二甲双胍治疗骨质疏松症的机制及研究进展
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摘要
糖尿病和骨质疏松症是影响老年人健康和寿命的两大常见疾病,糖尿病患者往往伴有骨密度降低、骨量下降、容易骨折等症状.二甲双胍作为一种治疗Ⅱ型糖尿病的传统口服降糖药,在治疗骨质疏松症方面能够发挥一定的作用.近年来,二甲双胍在骨代谢中发挥的作用备受研究人员的关注.基于此,从动物模型、细胞水平和分子水平3个方面综述了二甲双胍治疗骨质疏松症的机制及研究进展.
Diabetes mellitus and osteoporosis are two common diseases affecting the health and longevity of the elderly. Diabetes patients often have bone density reduction,bone mass loss,fracture and other symptoms. Metformin,as a traditional oral medicine for the treatment of type Ⅱ diabetes,also plays a role in the treatment of osteoporosis. In recent years,more and more studies have focused on the role of metformin in bone metabolism. Because of this,the mechanism and research progress of metformin in the treatment of osteoporosis has been summarized from the three aspects: animal model,cell level and molecular level.
Diabetes mellitus and osteoporosis are two common diseases affecting the health and longevity of the elderly. Diabetes patients often have bone density reduction,bone mass loss,fracture and other symptoms. Metformin,as a traditional oral medicine for the treatment of type Ⅱ diabetes,also plays a role in the treatment of osteoporosis. In recent years,more and more studies have focused on the role of metformin in bone metabolism. Because of this,the mechanism and research progress of metformin in the treatment of osteoporosis has been summarized from the three aspects: animal model,cell level and molecular level.
引文
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[18] ROSEN E D,HSU C H,WANG X Z,et al. C/EBPαinduces adipogenesis through PPARγ:a unified pathway[J]. Gene Dev,2002,16(1):22-26.
[19] YASUDA H,SHIMA N,NAKAGAWA N,et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL[J]. Proc Natl Acad Sci USA,1998,95(7):3597-3602.
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[21] KANAZAWA I,YAMAGUCHI T,YANO S,et al.Adiponectin and AMP kinase activator stimulate proliferation,differentiation, and mineralization of osteoblastic MC3T3-E1 cells[J]. BMC Cell Biol,2007,51(8):1-12.
[22] KANAZAWA I,YAMAGUCHI T,YANO S,et al.Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as e NOS and BMP-2 expression[J]. Biochem Bioph Res Co,2008,375(3):414-419.
[2] RKEL A,SHEEHY O,RAHME E,et al. Osteoporosis among patients with type 1 and type 2 diabetes[J].Diabetes Metab,2008,34(3):193-205.
[3] KIRPICHNIKOV D,MCFRLANE S I,SOWERS J R.Metformin:an update[J]. Ann Intern Med, 2002,137(1):25-33.
[4] GAO Y,LI Y F,XUE J,et al. Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats[J]. Eur J Pharmacol,2010,635(3):231-236.
[5] MAI Q G,ZHANG Z M,XU S,et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats[J]. J Cell Biochem,2011,112(10):2902-2909.
[6]周根祥,高莺,闫文婷,等.二甲双胍对去势大鼠胫骨生物力学影响的研究[J].临床口腔医学杂志,2017,33(6):342-344.
[7] BENAYAHU D,SHUR I,BEN-ELIYAHU S. Hormonal changes affect the bone and bone marrow cells in a rat model[J]. J Cell Biochem,2000,79(3):407-415.
[8] PINO A M,ROSEN C J,RODRIGUEZ J P. In osteoporosis,differentiation of mesenchymal stem cells(MSCs)improves bone marrow adipogenesis[J]. Biol Res,2012,45(3):279-287.
[9] GAO Y,XUE J,LI XY,et al. Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells[J]. J Pharm Pharmacol,2008,60(12):1695-1700.
[10]张海波,梁伟之,高莺,等.二甲双胍对骨向分化骨髓基质细胞增殖和分化的影响[J].医学研究杂志,2011,40(10):131-133.
[11]张海波,张绍军,高莺,等.二甲双胍对脂向分化间充质干细胞的影响[J].医学研究杂志,2009,38(12):55-57.
[12] WANG P,MA T,GUO D,et al. Metformin induces osteoblastic differentiation of human induced pluripotent stem cell-derivedmesenchymal stem cells[J]. J Tissue Eng Regen Med,2018,12(2):437-446.
[13] GU Q L,GU Y Z,YANG H L,et al. Metformin enhances osteogenesis and suppresses adipogenesis of human chorionic villous mesenchymal stem cells[J].Tohoku J Exp Med,2017,241(1):13-19.
[14] CORTIZO A M,SEDLINSKY C,MCCARTHY A D,et al.Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture[J]. Eur J Pharmacol,2006,536(2):38-46.
[15]吕娇,刘洪臣,鄂玲玲,等.盐酸二甲双胍对大鼠下颌骨成骨细胞增殖、分化及矿化功能的影响[J].中华老年口腔医学杂志,2008,6(1):47-50.
[16] DUCY P,STARBUCK M,PRIEMEL M,et al. A cbfa1-dependent genetic pathway controls bone formation beyond embryonic development[J]. Genes Dev,1999,13(8):1025-1036.
[17]王石颖,闫素梅.碱性磷酸酶在动物骨骼代谢中的研究进展[J].饲料博览,2009(4):14-16.
[18] ROSEN E D,HSU C H,WANG X Z,et al. C/EBPαinduces adipogenesis through PPARγ:a unified pathway[J]. Gene Dev,2002,16(1):22-26.
[19] YASUDA H,SHIMA N,NAKAGAWA N,et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL[J]. Proc Natl Acad Sci USA,1998,95(7):3597-3602.
[20] TEITELBAUM S L. Bone resorption by osteoclasts[J].Science,2000,289:1504-1508.
[21] KANAZAWA I,YAMAGUCHI T,YANO S,et al.Adiponectin and AMP kinase activator stimulate proliferation,differentiation, and mineralization of osteoblastic MC3T3-E1 cells[J]. BMC Cell Biol,2007,51(8):1-12.
[22] KANAZAWA I,YAMAGUCHI T,YANO S,et al.Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as e NOS and BMP-2 expression[J]. Biochem Bioph Res Co,2008,375(3):414-419.