国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (3): 263-269.doi: 10.7518/gjkq.2020033

• 间充质干细胞专栏 • 上一篇    下一篇

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

刘俊圻,陈艺尹,杨文宾()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心四川大学华西口腔医院口腔颌面外科 成都 610041
  • 收稿日期:2019-08-13 修回日期:2019-11-29 出版日期:2020-05-01 发布日期:2020-05-08
  • 通讯作者: 杨文宾 E-mail:yangwenbinkq@163.com
  • 作者简介:刘俊圻,学士,Email:609591179@qq.com
  • 基金资助:
    四川大学华西口腔医院探索与研发项目(RD-02-201907)

Research progress on N6-methyladenosine for regulating the osteogenic differentiation of bone marrow mesenchymal stem cells

Liu Junqi,Chen Yiyin,Yang Wenbin()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2019-08-13 Revised:2019-11-29 Online:2020-05-01 Published:2020-05-08
  • Contact: Wenbin Yang E-mail:yangwenbinkq@163.com
  • Supported by:
    Research and Development Foundation of West China Hospital of Stomatology, Sichuan University(RD-02-201907)

摘要:

RNA腺嘌呤6-甲基化修饰是真核生物信使RNA和非编码RNA上最为常见的一种表观遗传修饰,对于真核生物多项生命活动的调控起着至关重要的作用。近来的研究发现,RNA腺嘌呤6-甲基化修饰在骨髓间充质干细胞的分化,尤其是成骨向分化上,扮演着十分重要的角色。本文通过对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相关研究加以总结,以期为后续基础研究以及临床应用提供新的思路。

关键词: 6-甲基腺嘌呤, RNA修饰, 成骨向分化, 间充质干细胞

Abstract:

RNA N6-methylation of adenosine is the most prevalent epigenetic modification of messenger and noncoding RNAs in eukaryotes and plays an important role in various biological processes. Recent studies demonstrated that RNA N6-methyladenosine has profound effect on bone marrow mesenchymal stem cell differentiation, especially in osteogenic differentiation. In this paper, we review related studies to provide new strategies for follow-up basic research and clinical applications.

Key words: N 6-methyladenosine, RNA modification, osteogenic differentiation, mesenchymal stem cell

中图分类号: 

  • Q254
[1] Bianco P, Robey PG, Simmons PJ . Mesenchymal stem cells: revisiting history, concepts, and assays[J]. Cell Stem Cell, 2008,2(4):313-319.
doi: 10.1016/j.stem.2008.03.002 pmid: 18397751
[2] Jing H, Liao L, An YL , et al. Suppression of EZH2 prevents the shift of osteoporotic MSC fate to adi-pocyte and enhances bone formation during osteo-porosis[J]. Mol Ther, 2016,24(2):217-229.
doi: 10.1038/mt.2015.152 pmid: 26307668
[3] Aghebati-Maleki L, Dolati S, Zandi R , et al. Prospect of mesenchymal stem cells in therapy of osteopo-rosis: a review[J]. J Cell Physiol, 2019,234(6):8570-8578.
doi: 10.1002/jcp.27833 pmid: 30488448
[4] Teven CM, Liu X, Hu N , et al. Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation[J]. Stem Cells Int, 2011,2011:201371.
doi: 10.4061/2011/201371 pmid: 21772852
[5] Cao YY, Yang HQ, Jin LY , et al. Genome-wide DNA methylation analysis during osteogenic differentia-tion of human bone marrow mesenchymal stem cells[J]. Stem Cell Int, 2018,2018:1-11.
[6] Wu YS, Zhou CC, Yuan Q . Role of DNA and RNA N6-adenine methylation in regulating stem cell fate[J]. Curr Stem Cell Res Ther, 2018,13(1):31-38.
doi: 10.2174/1574888X12666170621125457 pmid: 28637404
[7] Desrosiers R, Friderici K, Rottman F . Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells[J]. Proc Natl Acad Sci U S A, 1974,71(10):3971-3975.
doi: 10.1073/pnas.71.10.3971 pmid: 4372599
[8] Fu Y, Dominissini D, Rechavi G , et al. Gene expre-ssion regulation mediated through reversible m6A RNA methylation[J]. Nat Rev Genet, 2014,15(5):293-306.
doi: 10.1038/nrg3724 pmid: 24662220
[9] Shi HL, Wei JB, He C . Where, when, and how: context-dependent functions of RNA methylation writers, readers, and erasers[J]. Mol Cell, 2019,74(4):640-650.
doi: 10.1016/j.molcel.2019.04.025 pmid: 31100245
[10] Wang P, Doxtader KA, Nam Y . Structural basis for cooperative function of Mettl3 and Mettl14 methyl-transferases[J]. Mol Cell, 2016,63(2):306-317.
doi: 10.1016/j.molcel.2016.05.041 pmid: 27373337
[11] Zhou KI, Pan T . Structures of the m6A methyl-transferase complex: two subunits with distinct but coordinated roles[J]. Mol Cell, 2016,63(2):183-185.
doi: 10.1016/j.molcel.2016.07.005 pmid: 27447983
[12] Wang X, Feng J, Xue Y , et al. Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex[J]. Nature, 2016,534(7608):575-578.
doi: 10.1038/nature18298 pmid: 27281194
[13] Wang X, Huang JB, Zou TT , et al. Human m6A writers: two subunits, 2 roles[J]. RNA Biol, 2017,14(3):300-304.
doi: 10.1080/15476286.2017.1282025 pmid: 28121234
[14] Liu JZ, Yue YN, Han DL , et al. A METTL3-METTL- 14 complex mediates mammalian nuclear RNA N6-adenosine methylation[J]. Nat Chem Biol, 2014,10(2):93-95.
doi: 10.1038/nchembio.1432 pmid: 24316715
[15] Ping XL, Sun BF, Wang L , et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladeno-sine methyltransferase[J]. Cell Res, 2014,24(2):177-189.
doi: 10.1038/cr.2014.3 pmid: 24407421
[16] Gerken T, Girard CA, Tung YC , et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-de-pendent nucleic acid demethylase[J]. Science, 2007,318(5855):1469-1472.
doi: 10.1126/science.1151710 pmid: 17991826
[17] Gao X, Shin YH, Li M , et al. The fat mass and obe-sity associated gene FTO functions in the brain to regulate postnatal growth in mice[J]. PLoS One, 2010,5(11):e14005.
doi: 10.1371/journal.pone.0014005 pmid: 21103374
[18] Zhao X, Yang Y, Sun BF , et al. FTO-dependent de-methylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis[J]. Cell Res, 2014,24(12):1403-1419.
doi: 10.1038/cr.2014.151
[19] Zhang MZ, Zhang Y, Ma J , et al. The demethylase activity of FTO (fat mass and obesity associated protein) is required for preadipocyte differentiation[J]. PLoS One, 2015,10(7):e0133788.
doi: 10.1371/journal.pone.0133788 pmid: 26218273
[20] Zheng GQ, Dahl JA, Niu YM , et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility[J]. Mol Cell, 2013,49(1):18-29.
doi: 10.1016/j.molcel.2012.10.015 pmid: 23177736
[21] Du H, Zhao Y, He JQ , et al. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex[J]. Nat Com-mun, 2016,7:12626.
doi: 10.1038/ncomms12626 pmid: 27558897
[22] Berlivet S, Scutenaire J, Deragon JM , et al. Readers of the m6A epitranscriptomic code[J]. Biochim Biophys Acta Gene Regul Mech, 2019,1862(3):329-342.
doi: 10.1016/j.bbagrm.2018.12.008 pmid: 30660758
[23] Wang X, Lu ZK, Gomez A , et al. N6-methylade-nosine-dependent regulation of messenger RNA stability[J]. Nature, 2014,505(7481):117-120.
doi: 10.1038/nature12730 pmid: 24284625
[24] Xiao W, Adhikari S, Dahal U , et al. Nuclear m6A reader YTHDC1 regulates mRNA splicing[J]. Mol Cell, 2016,61(4):507-519.
doi: 10.1016/j.molcel.2016.01.012 pmid: 26876937
[25] Wang X, Zhao BS, Roundtree IA , et al. N6-me-thyladenosine modulates messenger RNA translation efficiency[J]. Cell, 2015,161(6):1388-1399.
doi: 10.1016/j.cell.2015.05.014 pmid: 26046440
[26] Schumann U, Shafik A, Preiss T . METTL3 gains R/W access to the epitranscriptome[J]. Mol Cell, 2016,62(3):323-324.
doi: 10.1016/j.molcel.2016.04.024 pmid: 27153530
[27] Ke SD, Alemu EA, Mertens C , et al. A majority of m6A residues are in the last exons, allowing the po-tential for 3’ UTR regulation[J]. Genes Dev, 2015,29(19):2037-2053.
doi: 10.1101/gad.269415.115 pmid: 26404942
[28] Meyer KD, Saletore Y, Zumbo P , et al. Compre-hensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons[J]. Cell, 2012,149(7):1635-1646.
doi: 10.1016/j.cell.2012.05.003 pmid: 22608085
[29] Meyer KD, Jaffrey SR . Rethinking m6A readers, writers, and erasers[J]. Annu Rev Cell Dev Biol, 2017,33:319-342.
doi: 10.1146/annurev-cellbio-100616-060758 pmid: 28759256
[30] Wu R, Li A, Sun BF , et al. A novel m6A reader Prrc2a controls oligodendroglial specification and myelina-tion [J]. Cell Res, 2019,29(1):23-41.
doi: 10.1038/s41422-018-0113-8 pmid: 30514900
[31] Ji PF, Wang X, Xie NN , et al. N6-methyladenosine in RNA and DNA: an epitranscriptomic and epige-netic player implicated in determination of stem cell fate[J]. Stem Cells Int, 2018,2018:3256524.
doi: 10.1155/2018/3256524 pmid: 30405719
[32] Cui Q, Shi HL, Ye P , et al. m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells[J]. Cell Rep, 2017,18(11):2622-2634.
doi: 10.1016/j.celrep.2017.02.059 pmid: 28297667
[33] Lee H, Bao SY, Qian YZ , et al. Stage-specific re-quirement for Mettl3-dependent m6A mRNA me-thylation during haematopoietic stem cell differen-tiation[J]. Nat Cell Biol, 2019,21(6):700-709.
doi: 10.1038/s41556-019-0318-1 pmid: 31061465
[34] Yang DD, Qiao J, Wang GY , et al. N6-Methyladeno-sine modification of lincRNA 1281 is critically re-quired for mESC differentiation potential[J]. Nucleic Acids Res, 2018,46(8):3906-3920.
doi: 10.1093/nar/gky130 pmid: 29529255
[35] Geula S, Moshitch-Moshkovitz S, Dominissini D , et al. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation[J]. Science, 2015,347(6225):1002-1006.
doi: 10.1126/science.1261417 pmid: 25569111
[36] Zhao BS, He C . Fate by RNA methylation: m6A steers stem cell pluripotency[J]. Genome Biol, 2015,16:43.
doi: 10.1186/s13059-015-0609-1 pmid: 25723450
[37] Zhang CX, Chen YS, Sun BF , et al. m6A modulates haematopoietic stem and progenitor cell specification[J]. Nature, 2017,549(7671):273-276.
doi: 10.1038/nature23883 pmid: 28869969
[38] Weng HY, Huang HL, Wu HZ , et al. METTL14 inhi-bits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m6A mo-dification[J]. Cell Stem Cell, 2018, 22(2): 191-205.e9.
doi: 10.1016/j.stem.2017.11.016 pmid: 29290617
[39] Yoon KJ, Ringeling FR, Vissers C , et al. Temporal control of mammalian cortical neurogenesis by m6A methylation[J]. Cell, 2017, 171(4): 877-889.e17.
doi: 10.1016/j.cell.2017.09.003 pmid: 28965759
[40] Li LP, Zang LQ, Zhang FR , et al. Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis[J]. Hum Mol Genet, 2017,26(13):2398-2411.
doi: 10.1093/hmg/ddx128 pmid: 28398475
[41] Wang Y, Li Y, Yue MH , et al. N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications[J]. Nat Neurosci, 2018,21(2):195-206.
doi: 10.1038/s41593-017-0057-1 pmid: 29335608
[42] Chen JC, Zhang YC, Huang CM , et al. m6A regulates neurogenesis and neuronal development by modula-ting histone methyltransferase Ezh2[J]. Genomics Proteomics Bioinformatics, 2019,17(2):154-168.
doi: 10.1016/j.gpb.2018.12.007 pmid: 31154015
[43] Wu YS, Xie L, Wang MY , et al. Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis[J]. Nat Commun, 2018,9(1):4772.
doi: 10.1038/s41467-018-06898-4 pmid: 30429466
[44] Tian C, Huang YL, Li QM , et al. Mettl3 regulates osteogenic differentiation and alternative splicing of vegfa in bone marrow mesenchymal stem cells[J]. Int J Mol Sci, 2019,20(3):E551.
doi: 10.3390/ijms20030551 pmid: 30696066
[45] Jüppner H, Abou-Samra AB, Freeman M , et al. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide[J]. Science, 1991,254(5034):1024-1026.
doi: 10.1126/science.1658941 pmid: 1658941
[46] Abou-Samra AB, Jüppner H, Force T , et al. Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor sti-mulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium[J]. Proc Natl Acad Sci U S A, 1992,89(7):2732-2736.
doi: 10.1073/pnas.89.7.2732 pmid: 1313566
[47] Balani DH, Ono N, Kronenberg HM . Parathyroid hormone regulates fates of murine osteoblast pre-cursors in vivo[J]. J Clin Invest, 2017,127(9):3327-3338.
doi: 10.1172/JCI91699 pmid: 28758904
[48] Rickard DJ, Wang FL, Rodriguez-Rojas AM , et al. Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte dif-ferentiation in human bone marrow stromal cells[J]. Bone, 2006,39(6):1361-1372.
doi: 10.1016/j.bone.2006.06.010 pmid: 16904389
[49] Shen WC, Lai YC, Li LH , et al. Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis[J]. Nat Commun, 2019,10(1):2226.
doi: 10.1038/s41467-019-10197-x pmid: 31110221
[50] Luo GM, Xu B, Huang YL . Icariside Ⅱ promotes the osteogenic differentiation of canine bone marrow mesenchymal stem cells via the PI3K/AKT/mTOR/S6K1 signaling pathways[J]. Am J Transl Res, 2017,9(5):2077-2087.
[51] Hui SY, Yang Y, Li J , et al. Differential miRNAs profile and bioinformatics analyses in bone marrow mesenchymal stem cells from adolescent idiopathic scoliosis patients[J]. Spine J, 2019,19(9):1584-1596.
doi: 10.1016/j.spinee.2019.05.003 pmid: 31100472
[52] Yao XD, Jing XZ, Guo JC , et al. Icariin protects bone marrow mesenchymal stem cells against iron overload induced dysfunction through mitochondrial fusion and fission, PI3K/AKT/mTOR and MAPK pathways[J]. Front Pharmacol, 2019,10:163.
doi: 10.3389/fphar.2019.00163 pmid: 30873034
[53] Lin H, Shabbir A, Molnar M , et al. Adenoviral ex-pression of vascular endothelial growth factor splice variants differentially regulate bone marrow-derived mesenchymal stem cells[J]. J Cell Physiol, 2008,216(2):458-468.
doi: 10.1002/jcp.21414 pmid: 18288639
[54] Li R, Nauth A, Li C , et al. Expression of VEGF gene isoforms in a rat segmental bone defect model treated with EPCs[J]. J Orthop Trauma, 2012,26(12):689-692.
doi: 10.1097/BOT.0b013e318266eb7e pmid: 22932749
[55] Carmeliet P, Ng YS, Nuyens D , et al. Impaired myo-cardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188[J]. Nat Med, 1999,5(5):495-502.
doi: 10.1038/8379 pmid: 10229225
[56] Shen GS, Zhou HB, Zhang H , et al. The GDF11-FTO-PPARγ axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis[J]. Biochim Biophys Acta Mol Basis Dis, 2018,1864(12):3644-3654.
doi: 10.1016/j.bbadis.2018.09.015 pmid: 30279140
[57] Liu WQ, Zhou LY, Zhou CC , et al. GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation[J]. Nat Commun, 2016,7:12794.
doi: 10.1038/ncomms12794 pmid: 27653144
[58] Takada I, Kouzmenko AP, Kato S . Wnt and PPARγ signaling in osteoblastogenesis and adipogenesis[J]. Nat Rev Rheumatol, 2009,5(8):442-447.
doi: 10.1038/nrrheum.2009.137 pmid: 19581903
[1] 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.
[2] 朱明静,张清彬. 生长因子诱导间充质干细胞三维体外软骨形成的研究进展[J]. 国际口腔医学杂志, 2020, 47(3): 270-277.
[3] 王润婷,房付春. 非编码RNA调控人牙周膜干细胞成骨向分化的研究进展[J]. 国际口腔医学杂志, 2020, 47(2): 138-145.
[4] 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.
[5] 冯顶丽,卓丽丹,芦笛,郭红延. 微小RNA调节间充质干细胞软骨分化机制的研究进展[J]. 国际口腔医学杂志, 2018, 45(6): 640-645.
[6] 葛逸弘, 房付春, 吴补领. 长链非编码RNA在间充质干细胞多向分化过程中的调节作用[J]. 国际口腔医学杂志, 2018, 45(3): 267-271.
[7] 武云舒, 袁泉. RNA腺嘌呤6-甲基化修饰调控干细胞分化的研究进展[J]. 国际口腔医学杂志, 2018, 45(3): 272-275.
[8] 刘珍珍, 方蛟, 赵静辉, 邹净亭, 相星辰, 王佳, 周延民. 牙龈干细胞生物学潜能的研究进展[J]. 国际口腔医学杂志, 2018, 45(1): 55-58.
[9] 薛令法, 张岱尊, 肖文林, 于保军. 机械牵张力促进小鼠骨髓间充质干细胞的成骨向分化[J]. 国际口腔医学杂志, 2017, 44(6): 679-685.
[10] 张建康, 卫俊俊, 唐曌隆, 余云波, 敬伟. Wnt和Notch通路在老龄个体骨髓间充质干细胞成骨中的调控[J]. 国际口腔医学杂志, 2017, 44(4): 459-465.
[11] 黄奕华 凌均棨. Toll样受体2和4在细胞成骨向分化中的作用[J]. 国际口腔医学杂志, 2015, 42(4): 492-495.
[12] 王涛1 廖天安1 王鸿1 邓伟1 于大海2. 血管内皮生长因子基因修饰骨髓间充质干细胞移植于放射治疗后组织的实验研究[J]. 国际口腔医学杂志, 2014, 41(2): 133-136.
[13] 张弘1综述 张志光2审校. 血管周细胞的研究进展[J]. 国际口腔医学杂志, 2013, 40(4): 529-532.
[14] 徐远明 樊明文 杨雪超. 间充质干细胞在肿瘤靶向治疗中的应用[J]. 国际口腔医学杂志, 2013, 40(3): 371-374.
[15] 苟文亭综述 叶玲 谭红审校. 牙髓干细胞分化的研究进展[J]. 国际口腔医学杂志, 2012, 39(3): 380-383.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 王昆润. 二甲亚砜和双氯芬酸并用治疗根尖周炎[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 潘劲松. 颈总动脉指压和颈内动脉球囊阻断试验在大脑血液动力学中的不同影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 王昆润. 后牙冠根斜形牙折的治疗[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨锦波. 嵌合体防龋疫苗的研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 丁刚. 应用硬组织代用品种植体行丰颏术[J]. 国际口腔医学杂志, 1999, 26(04): .
[6] 戴青. 口腔念珠菌病的新分类[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 蔡霞,李成章. 前列腺素E_2受体EP亚型在牙周炎发病机制中的作用[J]. 国际口腔医学杂志, 2005, 32(06): 461 -462 .
[8] 陈晓 蒋文晖 王文梅. 念珠菌性白斑的研究概况[J]. 国际口腔医学杂志, 2004, 31(02): 138 -140 .
[9] 轩东英,张建波 金岩. 胚胎发育期TGF-β超家族成员与腭裂发生的关系[J]. 国际口腔医学杂志, 2004, 31(02): 132 -134 .
[10] 黄维佳综述 平飞云审校. 涎腺黏膜相关淋巴组织淋巴瘤的研究进展[J]. 国际口腔医学杂志, 2009, 36(5): 577 -579 .