,2013,200(4):537-549.
[9] Okamura H,Yang D,Yoshida K,et al.Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression[J].Biochimica Et Biophysica Acta,2014,1843(11):2376-2384.
[10] Florencia A.IDF Diabetes Atlas[M].Sixth edition.International Diabetes Fede-Ration,2013.
[11] 许兵,方剑利,刘慧,等.补肾活血方对去势大鼠骨质疏松的影响[J].中华骨质疏松和骨矿盐疾病杂志,2011,4(3):177-182.
[12] Oei L,Zillikens MC,Dehghan A, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: The rotterdam study[J]. Diabetes Care, 2013, 36(6):1619-1628.
[13] Napoli N,Chandran M,Pierroz DD,et al. Mechanisms of diabetes mellitus-induced bone fragility[J].Nat Rev Endocrinol,2017,13(4):208-219.
[14] Goldshtein I,Nguyen AM,Depapp AE,et al.Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients[J]. Archives of Osteoporosis, 2018,13(1):15.
[15] Wimalawansa SJ.Associations of vitamin D with insulin resistance,obesity,type 2 diabetes,and metabolic syndrome[J]. J Steroid Biochem Mol Biol,2018,175:177-189.
[16] Kostoglou-Athanassiou I,Athanassiou P,Gkountouvas A,et al.Vitamin D and glycemic control in diabetes mellitus type 2[J]. Ther Adv Endocrinol Metab,2013, 4(4): 122-128.
[17] Wang X, Schr?der HC, Feng Q, et al. Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast-like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 and Ets1[J]. Biochemical Pharmacology,2014,89(3):413-421.
[18] Zhang M, Bian YQ, Tao HM, et al. Simvastatin induces osteogenic differentiation of MSCs via Wnt/β-catenin pathway to promote fracture healing[J]. European review for medical and pharmacological sciences,2018, 22(9):2896.
[19] Boyan BD,Chen J,Schwartz Z.Mechanism of Pdia3-dependent 1α,25-dihydroxy vitamin D3 signaling in musculoskeletal cells[J].Steroids,2012,77(10):892-896.
[20] Mehmood ZTNH,Papandreou D. An updated mini review of Vitamin D and obesity: Adipogenesis and inflammation state[J].Open Access Macedonian Journal of Medical Sciences,2016,4(3):526-532.
[21] Saneei P, Sal ehi-AbargoueiA, Esmaill zadeh A. Serum 25-hydroxy vitamin D levels in relation to body mass index: a system atic review and meta-analysis[J]. Obes Rev, 2013,14(5):393-404.
[22] Han B, Li Q, Wang N, et al. Sexual dimorphism for the association between Vitamin D and insulin resistance in Chinese people[J].Int J Endocrinol, 2018,2018:1216370.
[23] Wen J, Hong Q, Wang X, et al. The effect of maternal vitamin D deficiency during pregnancy on body fat and adipogenesis in rat offspring[J]. Sci Rep, 2018,8(1):365.