国际口腔医学杂志

国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (2): 138-145.doi: 10.7518/gjkq.2020018

• 牙周专栏 • 上一篇    下一篇

非编码RNA调控人牙周膜干细胞成骨向分化的研究进展

王润婷1,2,房付春1,2()   

  1. 1. 南方医科大学南方医院口腔科 广州 510515
    2. 南方医科大学口腔医学院 广州 510515
  • 收稿日期:2019-06-14 修回日期:2019-10-23 出版日期:2020-03-01 发布日期:2020-03-12
  • 通讯作者: 房付春
  • 作者简介:王润婷,医师,学士,Email： wrunting@163.com
  • 基金资助:
    国家自然科学基金(81600882)

Progress in research of non-coding RNAs in osteogenic differentiation of human periodontal ligament stem cells

Wang Runting1,2,Fang Fuchun1,2()   

  1. 1. Dept. of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    2. School of Stomatology, Southern Medical University, Guangzhou 510515, China
  • Received:2019-06-14 Revised:2019-10-23 Online:2020-03-01 Published:2020-03-12
  • Contact: Fuchun Fang
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81600882)

RichHTML

20

PDF (PC)

341

摘要：

牙周炎是一种常见的炎症性疾病,以牙齿支持结构的进行性损伤为特点,是我国成人牙齿丧失的主要原因。治疗牙周炎的目的不仅是通过控制炎症来阻止疾病发展,更重要的是获得牙周再生。人牙周膜干细胞具有成骨向分化潜能,有望在牙周组织修复再生的临床应用上发挥重要作用。非编码RNA（ncRNA）一般是指不编码蛋白质的RNA。伴随高通量检测技术的不断发展,发现了大量的种类丰富的ncRNA,其生物学功能也被不断揭示。越来越多证据显示,ncRNA在分子机制及细胞组织层面对疾病的发生、发展起重要调控作用,因此探索ncRNA调控机制可为牙周再生的研究提供新思路。本综述主要阐述了目前研究较多的几种ncRNA在人牙周膜干细胞成骨向分化中的调控机制。

关键词: 非编码RNA, 牙周再生, 牙周膜干细胞, 成骨向分化

Abstract:

Periodontitis is a common inflammatory disease that is characterised by progressive damage to dental supporting structure. Periodontitis is the main cause of tooth loss in adults in China. The aim of periodontal treatment is not only to control inflammation and prevent disease development but also to obtain periodontal regeneration. Human periodontal ligament stem cells (PDLSCs), which are capable of osteogenic differentiation, are expected to play important roles in clinical application of periodontal tissue repair and regeneration. Non-coding RNAs (ncRNAs) generally refer to RNAs that do not encode proteins. The continuous development of high-throughput detection techniques has allowed the identification of a large number of ncRNAs and their biological functions. Increasing numbers of ncRNAs have been reported to function in the pathogenesis of diseases at molecular and cellular levels. Therefore, research on ncRNAs can provide new insights into periodontal regeneration. This review focuses on the regulatory mechanism of several ncRNAs in the osteogenic differentiation of human PDLSCs.

Key words: non-coding RNA, periodontal regeneration, periodontal ligament stem cell, osteogenic differentiation

中图分类号: 

  • Q756

表 1

ncRNA参与牙周膜干细胞成骨分化调控"

名称 类型 诱导方式 调控水平 调控作用 可能的靶基因或作用通路 文献
miR-24-3p miRNA 矿化 转录后水平 抑制 靶向作用Smad5 [15]
miR-21 miRNA 矿化 转录后水平 抑制 靶向作用Smad5 [16]
矿化 转录后水平 抑制 miR-21/Spry1调控轴介导TNF-α对牙周膜干细胞的抑制成骨 [17]
作用
剪切力 转录后水平 抑制 靶向作用ACVR2B [29]
miR-203 miRNA 矿化 转录后水平 抑制 靶向作用RUNX2 [18]
miR-1305 miRNA 矿化 转录后水平 抑制 靶向作用RUNX2 [19]
miR-218 miRNA 矿化 转录后水平 抑制 靶向作用RUNX2 [20]
miR-214 miRNA 矿化 转录后水平 抑制 靶向作用ATF4 [21]
矿化 转录后水平 抑制 通过靶向作用β-连环蛋白1调节Wnt/β-连环蛋白信号通路 [22]
miR-17 miRNA 矿化 转录后水平 抑制 通过靶向作用TCF3调节经典Wnt信号通路 [23-24]
miR-31 miRNA 矿化 转录后水平 抑制 靶向作用Satb2 [25]
miR-200c miRNA 矿化 转录后水平 促进 抑制IL-6、IL-8和CCL-5 [26]
miR-543 miRNA 矿化 转录后水平 促进 靶向作用TOB2 [27]
miR-22 miRNA 矿化 转录后水平 促进 抑制HDAC6 [28]
名称 类型 诱导方式 调控水平 调控作用 可能的靶基因或作用通路 文献
MEG3 lncRNA 矿化 转录水平 抑制 与hnRNPK结合,影响BMP2转录 [37]
ANCR lncRNA 矿化 转录水平 抑制 通过调控GSK3β的表达抑制Wnt/β-连环蛋白信号通路,下调 [38]
RUNX2
矿化 转录后水平 抑制 ANCR/miR-758/Notch2 [40]
TUG1 lncRNA 矿化 转录水平 促进 Lin28A蛋白作为TUG1的RBP形成正性调控网络 [36]
PCAT1 lncRNA 矿化 转录后水平 促进 PCAT1/miR-106a-5p/BMP2 PCAT1/miR-106a-5p/E2F5前馈调 [41]
节网络
HIF1A-AS2 lncRNA 缺氧 转录后水平 促进 通过碱基配对与HIF-1α形成双链RNA,提高蛋白质翻译水平 [42]
CDR1 circRNA 矿化 转录后水平 促进 竞争性结合miR-7,使GDF5上调、Smad1/5/8及p38MAPK [46]
磷酸化
[1] Pihlstrom BL, Michalowicz BS, Johnson NW . Perio-dontal diseases[J]. Lancet, 2005,366(9499):1809-1820.
[2] 王兴 . 第四次全国口腔健康流行病学调查报告[M]. 北京: 人民卫生出版社, 2018: 25-34.
Wang X. The forth national oral health epidemiolo-gical survey[M]. Beijing: People’s Medical Publishing House, 2018: 25-34.
[3] Graziani F, Karapetsa D, Mardas N , et al. Surgical treatment of the residual periodontal pocket[J]. Pe-riodontol 2000, 2018,76(1):150-163.
[4] Vaquette C, Pilipchuk SP, Bartold PM , et al. Tissue engineered constructs for periodontal regeneration: current status and future perspectives[J]. Adv Heal-thc Mater, 2018,7(21):e1800457.
[5] Iviglia G, Kargozar S, Baino F . Biomaterials, current strategies, and novel nano-technological approaches for periodontal regeneration[J]. J Funct Biomater, 2019,10(1). doi: 10.3390/jfb10010003.
[6] Seo BM, Miura M, Gronthos S , et al. Investigation of multipotent postnatal stem cells from human pe-riodontal ligament[J]. Lancet, 2004,364(9429):149-155.
[7] Hernández-Monjaraz B, Santiago-Osorio E, Monroy-García A , et al. Mesenchymal stem cells of dental origin for inducing tissue regeneration in perio-dontitis: a mini-review[J]. Int J Mol Sci, 2018,19(4). doi: 10.3390/ijms19040944.
[8] International Human Genome Sequencing Consor-tium. Finishing the euchromatic sequence of the human genome[J]. Nature, 2004,431(7011):931-945.
[9] Ponting CP, Belgard TG . Transcribed dark matter: meaning or myth[J]. Hum Mol Genet, 2010,19(R2):R162-R168.
[10] Kaur P, Liu F, Tan JR , et al. Non-coding RNAs as potential neuroprotectants against ischemic brain injury[J]. Brain Sci, 2013,3(1):360-395.
[11] Vemuganti R . All’s well that transcribes well: non-coding RNAs and post-stroke brain damage[J]. Neu-rochem Int, 2013,63(5):438-449.
[12] Liu B, Li J, Cairns MJ . Identifying miRNAs, targets and functions[J]. Brief Bioinform, 2014,15(1):1-19.
[13] Vidigal JA, Ventura A . The biological functions of miRNAs: lessons from in vivo studies[J]. Trends Cell Biol, 2015,25(3):137-147.
[14] Hao Y, Ge Y, Li J , et al. Identification of MicroRNAs by microarray analysis and prediction of target genes involved in osteogenic differentiation of human periodontal ligament stem cells[J]. J Periodontol, 2017,88(10):1105-1113.
[15] Li Z, Sun Y, Cao S , et al. Downregulation of miR-24-3p promotes osteogenic differentiation of human periodontal ligament stem cells by targeting SMAD family member 5[J]. J Cell Physiol, 2019,234(5):7411-7419.
[16] Wei F, Yang S, Guo Q , et al. MicroRNA-21 regulates osteogenic differentiation of periodontal ligament stem cells by targeting Smad5[J]. Sci Rep, 2017,7(1):16608.
[17] Yang N, Li Y, Wang G , et al. Tumor necrosis factor-α suppresses adipogenic and osteogenic differentiation of human periodontal ligament stem cell by inhibi-ting miR-21/Spry1 functional axis[J]. Differentiation, 2017,97:33-43.
[18] 冯保静, 赵西博, 郝志红 , 等. miR-203靶向RUNX2对牙周膜干细胞成骨向分化能力的调控作用[J]. 口腔颌面修复学杂志, 2019,20(1):44-48.
Feng BJ, Zhao XB, Hao ZH , et al. Study on effect of miR-203 for targeting RUNX2 on osteogenic dif-ferentiation of human periodontal ligament stem cells[J]. Chin J Prosthodont, 2019,20(1):44-48.
[19] Chen Z, Liu HL . Restoration of miR-1305 relieves the inhibitory effect of nicotine on periodontal liga-ment-derived stem cell proliferation, migration, and osteogenic differentiation[J]. J Oral Pathol Med, 2017,46(4):313-320.
[20] Gay I, Cavender A, Peto D , et al. Differentiation of human dental stem cells reveals a role for micro-RNA-218[J]. J Periodontal Res, 2014,49(1):110-120.
[21] Yao S, Zhao W, Ou Q , et al. MicroRNA-214 sup-presses osteogenic differentiation of human perio-dontal ligament stem cells by targeting ATF4[J]. Stem Cells Int, 2017,2017:3028647.
[22] Cao F, Zhan J, Chen X , et al. miR-214 promotes periodontal ligament stem cell osteoblastic differen-tiation by modulating Wnt/β-catenin signaling[J]. Mol Med Rep, 2017,16(6):9301-9308.
[23] Liu W, Liu Y, Guo T , et al. TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments[J]. Cell Death Dis, 2013,4:e539.
[24] Liu Y, Liu W, Hu C , et al. MiR-17 modulates osteo-genic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from perio-dontal ligaments of patients with periodontitis[J]. Stem Cells, 2011,29(11):1804-1816.
[25] Zhen L, Jiang X, Chen Y , et al. MiR-31 is involved in the high glucose-suppressed osteogenic differentia-tion of human periodontal ligament stem cells by targeting Satb2[J]. Am J Transl Res, 2017,9(5):2384-2393.
[26] Hong L, Sharp T, Khorsand B , et al. MicroRNA-200c represses IL-6, IL-8, and CCL-5 expression and enhances osteogenic differentiation[J]. PLoS One, 2016,11(8):e0160915.
[27] Ge Y, Li J, Hao Y , et al. MicroRNA-543 functions as an osteogenesis promoter in human periodontal ligament-derived stem cells by inhibiting transducer of ERBB2, 2[J]. J Periodontal Res, 2018,53(5):832-841.
[28] Yan GQ, Wang X, Yang F , et al. MicroRNA-22 promoted osteogenic differentiation of human perio-dontal ligament stem cells by targeting HDAC6[J]. J Cell Biochem, 2017,118(7):1653-1658.
[29] Wei FL, Wang JH, Ding G , et al. Mechanical force-induced specific MicroRNA expression in human periodontal ligament stem cells[J]. Cells Tissues Organs, 2014,199(5/6):353-363.
[30] Dragomir MP, Knutsen E, Calin GA . SnapShot: unconventional miRNA functions[J]. Cell, 2018, 174(4): 1038-1038.e1.
[31] Iyer MK, Niknafs YS, Malik R , et al. The landscape of long noncoding RNAs in the human transcriptome[J]. Nat Genet, 2015,47(3):199-208.
[32] Zheng Y, Li X, Huang Y , et al. Time series clustering of mRNA and lncRNA expression during osteogenic differentiation of periodontal ligament stem cells[J]. Peer J, 2018,6:e5214.
[33] Gu X, Li M, Jin Y , et al. Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation[J]. BMC Genet, 2017,18(1):100.
[34] Qu Q, Fang F, Wu B , et al. Potential role of long non-coding RNA in osteogenic differentiation of human periodontal ligament stem cells[J]. J Perio-dontol, 2016,87(7):e127-e137.
[35] Huang Y, Zhang Y, Li X , et al. The long non-coding RNA landscape of periodontal ligament stem cells subjected to compressive force[J]. Eur J Orthod, 2019,41(4):333-342.
[36] He Q, Yang S, Gu X , et al. Long noncoding RNA TUG1 facilitates osteogenic differentiation of perio-dontal ligament stem cells via interacting with Lin-28A[J]. Cell Death Dis, 2018,9(5):455.
[37] Liu Y, Zeng X, Miao J , et al. Upregulation of long noncoding RNA MEG3 inhibits the osteogenic dif-ferentiation of periodontal ligament cells[J]. J Cell Physiol, 2019,234(4):4617-4626.
[38] Jia Q, Jiang W, Ni L . Down-regulated non-coding RNA (lncRNA-ANCR) promotes osteogenic dif-ferentiation of periodontal ligament stem cells[J]. Arch Oral Biol, 2015,60(2):234-241.
[39] Wang L, Wu F, Song Y , et al. Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients[J]. Cell Death Dis, 2016,7(8):e2327.
[40] Peng W, Deng W, Zhang J , et al. Long noncoding RNA ANCR suppresses bone formation of perio-dontal ligament stem cells via sponging miRNA-758[J]. Biochem Biophys Res Commun, 2018,503(2):815-821.
[41] Jia B, Qiu X, Chen J , et al. A feed-forward regulatory network lncPCAT1/miR-106a-5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells[J]. J Cell Physiol, 2019,234(11):19523-19538.
[42] Chen D, Wu L, Liu L , et al. Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia[J]. Int J Mol Med, 2017,40(5):1529-1536.
[43] Zhu L, Xu PC . Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression[J]. Biochem Biophys Res Commun, 2013,432(4):612-617.
[44] Zhang J, Hao X, Yin M , et al. Long non-coding RNA in osteogenesis: a new world to be explored[J]. Bone Joint Res, 2019,8(2):73-80.
[45] Qu S, Yang X, Li X , et al. Circular RNA: a new star of noncoding RNAs[J]. Cancer Lett, 2015,365(2):141-148.
[46] Li X, Zheng Y, Zheng Y , et al. Circular RNA CDR1as regulates osteoblastic differentiation of periodontal ligament stem cells via the miR-7/GDF5/SMAD and p38 MAPK signaling pathway[J]. Stem Cell Res Ther, 2018,9(1):232.
[47] Wang H, Feng C, Jin Y , et al. Identification and characterization of circular RNAs involved in me-chanical force-induced periodontal ligament stem cells[J]. J Cell Physiol, 2019,234(7):10166-10177.
[48] Zhang Y, Zhang XO, Chen T , et al. Circular intronic long noncoding RNAs[J]. Mol Cell, 2013,51(6):792-806.
[49] Ashwal-Fluss R, Meyer M, Pamudurti NR , et al. circRNA biogenesis competes with pre-mRNA splicing[J]. Mol Cell, 2014,56(1):55-66.
[50] Du WW, Yang W, Liu E , et al. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2[J]. Nucleic Acids Res, 2016,44(6):2846-2858.
[1] 周金阔,张晋弘,史晓晶,刘广顺,姜磊,刘倩峰. 长链非编码RNA小核仁RNA宿主基因22调控微小RNA-27b-3p对口腔鳞状细胞癌细胞增殖、侵袭和迁移的影响[J]. 国际口腔医学杂志, 2024, 51(1): 52-59.
[2] 杨梦瑶,高现灵,邓淑丽. 静电纺丝纳米纤维在牙周再生中的应用[J]. 国际口腔医学杂志, 2023, 50(1): 10-18.
[3] 张静怡,李丹薇,孙宇,雷雅燕,刘涛,龚瑜. 复合树脂及复合体对成骨细胞毒性及成骨向分化的影响[J]. 国际口腔医学杂志, 2022, 49(4): 412-419.
[4] 蔡超莹,陈学鹏,胡济安. 外泌体复合支架用于口腔组织工程的研究进展[J]. 国际口腔医学杂志, 2022, 49(4): 489-496.
[5] 洪娅娅,陈学鹏,姒蜜思. 非编码RNA调控牙囊干细胞成骨分化的研究进展[J]. 国际口腔医学杂志, 2022, 49(3): 263-271.
[6] 巩靖蕾,黄艳梅,王军. 多相支架在牙周再生领域的研究进展[J]. 国际口腔医学杂志, 2021, 48(5): 563-569.
[7] 汪是琦,常雅琴,陈斌,谭葆春,泥艳红. 植骨术与植骨联用屏障膜在牙周再生治疗中临床疗效对比的系统评价与Meta分析[J]. 国际口腔医学杂志, 2020, 47(6): 644-651.
[8] 杨叶青,陈明,吴补领. 环状非编码RNA在间充质干细胞成骨向分化中作用的研究进展[J]. 国际口腔医学杂志, 2020, 47(3): 257-262.
[9] 刘俊圻,陈艺尹,杨文宾. RNA腺嘌呤6-甲基化修饰调控骨髓间充质干细胞成骨向分化的研究进展[J]. 国际口腔医学杂志, 2020, 47(3): 263-269.
[10] 吴晓楠,马宁,侯建霞. 不同干细胞来源外泌体在牙周再生领域的研究进展[J]. 国际口腔医学杂志, 2020, 47(2): 146-151.
[11] 余晓宏,刘屿,曾莲,杨艳玲,王洲,李卫. 釉基质衍生物对人牙周膜干细胞成骨分化的影响[J]. 国际口腔医学杂志, 2020, 47(1): 24-31.
[12] 张凯莹,房付春,吴补领. 非编码RNA在牙源性干细胞成牙本质向分化中作用的研究进展[J]. 国际口腔医学杂志, 2019, 46(5): 540-545.
[13] 李媛媛,程斌,王韵. 长链非编码RNA lnc-p26090对口腔鳞状细胞癌细胞糖酵解及增殖的影响[J]. 国际口腔医学杂志, 2018, 45(6): 628-634.
[14] 王伊婷,何永文. 口腔鳞状细胞癌相关长链非编码RNA调控肿瘤细胞上皮-间充质转化的研究进展[J]. 国际口腔医学杂志, 2018, 45(6): 635-639.
[15] 韩曈曈,陈乔尔,朱友明. p53相关长链非编码RNA及其与口腔癌的关系[J]. 国际口腔医学杂志, 2018, 45(5): 597-602.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[8] 费晓露,丁一,徐屹. 牙周可疑致病菌对口腔黏膜上皮的粘附和侵入[J]. 国际口腔医学杂志, 2005, 32(06): 452 -454 .
[9] 赵兴福,黄晓晶. 变形链球菌蛋白组学研究进展[J]. 国际口腔医学杂志, 2008, 35(S1): .
[10] 庞莉苹,姚江武. 抛光和上釉对陶瓷表面粗糙度、挠曲强度及磨损性能的影响[J]. 国际口腔医学杂志, 2008, 35(S1): .