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浙江大学学报（医学版）
浙江大学学报（医学版）  2016, Vol. 45 Issue (2): 170-178    DOI: 10.3785/j.issn.1008-9292.2016.03.10
运动系统再生医学专题     
微RNA:一类新的椎间盘退变调控因子
王程1,2, 王文军2, 杨威2, 于小华3, 晏怡果2, 张健4, 姜志胜1
1. 南华大学心血管疾病研究所 动脉硬化学湖南省重点实验室, 湖南 衡阳 421001;
2. 南华大学附属第一医院脊柱外科, 湖南 衡阳 421001;
3. 南华大学生命科学研究中心, 湖南 衡阳 421001;
4. 南华大学附属第一医院手显微外科, 湖南 衡阳 421001
MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration
WANG Cheng1,2, WANG Wenjun2, YANG Wei2, YU Xiaohua3, YAN Yiguo2, ZHANG Jian4, JIANG Zhisheng1
1. Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, China;
2. Department of Spine Surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China;
3. Life Science Research Center, University of South China, Hengyang 421001, China;
4. Department of Hand and Micro-surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China
全文: PDF(1047 KB)  
摘要: 

椎间盘退变(IDD)是引起椎间盘退行性疾病的主要原因之一,其导致的下腰痛严重影响患者生活质量。目前,临床上针对IDD的治疗手段主要以缓解临床症状为主,而不是从其病理机制入手,尚缺乏有效的生物学治疗手段。微RNA(miRNA)是一种在转录后水平调控基因表达的内源性单链非编码小RNA,参与调控多种生物学过程,如脂类代谢和细胞凋亡、分化及器官发育。研究表明,miRNA在退变的椎间盘组织中呈高表达或低表达,参与IDD的多种病理过程,包括髓核细胞增生和凋亡、细胞外基质合成、炎症反应及软骨终板退变。本文总结了miRNA在退变椎间盘组织中的表达谱及其在IDD发生发展中的作用。随着对miRNA研究的深入,miRNA可能成为IDD生物学治疗的新策略。
关键词 ： 微RNAs,  基因表达,  椎间盘/病理学,  细胞外基质,  细胞增殖,  细胞凋亡,  炎症/病因学,  椎间盘移位/病理学,  综述    
Abstract：

Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNA molecules, which regulate the gene expression at the post-transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease.
Key words： MicroRNAs    Gene expression    Intervertebral disk/pathology    Extracellular matrix    Cell proliferation    Apoptosis    Inflammation/etiology    Intervertebral disk displacement/pathology    Review
收稿日期: 2015-10-12     
CLC:  R68  
基金资助:

国家自然科学基金(31400802);湖南省自然科学基金(2015JJ5003)
通讯作者: 姜志胜(1965-),男,博士,教授,从事心血管及椎间盘疾病的分子生物学机制研究及临床应用;E-mail:zsjiang2005@163.com     E-mail: zsjiang2005@163.com
作者简介: 王程(1978-),男,博士研究生,从事椎间盘退变的基础研究;E-mail:2598166583@qq.com
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引用本文:

王程 等. 微RNA:一类新的椎间盘退变调控因子[J]. 浙江大学学报（医学版）, 2016, 45(2): 170-178.
WANG Cheng, WANG Wenjun, YANG Wei, YU Xiaohua, YAN Yiguo, ZHANG Jian, JIANG Zhisheng. MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration. Journal of ZheJiang University(Medical Science), 2016, 45(2): 170-178.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.03.10      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I2/170

[1] VOS T, FLAXMAN A D, NAGHAVI M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010[J]. Lancet, 2012,380(9859):2163-2196.
[2] WEBER K T, JACOBSEN T D, MAIDHOF R, et al. Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics[J]. Curr Rev Musculoskelet Med, 2015,8(1):18-31.
[3] KABIR S M, GUPTA S R, CASEY A T. Lumbar interspinous spacers: a systematic review of clinical and biomechanical evidence[J]. Spine (Phila Pa 1976), 2010,35(25):E1499-E1506.
[4] TAHER F, ESSIG D, LEBL D R, et al. Lumbar degenerative disc disease: current and future concepts of diagnosis and management[J]. Adv Orthop, 2012,2012: 970752.
[5] MIRZAMOHAMMADI F, PAPAIOANNOU G, KOBAYASHI T. MicroRNAs in cartilage development, homeostasis, and disease[J]. Curr Osteoporos Rep, 2014,12(4):410-419.
[6] LI Z, YU X, SHEN J, et al. MicroRNA in intervertebral disc degeneration[J]. Cell Prolif, 2015,48(3):278-283.
[7] PEREIRA D R, SILVA-CORREIA J, OLIVEIRA J M, et al. Hydrogels in acellular and cellular strategies for intervertebral disc regeneration[J]. J Tissue Eng Regen Med, 2013,7(2):85-98.
[8] WANG S Z, RUI Y F, LU J, et al. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies[J]. Cell Prolif, 2014,47(5):381-390.
[9] WEILER C, NERLICH A G, SCHAAF R, et al. Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc[J]. Eur Spine J, 2010,19(10):1761-1770.
[10] DUNCAN N A. Cell deformation and micromechanical environment in the intervertebral disc[J]. J Bone Joint Surg Am, 2006,88 Suppl 2: 47-51.
[11] BLANQUER S B, GRIJPMA D W, POOT A A. Delivery systems for the treatment of degenerated intervertebral discs[J]. Adv Drug Deliv Rev, 2015,84: 172-187.
[12] VERGROESEN P P, KINGMA I, EMANUEL K S, et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle[J]. Osteoarthritis Cartilage, 2015,23(7):1057-1070.
[13] KEPLER C K, PONNAPPAN R K, TANNOURY C A, et al. The molecular basis of intervertebral disc degeneration[J]. Spine J, 2013,13(3):318-330.
[14] WANG W J, YU X H, WANG C, et al. MMPs and ADAMTSs in intervertebral disc degeneration[J]. Clin Chim Acta, 2015,448: 238-246.
[15] YANG W, YU X H, WANG C, et al. Interleukin-1beta in intervertebral disk degeneration[J]. Clin Chim Acta, 2015,450: 262-272.
[16] SMALL E M, OLSON E N. Pervasive roles of microRNAs in cardiovascular biology[J]. Nature, 2011,469(7330):336-342.
[17] WU C, TIAN B, QU X, et al. MicroRNAs play a role in chondrogenesis and osteoarthritis (review)[J]. Int J Mol Med, 2014,34(1):13-23.
[18] HONG E, REDDI A H. MicroRNAs in chondrogenesis, articular cartilage, and osteoarthritis: implications for tissue engineering[J]. Tissue Eng Part B Rev, 2012,18(6):445-453.
[19] SHANG J, LIU H, ZHOU Y. Roles of microRNAs in prenatal chondrogenesis, postnatal chondrogenesis and cartilage-related diseases[J]. J Cell Mol Med, 2013,17(12):1515-1524.
[20] GUO H, INGOLIA N T, WEISSMAN J S, et al. Mammalian microRNAs predominantly act to decrease target mRNA levels[J]. Nature, 2010,466(7308):835-840.
[21] BARTEL D P. MicroRNAs: target recognition and regulatory functions[J]. Cell, 2009,136(2):215-233.
[22] HU P, FENG B, WANG G, et al. Microarray based analysis of gene regulation by microRNA in intervertebral disc degeneration[J]. Mol Med Rep, 2015,12(4):4925-4930.
[23] ZHAO B, YU Q, LI H, et al. Characterization of microRNA expression profiles in patients with intervertebral disc degeneration[J]. Int J Mol Med, 2014,33(1):43-50.
[24] JI M L, LU J, SHI P L, et al. Dysregulated miR-98 contributes to extracellular matrix degradation by targeting IL-6/STAT3 signalling pathway in human intervertebral disc degeneration[J]. J Bone Miner Res, 2015,31(4):900-909.
[25] LI H R, CUI Q, DONG Z Y, et al. Downregulation of miR-27b is involved in loss of type Ⅱ collagen by directly targeting matrix metalloproteinase 13 (MMP13) in human intervertebral disc degeneration[J]. Spine (Phila Pa 1976), 2016,41(3):E116-E123.
[26] OHRT-NISSEN S, DOSSING K B, ROSSING M, et al. Characterization of miRNA expression in human degenerative lumbar disks[J]. Connect Tissue Res, 2013,54(3):197-203.
[27] JI M L, ZHANG X J, SHI P L, et al. Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14[J]. J Mol Med (Berl), 2016,94(4):457-468.
[28] XU Y Q, ZHANG Z H, ZHENG Y F, et al. Dysregulated miR-133a mediates loss of type Ⅱ collagen by directly targeting matrix metalloproteinase 9 (MMP9) in human intervertebral disc degeneration[J]. Spine (Phila Pa 1976), 2015. [Epub ahead of print]
[29] DING F, SHAO Z W, XIONG L M. Cell death in intervertebral disc degeneration[J]. Apoptosis, 2013,18(7):777-785.
[30] WANG T, LI P, MA X, et al. MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-alpha-induced apoptosis by targeting JunD[J]. Biochimie, 2015,115: 1-7.
[31] LIU G, CAO P, CHEN H, et al. MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K[J]. PLoS One, 2013,8(9):e75251.
[32] WANG H Q, YU X D, LIU Z H, et al. Deregulated miR-155 promotes fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3[J]. J Pathol, 2011,225(2):232-242.
[33] PRATSINIS H, CONSTANTINOU V, PAVLAKIS K, et al. Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways[J]. J Orthop Res, 2012,30(6):958-964.
[34] DONG S, YANG B, GUO H, et al. MicroRNAs regulate osteogenesis and chondrogenesis[J]. Biochem Biophys Res Commun, 2012,418(4):587-591.
[35] 余 强,李浩鹏,郭 雄. MicroRNA在软骨损伤退变中作用机制的研究[J]. 中国骨伤,2012,25(6):530-534. YU Qiang, LI Haopeng, GUO Xiong. The mechanism advance of microRNA in cartilage injury and degeneration[J]. China Journal of Orthapaedics and Traumatology, 2012,25(6):530-534.(in Chinese)
[36] LIU H, HUANG X, LIU X, et al. miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling[J]. Int J Mol Sci, 2014,15(3):4007-4018.
[37] YU X, LI Z, SHEN J, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration[J]. PLoS One, 2013,8(12):e83080.
[38] WANG F, SHI R, CAI F, et al. Stem cell approaches to intervertebral disc regeneration: obstacles from the disc microenvironment[J]. Stem Cells Dev, 2015,24(21):2479-2495.
[39] HE F, PEI M. Rejuvenation of nucleus pulposus cells using extracellular matrix deposited by synovium-derived stem cells[J]. Spine (Phila Pa 1976), 2012,37(6):459-469.
[40] YAN N, YU S, ZHANG H, et al. Lumbar disc degeneration is facilitated by miR-100-mediated FGFR3 suppression[J]. Cell Physiol Biochem, 2015,36(6):2229-2236.
[41] JING W, JIANG W. MicroRNA-93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells[J]. Cell Prolif, 2015,48(3):284-292.
[42] GU S X, LI X, HAMILTON J L, et al. MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc[J]. Gene, 2015,555(2):80-87.
[43] MOLINOS M, ALMEIDA C R, CALDEIRA J, et al. Inflammation in intervertebral disc degeneration and regeneration[J]. J R Soc Interface, 2015,12(104):20141191.
[44] PENG Y, LV F J. Symptomatic versus asymptomatic intervertebral disc degeneration: is inflammation the key?[J]. Crit Rev Eukaryot Gene Expr, 2015,25(1):13-21.
[45] NEIDLINGER-WILKE C, BOLDT A, BROCHHAUSEN C, et al. Molecular interactions between human cartilaginous endplates and nucleus pulposus cells: a preliminary investigation[J]. Spine (Phila Pa 1976), 2014,39(17):1355-1364.
[46] 程细高, 贾惊宇, 吴添龙, 等. miR-140-5P参与调控颈椎软骨终板退变[J]. 南昌大学学报(医学版), 2014(5):1-5. CHENG Xigao, JIA Jingyu, WU Tianlong, et al. Involvement of miR-140-5P in cartilaginous endplate degeneration in cervical vertebrate[J]. Journal of Nanchang University(Medical Sciences), 2014(5):1-5.(in Chinese)
[47] YU C, CHEN W P, WANG X H. MicroRNA in osteoarthritis[J]. J Int Med Res, 2011,39(1):1-9.
[48] PIERREFITE-CARLE V, SANTUCCI-DARMANIN S, BREUIL V, et al. Autophagy in bone: self-eating to stay in balance[J]. Ageing Res Rev, 2015,24(Pt B):206-217.
[49] XU K, CHEN W, WANG X, et al. Autophagy attenuates the catabolic effect during inflammatory conditions in nucleus pulposus cells, as sustained by NF-kappaB and JNK inhibition[J]. Int J Mol Med, 2015,36(3):661-668.
[50] JIANG L, YUAN F, YIN X, et al. Responses and adaptations of intervertebral disc cells to microenvironmental stress: a possible central role of autophagy in the adaptive mechanism[J]. Connect Tissue Res, 2014,55(5-6):311-321.
[51] SU M, WANG J, WANG C, et al. MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the p27/CDK2/mTOR axis[J]. Cell Death Differ, 2015,22(6):986-999.
[52] ZHANG X, SHI H, LIN S, et al. MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy[J]. Oncol Rep, 2015,34(3):1557-1564.
[53] WANG I K, SUN K T, TSAI T H, et al. MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury[J]. Life Sci, 2015,136: 133-141.
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