[1]杨其芬,邵秉一,杨德琴,等.miR-181a对骨质疏松小鼠骨髓贴壁基质细胞体外增殖活性的影响[J].第三军医大学学报,2015,37(19 ):1966-1971.
 Yang Qifen,Shao Bingyi,Yang Deqin,et al.Effect of miR-181a on proliferation of bone marrow mesenchymal stem cells from mouse osteoporosis model[J].J Third Mil Med Univ,2015,37(19 ):1966-1971.
点击复制

miR-181a对骨质疏松小鼠骨髓贴壁基质细胞体外增殖活性的影响(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
37卷
期数:
2015年第19期
页码:
1966-1971
栏目:
论著
出版日期:
2015-10-15

文章信息/Info

Title:
Effect of miR-181a on proliferation of bone marrow mesenchymal stem cells from mouse osteoporosis model
作者:
杨其芬邵秉一杨德琴郑玉琪
重庆医科大学附属口腔医院牙体牙髓科,口腔疾病与生物医学重庆市重点实验室,重庆市高校市级口腔生物医学工程重点实验室
Author(s):
Yang Qifen Shao Bingyi Yang Deqin Zheng Yuqi

Department of Endodontics, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Key Laboratory of Oral Biomedical Engineering of Chongqing Colleges and Universities, the Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China

关键词:
雌激素增殖miR-181a 骨髓贴壁基质细胞
Keywords:
estrogen proliferation miR-181a mesenchymal stem cells
分类号:
R-332; R329.25; R681.02
文献标志码:
A
摘要:

目的      探讨骨质疏松发生过程中miR-181a对骨髓贴壁基质细胞(mesenchymal stem cells, MSCs)增殖能力的影响。      方法      选用8周龄健康的20只雌性小鼠,并进行双侧卵巢切除(OVX组),建立雌性小鼠绝经后的骨质疏松模型。另选用同一周龄,体质量相近的20只健康小鼠行双侧卵巢附近脂肪组织部分切除,建立假手术组(Sham组)。2个月后Micro-CT检测2组小鼠松质骨中骨小梁微观结构参数及骨密度指标,MTT检测2组细胞增殖能力的差异。RT-PCR检测2组细胞中miR-181a的表达差异,上调(下调)细胞内miR-181a水平后MTT检测骨髓贴壁基质细胞增殖情况。      结果      Micro-CT显示Sham组与OVX组骨小梁微观结构参数及骨密度有显著差异(P<0.05)。MTT显示Sham组MSCs增殖能力高于OVX组(P<0.05)。RT-PCR显示Sham组中miR-181a较OVX组表达显著降低(P<0.05)。上调(下调)miR-181a后,MSCs增殖能力下降(上升)。成骨成脂能力检测发现OVX组MSCs成脂能力强于Sham组,而其成骨能力弱于Sham组(P<0.05)。      结论      雌激素缺乏所导致的骨质疏松症中,miR-181a高表达可抑制MSCs的增殖,可能是影响骨质疏松发病的重要因素之一。

Abstract:

Objective      To determine the effect of miR-181a on the proliferation of mouse bone mesenchymal stem cells (MSCs) derived from mouse model of osteoporosis (OP).       Methods      Animal model of OP was established by bilateral ovariectomy (OVX) in 20 8-week-old healthy female C57BL/6 mice, and the mice undergoing sham operation served as control. In 2 months later, micro-CT scanning was employed to detect the parameters of trabecular microstructure and the indicators of the bone mineral density of both groups. The mice were then sacrificed to isolate MSCs, which were then identified by flow cytometry for their phenotypes and by Alizarin red staining and Oil red 0 staining for osteogenic and adipogenic capacities. MTT assay was used to measure the proliferation capacity of the MSCs derived from 2 groups of mice. The mRNA expression of miR-181a was measured by RT-PCR. The proliferation of MSCs after up-regulating/down-regulating the expression of miR-181a was detected by MTT assay.       Results      The results of micro-CT scanning showed significant differences in the parameters of trabecular microstructure and the indicators of the bone mineral density between 2 groups (P<0.05). The proliferation capacity of MSCs was declined, and the expression of miR-181a was significantly increased in the cells from OVX group (P<0.05). Up-regulation/down-regulation of miR-181a resulted in significantly decreased/increased proliferation in MSCs. And the adipogenic capacity of MSCs was stronger in OVX group than in sham group, whereas the osteogenic capacity was weaker (P<0.05). MTT assay showed the proliferation capacity was better in the MSCs from sham operation group than from OVX group (P<0.05).       Conclusion      In the process of osteoporosis induced by estrogen deficiency, the high expression of miR-181a inhibits the proliferation of MSCs, which may play an important role in the pathogenesis of postmenopausal osteoporosis.

参考文献/References:

[1]Rachner T D, Khosla S, Hofbauer L C. Osteoporosis:  now and the future[J]. Lancet, 2011, 377(9773):  1276-1287.
[2]Teitelbaum S L. Stem cells and osteoporosis therapy[J]. Cell Stem Cell, 2010, 7(5): 553-554.
[3]Rodriguez J P, Rios S, Fernandez M,et al. Differential activation of ERK1,2 MAP kinase signaling pathway in mesenchymal stem cell from control and osteoporotic postmenopausal women[J].J Cell Biochem, 2004, 92(4): 745-754.
[4]Bartel D P. MicroRNAs:  genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2):  281-297.
[5]Khraiwesh B, Arif M A, Seumel G I,et al. Transcriptional control of gene expression by microRNAs[J]. Cell, 2010, 140(1): 111-122.
[6]Plasterk R H. micro RNAs in animal development[J]. Cell, 2006, 124(5): 877-881.
[7]Kosik K S. MicroRNAs and cellular phenotypy[J]. Cell, 2010, 143(1): 21-26.
[8]Stadler B M, Ruohola-Baker H. Small RNAs:  keeping stem cells in line[J]. Cell, 2008, 132(4): 563-566.
[9]Chen G, Zhu W, Shi D,et al. MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2[J]. Oncol Rep, 2010, 23(4): 997-1003.
[10]Li Q J, Chau J, Ebert P J,et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection[J]. Cell, 2007, 129(1): 147-161.
[11]Riggs B L, Khosla S, Melton L J 3rd. Sex steroids and the construction and conservation of the adult skeleton[J]. Endocr Rev, 2002, 23(3): 279-302.
[12]Hofer E L, La-Russa V, Honegger A E,et al. Alteration on the expression of IL-1, PDGF, TGF-beta, EGF, and FGF receptors and c-Fos and c-Myc proteins in bone marrow mesenchymal stroma cells from advanced untreated lung and breast cancer patients[J]. Stem Cells Dev, 2005, 14(5):  587-594.
[13]Kovacic N, Grcevic D, Katavic V,et al. Fas receptor is required for estrogen deficiency-induced bone loss in mice[J]. Lab Invest, 2010, 90(3): 402-413.
[14]Garcia-Moreno C, Catalan M P, Ortiz A,et al. Modulation of survival in osteoblasts from postmenopausal women[J]. Bone, 2004, 35(1): 170-177.
[15]Santiago-Mora R, Casado-Diaz A, De-Castro M D,et al. Oleuropein enhances osteoblastogenesis and inhibits adipogenesis:  the effect on differentiation in stem cells derived from bone marrow[J]. Osteoporos Int, 2011, 22(2):  675-684.
[16]Yang N, Wang G, Hu C,et al. Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis[J]. J Bone Miner Res, 2013, 28(3): 559-573.
[17]Wu X, Pang L, Lei W,et al. Inhibition of Sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling[J]. Cell Stem Cell, 2010, 7(5): 571-580.
[18]Liu G, Min H, Yue S,et al. Pre-miRNA loop nucleotides control the distinct activities of mir-181a-1 and mir-181c in early T cell development[J]. PLos One, 2008, 3(10):  e3529.
[19]Ebert P J, Jiang S, Xie J,et al. An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a[J]. Nat Immunol, 2009, 10(11): 1162-1169.
[20]Derynck R, Zhang Y E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling[J]. Nature, 2003, 425(6958): 577-584.
[21]Yoshimura A, Wakabayashi Y, Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta[J]. J Biochem, 2010, 147(6): 781-792.
[22]Liu, Wang Y, Fan H,et al. MicroRNA-181a regulates local immune balance by inhibiting proliferation and immunosuppressive properties of mesenchymal stem cells[J]. Stem Cells, 2012, 30(8): 1756-1770.
[23]Li H1, Xie H, Liu W,et al. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans[J]. J Clin Invest, 2009, 119(12): 3666-3677.
[24]Cohen A, Shmoish M, Levi L,et al. Alterations in micro-ribonucleic acid expression profiles reveal a novel pathway for estrogen regulation[J]. Endocrinology, 2008, 149(4): 1687-1696.
[25]Check-Hayden E. Thousands of proteins affected by miRNAs[J]. Nature, 2008, 454(7204):  562.

相似文献/References:

[1]李雪梅,罗淑娟,车亚玲,等.Rap1酶激动剂C3G对Ⅰ型卵巢癌细胞增殖和侵袭的影响[J].第三军医大学学报,2015,37(17):1715.
 Li Xuemei,Luo Shujuan,Che Yaling,et al.Effect of Rap1 activator C3G on proliferation and invasion in type Ⅰ ovarian cancer cells[J].J Third Mil Med Univ,2015,37(19 ):1715.
[2]朱宁生,张婧,曾晓华,等.BMP-4基因影响乳腺癌细胞增殖、凋亡和迁移能力涉及NF-κB途径[J].第三军医大学学报,2012,34(18):1910.
[3]黄士隋,史良会,黄广岩.RNA干扰下调LAT1表达对胃腺癌SGC-7901细胞增殖、侵袭、转移及细胞周期的影响[J].第三军医大学学报,2013,35(04):320.
 Huang Shisui,Shi Lianghui,Huang Guangyan.Effect of RNA interference targeting LAT1 on proliferation, migration and invasion of SGC7901 cells[J].J Third Mil Med Univ,2013,35(19 ):320.
[4]李维东,罗浩军,李振华,等.雌激素激活GPER-EGFR-ERK通路促进人乳腺癌SKBR-3细胞系增殖[J].第三军医大学学报,2012,34(22):2283.
 Li Weidong,Luo Haojun,Li Zhenhua,et al.Estrogen activates GPER-EGFR-ERK pathway to promote the proliferation of human breast cancer cell line SKBR-3[J].J Third Mil Med Univ,2012,34(19 ):2283.
[5]吴登艳,宋娇,董海良,等.mTOR信号通路介导黄芩苷抑制人结肠癌细胞的增殖[J].第三军医大学学报,2012,34(23):2399.
 Wu Dengyan,Song Jiao,Dong Hailiang,et al.mTOR signaling pathway mediates baicalin-inhibited proliferation in human colon cancer cell line HCT116[J].J Third Mil Med Univ,2012,34(19 ):2399.
[6]赖明广,姚君,王立生.HSP90抑制剂17-DMAG调控胰腺癌细胞PANC-1增殖及凋亡的初步研究[J].第三军医大学学报,2013,35(07):627.
 Lai Mingguang,Yao Jun,Wang Lisheng.Heat shock protein 90 inhibitor, 17-DMAG, suppresses proliferation and induces apoptosis in pancreatic cancer cells in vitro[J].J Third Mil Med Univ,2013,35(19 ):627.
[7]张晓辉,孙乃学,冯朝晖,等.ROCK-Ⅰ选择性抑制剂Y-27632对人Tenon囊成纤维细胞增殖、凋亡和黏附性的影响[J].第三军医大学学报,2013,35(01):38.
 Zhang Xiaohui,Sun Naixue,Feng Zhaohui,et al.Effect of Y-27632, a selective inhibitor of ROCK-I, on proliferation, apoptosis and adhesion of human ocular Tenon’s capsular fibroblasts[J].J Third Mil Med Univ,2013,35(19 ):38.
[8]李明,周永,糜漫天.染料木黄酮对人乳腺癌细胞株MDA-MB-453、MCF-7、MCF-7/HER2增殖能力的影响[J].第三军医大学学报,2008,30(17):1618.
 LI Ming,ZHOU Yong,MI Man-tian.Effect of genistein on proliferation of human breast cancer cell lines MDA-MB-453, MCF-7 and MCF-7/HER2[J].J Third Mil Med Univ,2008,30(19 ):1618.
[9]江永红,黄晶,邓昌明,等.吲哚-3-甲醇对大鼠动脉损伤后内膜增殖的影响[J].第三军医大学学报,2007,29(15):1504.
 JIANG Yong-hong,HUANG Jing,DENG Chang-ming,et al.Effects of indole-3-carbinol on neointimal hyperplasia of rat artery after balloon injury[J].J Third Mil Med Univ,2007,29(19 ):1504.
[10]吕伟,张超,郝嘉,等.shRNA沉默VEGF基因表达对大肠癌细胞生物学特性的影响[J].第三军医大学学报,2006,28(05):447.

更新日期/Last Update: 2015-09-28