中国医科大学学报

中国医科大学学报
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中国医科大学学报 ›› 2019, Vol. 48 ›› Issue (1): 44-47.doi: 10.12007/j.issn.0258-4646.2019.01.009

• 论著 • 上一篇    下一篇

骨质疏松小鼠骨组织中miR-21及Smad7的表达及其与骨密度的相关性

邓纯博, 刘林, 肖正俊, 阿良, 李洪秋   

  1. 沈阳医学院附属中心医院运动创伤骨科, 沈阳 110024
  • 收稿日期:2018-02-23 出版日期:2019-01-30 发布日期:2019-01-05
  • 通讯作者: 李洪秋 E-mail:hongqiulee@163.com
  • 作者简介:邓纯博(1982-),男,主治医师,硕士.
  • 基金资助:
    辽宁省自然科学基金(217011705-301);沈阳医学院科技基金(20141032)

Expression of miR-21 and Smad7 in the Osseous Tissues of Osteoporotic Mice and Its Correlation with Bone Mineral Density

DENG Chunbo, LIU Lin, XIAO Zhengjun, A Liang, LI Hongqiu   

  1. Department of Orthopaedics and Sports Medicine Surgery, The Central Hospital of Shenyang Medical College, Shenyang 110024, China
  • Received:2018-02-23 Online:2019-01-30 Published:2019-01-05

摘要: 目的 探讨去势骨质疏松模型骨组织中miR-21及其调控蛋白Smad7的含量变化,及其与骨密度的相关性。方法 将30只12周龄WTC57BL/6J雌性小鼠双侧卵巢切除,建立骨质疏松模型,应用免疫组化检测切除卵巢后不同时间点(0周、1周、2周、4周、6周及8周)骨组织中smad7的表达水平,实时PCR方法检测不同时间点骨组织中miR-21及靶基因smad7的mRNA水平,检测不同时间点股骨远端骨密度。结果 免疫组化研究发现,骨质疏松小鼠骨组织中Smad7随着时间的延长,其表达逐渐增强。实时PCR检测结果显示,骨组织中miR-21随着卵巢切除的时间逐渐延长,其表达逐渐降低,而Smad7随着卵巢切除的时间逐渐延长,表达逐渐增强。通过检测小鼠骨组织骨密度值并进行相关分析发现,随着时间的推移,小鼠的骨密度逐渐下降。结论 小鼠去势后,骨密度逐渐降低,miR-21表达与骨密度值呈正相关,而Smad7与骨密度值呈负相关。

关键词: 微小RNA, 骨质疏松, 成骨分化, miR-21, smad7, 骨密度

Abstract: Objective To investigate the changes in the expression levels of miR-21 and its regulatory proteins in bone tissues of osteoporotic mouse model,and its correlation with bone mineral density. Methods Thirty ovariectomized (ovx) female mice were randomly divided into six groups according to different observation time (0 week,1 week,2 weeks,4 weeks,6 weeks,and 8 weeks,respectively). Smad7 expression level in the tissues of the distal femur of these mice was immunohistochemically analyzed. Real time PCR was performed at different time points for detecting changes in the mRNA levels of miR-21 and Smad7 target genes in the bone tissue. Dual-energy X-ray absorptiometry (DXA) was used to measure the distal femoral bone density in mice of each group. Results Immunohistochemical study revealed that the expression of Smad7 in the bone tissue of osteoporostic mouse gradually increased over time. Real time PCR analysis showed that the expression of miR-21 gradually decreased,whereas the expression of Smad7 gradually increased. Over time,the bone density of mice gradually decreased,indicating that miR-21 was positively correlated with bone density,whereas Smad7 was negatively correlated with bone density. Conclusion Bone density of the osteoporotic mice gradually decreases. The expression of miR-21 is positively correlated with bone density,while that of Smad7 is negatively correlated with bone density.

Key words: microRNA, osteoporosis, osteogenesis, miR-21, smad7, bone mineral density

中图分类号: 

  • R589.5
[1] NICKLAS D,SAIZ L. Characterization of negative feedback network motifs in the TGF-β signaling pathway[J]. PLoS One,2013,8(12):e83531. DOI:10.1371/journal.pone.0083531.
[2] YAN X,LIN Z,CHEN F,et al. human BAMBI cooperates with Smad7 to inhibit transforming growth factor-β signaling[J]. J Biol Chem,2009,284(44):30097-30104. DOI:10.1074/jbc.M109.049304.
[3] YANG YJ,CHUANG CC,YANG HB,et al. Lactobacillus acidophilus ameliorates h. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways[J]. BMC Microbiol,2012,12:38. DOI:10.1186/1471-2180-12-38.
[4] CHEN G,DENG C,LI YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation[J]. Int J Biol Sci,2012,8(2):272-288. DOI:10.7150/ijbs.2929.
[5] LI H,YANG F,WANG Z,et al. MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7[J]. Mol Med Rep,2015,12(1):1561-1567. DOI:10.3892/mmr.2015.3497.
[6] 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. DOI:10.1002/jbmr.1798.
[7] ALEXY T,ROONEY K,WEBER M,et al. TNF-α alters the release and transfer of microparticle-encapsulated miRNAs from endothelial cells[J]. Physiol Genomics,2014,46(22):833-840. DOI:10.1152/physiolgenomics.00079.2014.
[8] DAMAVAND B,DERAKHSHANI S,SAEEDI N,et al. Intronic polymorphisms of the SMAD7 gene in association with colorectal cancer[J]. Asian Pac J Cancer Prev,2015,16(1):41-44.
[9] LAN HY. Transforming growth factor-β/Smad signaling in diabetic nephropathy[J]. Clin Exp Pharmacol Physio,2012,39(8):731-738. DOI:10.1111/j.1440-1681.2011.05663.x.
[10] LI Q,ZHANG D,WANG Y,et al. MiR-21/Smad7 signaling determines TGF-β1-induced CAF formation[J]. Sci Rep,2013,3:2038. DOI:10.1038/srep02038.
[11] YANO M,INOUE Y,TOBIMATSU T,et al. Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells[J]. Endocr J,2012,59(8):653-662.
[12] LI N,LEE WY,LIN SE,et al. Partial loss of Smad7 function impairs bone remodeling,osteogenesis and enhances osteoclastogenesis in mice[J]. Bone,2014,67:46-55. DOI:10.1016/j.bone.2014.06.033.
[13] ROBERTO VP,TIAGO DM,SILVA IA,et al. MiR-29a is an enhancer of mineral deposition in bone-derived systems[J]. Arch Biochem Biophys,2014,564:173-183.DOI:10.1016/j.abb.2014.09.006.
[14] WANG X,GUO B,LI Q,et al. MiR-214 targets ATF4 to inhibit bone formation[J]. Nat Med,2013,19(1):93-100. DOI:10.1038/nm.3026.
[15] ZHANG WB,ZHONG WJ,WANG L. A signal-amplification circuit between miR-218 and Wnt/β-catenin signal promotes human adipose tissue-derived stem cells osteogenic differentiation[J]. Bone,2014,58:59-66. DOI:10.1016/j.bone.2013.09.015.
[16] SATO MM,NASHIMOTO M,KATAGIRI T,et al. Bone morphogenetic protein-2 down-regulates miR-206 expression by blocking its maturation process[J]. Biochem Biophys Res Commun,2009,383(1):125-129. DOI:10.1016/j.bbrc.2009.03.142.
[17] QU B,XIA X,WU HH,et al. PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells[J]. Biochem Biophys Res Commun,2014,448(3):241-247. DOI:10.1016/j.bbrc.2014.04.091.
[18] HUANG CH,WEI JC,CHANG WC,et al.Higher expression of whole blood microRNA-21 in patients with ankylosing spondylitis associated with programmed cell death 4 mRNA expression and collagen cross-linked C-telopeptide concentration[J]. J Rheumatol,2014,41(6):1104-1111. DOI:10.3899/jrheum.130515.
[19] LI H,WANG Z,FU Q,et al. Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients[J]. Biomarkers,2014,19(7):553-556. DOI:10.3109/1354750X.2014.935957.
[20] YOSHIDA K,MATSUZAKI K. Differential regulation of TGF-β/Smad signaling in hepatic stellate cells between acute and chronic liver injuries[J]. Front Physiol,2012,3:53. DOI:10.3389/fphys.2012.00053.
[21] SHI Y,MASSAGUE J. Mechanisms of TGF-β signaling from cell membrane to the nucleus[J]. Cell,2003,113(6):685-700.
[22] BRIONES-ORTA MA,TECALCO-CRUZ AC,SOSA-GARROCHO M,et al. Inhibitory Smad7:emerging roles in health and disease[J]. Curr Mol Pharmacol,2011,4(2):141-153.
[23] LI Q. Inhibitory SMADs:potential regulators of ovarian function[J]. Biol Reprod,2015,92(2):50. DOI:10.1095/biolreprod.114.125203.
[24] YASUI T,KADONO Y,NAKAMURA M,et al. Regulation of RANKL-induced osteoclastogenesis by TGF-β through molecular interaction between Smad3 and Traf6[J]. J Bone miner Res,2011,26(7):1447-1456. DOI:10.1002/jbmr.357.
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