您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (3): 56-61.doi: 10.6040/j.issn.1671-7554.0.2014.744

• 基础医学 • 上一篇    下一篇

1型糖尿病大鼠Runx2、Osterix表达变化及唑来膦酸的干预作用

赵旭, 崔敏, 于灵芝, 张娜, 曹鲁宁   

  1. 山东大学附属济南市中心医院疼痛科, 山东 济南 250013
  • 收稿日期:2014-10-27 修回日期:2015-02-28 出版日期:2015-03-10 发布日期:2015-03-10
  • 通讯作者: 于灵芝, E-mail:pain-relif@163.com E-mail:pain-relif@163.com
  • 基金资助:
    山东省科技攻关计划(2011GSF11817)

Changes of Runx2 and Osterix expression in type 1 diabetic rats and the intervention effect of zoledronic acid

ZHAO Xu, CUI Min, YU Lingzhi, ZHANG Na, CAO Luning   

  1. Department of Pain Management, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
  • Received:2014-10-27 Revised:2015-02-28 Online:2015-03-10 Published:2015-03-10

摘要: 目的 观察1型糖尿病大鼠血清胰岛素和骨钙素水平, 骨组织Runx2和Osterix(OSX)基因转录水平及唑来膦酸的干预作用。方法 Wistar雌性大鼠170只, 随机分为正常对照组(n=40)和糖尿病模型组(n=130)。糖尿病模型组一次性腹腔注射链脲佐菌素(60 mg/kg)制作1型糖尿病模型, 随机选取120只分为模型组、预防组和治疗组, 每组40只。预防组和治疗组分别在造模成功和造模成功2周后静脉给予唑来膦酸(0.1 mg/kg)。ELISA法检测血清胰岛素和骨钙素水平;RT-PCR法检测右侧股骨Runx2和OSX mRNA表达水平。结果 模型组、预防组和治疗组与正常对照组相比, 血清胰岛素水平显著下降(P<0.05)。骨钙素水平模型组显著低于正常对照组(P<0.05),预防组高于正常对照组和模型组(P<0.05),治疗组在12周高于预防组(P<0.05)。模型组骨组织Runx2和OSX mRNA表达水平与正常对照组相比显著降低(P<0.05), 预防组和治疗组表达均明显高于正常对照组和模型组(P<0.05), 预防组表达上调程度高于治疗组。结论 在1型糖尿病大鼠模型中, 骨组织Runx2和OSX mRNA表达水平显著下降;预防性应用唑来膦酸可逆转Runx2和OSX mRNA表达的下降, 促进骨形成。

关键词: Osterix, 1型糖尿病, Runx2, 唑来膦酸, 胰岛素, 骨钙素

Abstract: Objective To observe the levels of serum insulin and osteocalcin, osteoblast specific transcription factor Runx2 and Osterix (OSX) gene in type 1 diabetic rats, and the intervention effect of zoledronic acid. Methods A total of 170 Wistar rats were randomly divided into two groups:40 rats were enrolled into the control group the other animals were injected with streptozotocin (60 mg/kg) to establish type 1 diabetic models. After that, 120 rats in this group were randomly divided into the model group (n=40), prevention group (n=40) and treatment group (n=40). Rats in the prevention group and treatment group received a bolus injection of zoledronic acid (0.1 mg/kg) at the onset of diabetes and 2 weeks later, respectively. The serum INS and OC were detected with ELISA. Expressions of Runx2 and OSX mRNA in the right femur were detected with RT-PCR. Results ELISA results showed that the serum INS in the model group, prevention group and treatment group was significantly reduced compared with that in the control group (P<0.05). The serum OC was lower in the model group that in the control group (P<0.05), while higher in the prevention group than in the control group and model group (P<0.05). At week 12, serum OC was higher in the treatment group than in the prevention group (P<0.05). RT-PCR tests showed that the expressions of Runx2 andOSX mRNA were significantly lower in the model group than in the control group (P<0.05), while remarkably higher in the prevention group and treatment group than in the control group and model group (P<0.05). The upregulation was higher in the prevention group than in the model group. Conclusion Expressions of Runx2 and OSX mRNA were significantly decreased in the bone of type 1 diabetic rat models. Prophylactic use of zoledronic acid can improve the levels of serum OC, and reverse the decreasing expression of Runx2 and OSX mRNA, thus promoting bone formation.

Key words: Insulin, Osteocalcin, Runx2, Type 1 diabetes, Osterix, Zoledronic acid

中图分类号: 

  • R589
[1] Okazaki K, Sandell LJ. Extracellular matrix gene regulation[J]. Clin Orthop Relat Res, 2004, 427(Supp1):123-128.
[2] Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation[J]. Cell, 2002, 108(1):17-29.
[3] Choi C, Lee H, Lim H, et al. Effect of rubus coreanus extracts on diabetic osteoporosis by simultaneous regulation of osteoblasts and osteoblasts[J]. Menopause, 2012, 19(9):1043-1051.
[4] Mccabe LR. Understanding the pathology and mechanisms of type I diabetic bone loss[J]. J Cell Biochem, 2007, 102(6):1343-1357.
[5] 吴璇, 刘洪臣, 鄂玲玲, 等. 胰岛素对糖尿病大鼠下颌骨成骨细胞分化的影响[J]. 口腔医学研究, 2014, 30(5):407-410. WU Xuan, LIU Hongchen, E Lingling, et al. Effect of Insulin on differentiation of osteoblasts obtained from diabetic rats' mandible[J]. Journal of Oral Science Research, 2014, 30(5):407-410.
[6] Hou JM, Wu M, Lin QM, et al. Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression[J]. Mol Biol Rep, 2014, 41(8):5019-5030.
[7] Enomoto H, Enomoto-Iwamoto M, Iwamoto M, et al. Cbfa1 is a positive regulatory factor in chondrocyte maturation[J]. J Biol Chem, 2000, 275(12):8695-8702.
[8] Wang WJ, Sun C, Liu Z, et al. Transcription factor Runx2 in the low bone mineral density of girls with adolescent idiopathic scoliosis[J]. Orthop Surg, 2014, 6(1):8-14.
[9] 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.
[10] Lu H, Kraut D, Gerstenfeld LC, et al. Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation[J]. Endoc rinology, 2003, 144(1):346-352.
[11] 于灵芝, 张娜, 崔敏, 等. 脉冲电磁场对大鼠成骨细胞增殖、分化及osterix基因表达的影响[J]. 中华物理医学与康复杂志, 2012, 34(7):485-487. YU Lingzhi, ZHANG Na , CUI Min, et al. Effects of a pulsed electromagnetic field on cell proliferation, differentiation and osterix mRNA expression in rat osteoblasts[J]. Chinese Journal of Physical Medicine and Rehabilitation, 2012, 34(7):485-487.
[12] Matsubara T, Kida K, Yamaguchi A, et al. BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation[J]. J Biol Chem, 2008, 283(43):29119-29125.
[13] Huang S, Lin H, Zhu X, et al. Zoledronic acid increases bone mineral density and improves health-related quality of life over two years of treatment in Chinese women with postmenopausal osteoporosis[J]. Endokrynol Pol, 2014, 65(2):96-104.
[14] 彭晨, 王志强, 李琪佳, 等. 唑来膦酸对大鼠成骨细胞增殖、分化和护骨素/核因子κB受体激动剂配体mRNA表达的影响[J]. 中国组织工程研究与临床康复, 2009, 13(22):4241-4244. PENG Chen, WANG Zhiqiang, LI Qijia, et al. Effect of zoledronic acid on proliferation and differentiation of osteoblasts as well as osteoprotegerin/nuclear factor-kappa B receptor agonist ligand mRNA expression[J]. Journal of Clinical Rehabilitative Tissue Engineering Research, 2009, 13(22):4241-4244.
[15] Farshdousti HM, Noruzinia M, Mortazavi Y, et al. Zoledrinic acid induces steoblastic differentiation of mesenchymal stem cells without change in hypomethylation status of OSTERIX promoter[J]. Cell J, 2012, 14(2):90-97.
[16] Fowlkes JL, Bunn RC, Liu L, et al. Runt-related transcription factor 2 (RUNX2) and RUNX2-related osteogenic genes are down-regulated throughout osteogenesis in type 1 diabetes mellitus[J]. Endocrinology, 2008, 149(4):1697-1704.
[17] Lee JH, Kim BG, Ahn JM, et al. Role of PI3K on the regulation of BMP2-induced beta-Catenin activation in human bone marrow stem cells[J]. Bone, 2010, 46(6):1522-1532.
[1] 张媛 李英敏 冯月秋 常彩云 潘华伟 王束玫. 血清脂联素水平与肥胖、胰岛素抵抗的关系探讨[J]. 山东大学学报(医学版), 2209, 47(6): 124-.
[2] 王梦星,薛付忠,杨帆. 基于多模态交叉注意力机制融合的1型糖尿病血糖浓度预测方法[J]. 山东大学学报 (医学版), 2025, 63(8): 41-50.
[3] 王雪梅,杨豪,宋洋,程世超,张婷婷,王艳春. 抗糖尿病药物与女性恶性肿瘤的因果关联:一项两样本孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(6): 67-77.
[4] 刘淋,王晓楠,杨雅溪,王江腾,李旭,周新丽,管庆波,张栩. 甘油三酯-葡萄糖指数与颅内动脉粥样硬化性狭窄的相关性[J]. 山东大学学报 (医学版), 2024, 62(8): 93-100.
[5] 许沛晨,李晓博,庄向华,娄能俊,吕丽,周玲雁,牟亚朋,宋玉文,陈诗鸿. 儿童Alstrom综合征2例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(3): 107-111.
[6] 王新起,徐晶晶,许旺旺,张洋,高进. 25(OH)D、IGF-I及焦虑、抑郁症状与门诊青少年精神障碍患者非自杀性自伤的关系[J]. 山东大学学报 (医学版), 2024, 62(12): 59-64.
[7] 张振伟,李佳,陈克明. IGF2BP2/m6A/ITGA5信号轴调控肾透明细胞增殖和迁移[J]. 山东大学学报 (医学版), 2022, 60(9): 74-84.
[8] 赵美茹,朱迪,刘淋,管庆波,张栩. 简易胰岛素抵抗指标与698例2型糖尿病患者发生高尿酸血症风险的关联[J]. 山东大学学报 (医学版), 2022, 60(12): 44-51.
[9] 牛群,石婧婧,符江. WNT5A基因对卵巢颗粒细胞胰岛素反应性和胰岛素抵抗的调控作用[J]. 山东大学学报 (医学版), 2021, 59(6): 57-63.
[10] 哈灵侠,殷婷,吴阳阳,黎维霞,杜玉冬. 多囊卵巢综合征患者中胰岛素抵抗与子宫内膜局部炎症因子及葡萄糖转运蛋白-4表达的相关性[J]. 山东大学学报 (医学版), 2021, 59(11): 41-47.
[11] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 1(7): 60-66.
[12] 徐红照,郝宗山, 沈德嫱,李朝苹,陈立勇. 核糖体蛋白S6激酶2沉默在乙醇诱导的心肌胰岛素抵抗中的作用[J]. 山东大学学报 (医学版), 2020, 58(4): 84-89.
[13] 徐焱焱,颜贝,王锐,王红燕. 经血间充质干细胞通过IGF-1信号通路改善小鼠卵巢早衰[J]. 山东大学学报 (医学版), 2020, 58(2): 13-20.
[14] 张星星,姜慧苗,马建梅,崔唯. IAA检测阴性的胰岛素自身免疫综合征1例[J]. 山东大学学报 (医学版), 2020, 58(2): 122-124.
[15] 吴成威,孙博实,周军德,蒋天明,迟强. 术前口服多糖溶液对结直肠癌患者术后胰岛素抵抗的关联性研究[J]. 山东大学学报 (医学版), 2019, 57(9): 48-53.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!