Please wait a minute...
浙江大学学报(医学版)  2019, Vol. 48 Issue (6): 682-687    DOI: 10.3785/j.issn.1008-9292.2019.12.14
综述     
组蛋白甲基化水平与骨关节炎病理发展的关联性
杜啸添1,2(),欧阳宏伟1,2,3,*()
1. 浙江大学医学院干细胞与再生医学系 浙江大学李达三·叶耀珍干细胞与再生医学研究中心, 浙江 杭州 310058
2. 浙江省组织工程与再生医学技术重点实验室, 浙江 杭州 310058
3. 浙江大学爱丁堡大学联合学院 浙江大学海宁国际校区, 浙江 海宁 314400
Correlation between histone methylation level and pathological development of osteoarthritis
DU Xiaotian1,2(),OUYANG Hongwei1,2,3,*()
1. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China
2. Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
3. Zhejiang University-University of Edinburgh Institute, International Campus of Zhejiang University, Haining 314400, Zhejiang Province, China
 全文: PDF(1056 KB)   HTML( 7 )
摘要:

骨关节炎是最常见的软骨退行性疾病。越来越多的研究显示,表观遗传学与骨关节炎之间密切相关,表观遗传修饰方式组蛋白甲基化水平与骨关节炎相关。组蛋白H3上不同氨基酸甲基化水平与骨关节炎病理发展的关联具体表现为第4位赖氨酸甲基化水平上升将加剧骨关节炎病理发展,而第9位与27位赖氨酸则呈现相反现象。因此,组蛋白甲基化修饰存在复杂网络,如能针对不同位置组蛋白的甲基化水平进行特异性靶向调控,有望延缓或阻止骨关节炎的发展。

关键词: 骨关节炎/病理学组蛋白类DNA甲基化综述    
Abstract:

Osteoarthritis is the most common degenerative cartilage disease. A large number of studies have shown the close association between epigenetics and osteoarthritis. Histone methylation is a type of epigenetic modification, and the link between histone methylation and osteoarthritis has also been revealed. In this article, we summarize the correlation between methylation levels of different histones and osteoarthritis in an attempt to explore the changes and regulation mechanisms of histone methylation in osteoarthritis. It has been shown that there are possible relations between the methylation levels of different amino acids on histone H3 and the pathological development of osteoarthritis; specifically, the rise of methylation level at the lysine 4 would aggravate the pathological development of osteoarthritis, while the the pattern of lysine 9 and 27 would be the opposite. These results indicate the possible existence of a complex network of histone methylation modifications. And the specific regulation of histone methylation levels in different positions may delay or prevent the occurrence and development of osteoarthritis.

Key words: Osteoarthritis/pathology    Histones    DNA methylation    Review
收稿日期: 2019-04-22 出版日期: 2020-01-19
:  R684.3  
基金资助: 国家自然科学基金(81630065)
通讯作者: 欧阳宏伟     E-mail: 21618580@zju.edu.cn;hwoy@zju.edu.cn
作者简介: 杜啸添(1991-), 男, 博士研究生, 主要从事骨关节炎表观遗传学修饰研究; E-mail:21618580@zju.edu.cn; https://orcid.org/0000-0002-7000-7828
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
杜啸添
欧阳宏伟

引用本文:

杜啸添,欧阳宏伟. 组蛋白甲基化水平与骨关节炎病理发展的关联性[J]. 浙江大学学报(医学版), 2019, 48(6): 682-687.

DU Xiaotian,OUYANG Hongwei. Correlation between histone methylation level and pathological development of osteoarthritis. J Zhejiang Univ (Med Sci), 2019, 48(6): 682-687.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.12.14        http://www.zjujournals.com/med/CN/Y2019/V48/I6/682

组蛋白位置 对骨关节炎的作用 参考文献
H3K4:组蛋白H3上的第4位赖氨酸;H3K9:组蛋白H3上的第9位赖氨酸;H3K27:组蛋白H3上的第27位赖氨酸;H3K79:组蛋白H3上的第79位赖氨酸.
H3K4 加剧 [10-12]
H3K9 缓解 [13-14]
H3K27 缓解 [15-18]
加剧 [6, 19-21]
H3K79 缓解 [22-24]
表 1  组蛋白甲基化水平上升加剧或缓解骨关节炎作用一览
1 WIELAND H A , MICHAELIS M , KIRSCHBAUM B J et al. Osteoarthritis-an untreatable disease?[J]. Nat Rev Drug Discov, 2005, 4 (4): 331- 344
doi: 10.1038/nrd1693
2 MOSKOWITZ R W . Osteoarthritis cartilage histopathology:grading and staging[J]. Osteoarthritis Cartilage, 2006, 14 (1): 1- 2
doi: 10.1016/j.joca.2005.08.015
3 MAHJOUB M , BERENBAUM F , HOUARD X . Why subchondral bone in osteoarthritis? The importance of the cartilage bone interface in osteoarthritis[J]. Osteoporos Int, 2012, 23 Suppl 8 S841- S846
4 EGGER G , LIANG G , APARICIO A et al. Epigenetics in human disease and prospects for epigenetic therapy[J]. Nature, 2004, 429 (6990): 457- 463
doi: 10.1038/nature02625
5 LUI J C , GARRISON P , NGUYEN Q et al. EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy[J]. Nat Commun, 2016, 7 13685
doi: 10.1038/ncomms13685
6 DAI J , YU D , WANG Y et al. Kdm6b regulates cartilage development and homeostasis through anabolic metabolism[J]. Ann Rheum Dis, 2017, 76 (7): 1295- 1303
doi: 10.1136/annrheumdis-2016-210407
7 BIRD A . Perceptions of epigenetics[J]. Nature, 2007, 447 (7143): 396- 398
doi: 10.1038/nature05913
8 BARSKI A , CUDDAPAH S , CUI K et al. High-resolution profiling of histone methylations in the human genome[J]. Cell, 2007, 129 (4): 823- 837
doi: 10.1016/j.cell.2007.05.009
9 HORIKE S , CAI S , MIYANO M et al. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome[J]. Nat Genet, 2005, 37 (1): 31- 40
doi: 10.1038/ng1491
10 SONG J , BAEK I J , CHUN C H et al. Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis[J]. Nat Commun, 2018, 9 (1): 3427
doi: 10.1038/s41467-018-05787-0
11 ZHANG M , LU Q , EGAN B et al. Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice[J]. Osteoarthritis Cartilage, 2016, 24 (7): 1274- 1283
doi: 10.1016/j.joca.2016.02.003
12 EL MANSOURI F E , CHABANE N , ZAYED N et al. Contribution of H3K4 methylation by SET-1A to interleukin-1-induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes[J]. Arthritis Rheum, 2011, 63 (1): 168- 179
doi: 10.1002/art.27762
13 EL MANSOURI F E , NEBBAKI S , KAPOOR M et al. THU0464 LSD1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1-induced microsomal prostaglandin e synthase-1 expression[J]. Ann Rheum Dis, 2014, 73 (2): 344
14 YANG L , LAWSON K A , TETEAK C J et al. ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates[J]. Dev Biol, 2013, 380 (1): 99- 110
doi: 10.1016/j.ydbio.2013.04.031
15 LIAN W S , KO J Y , WU R W et al. MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12[J]. Cell Death Dis, 2018, 9 (9): 919
doi: 10.1038/s41419-018-0994-y
16 YAPP C , CARR A J , PRICE A et al. H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis[J]. Arthritis Res Ther, 2016, 18 (1): 158
doi: 10.1186/s13075-016-1053-7
17 GAO B, LIN X, JING H, et al. Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti-inflammatory and angiogenic environment in aging mice[J/OL]. Aging Cell, 2018, 17(3): e12741.
18 CAKOUROS D , ISENMANN S , COOPER L et al. Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells[J]. Mol Cell Biol, 2012, 32 (8): 1433- 1441
doi: 10.1128/MCB.06315-11
19 CHEN L , WU Y , WU Y et al. The inhibition of EZH2 ameliorates osteoarthritis development through the Wnt/β-catenin pathway[J]. Sci Rep, 2016, 6 29176
doi: 10.1038/srep29176
20 AURY-LANDAS J , BAZILLE C , ALLAS L et al. Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes[J]. Sci Rep, 2017, 7 (1): 6483
21 WANG P, LI Y, MENG T, et al. KDM6A promotes chondrogenic differentiation of periodontal ligament stem cells by demethylation of SOX9[J/OL]. Cell Prolif, 2018, 51(3): e12413.
22 MONTEAGUDO S , CAILOTTO F , LORIES R J et al. A4.13? The DOT1L protein and gene network in chondrocytes identifies H3K79 histone methylation as key regulator of WNT and other growth factor cascades[J]. Ann Rheum Dis, 2015, 74 (1): A41
23 CASTA?O BETANCOURT M C , CAILOTTO F , KERKHOF H J et al. Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis[J]. Proc Natl Acad Sci U S A, 2012, 109 (21): 8218- 8223
doi: 10.1073/pnas.1119899109
24 MONTEAGUDO S , CORNELIS F , AZNAR-LOPEZ C et al. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis[J]. Nat Commun, 2017, 8 15889
doi: 10.1038/ncomms15889
25 WHETSTINE J R , NOTTKE A , LAN F et al. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases[J]. Cell, 2006, 125 (3): 467- 481
26 ZHANG M , LU Q , MILLER A H et al. Dynamic epigenetic mechanisms regulate age-dependent SOX9 expression in mouse articular cartilage[J]. Int J Biochem Cell Biol, 2016, 72 125- 134
doi: 10.1016/j.biocel.2016.01.013
27 SANTOS-ROSA H , SCHNEIDER R , BANNISTER A J et al. Active genes are tri-methylated at K4 of histone H3[J]. Nature, 2002, 419 (6905): 407- 411
doi: 10.1038/nature01080
28 WYSOCKA J , MYERS M P , LAHERTY C D et al. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1[J]. Genes Dev, 2003, 17 (7): 896- 911
doi: 10.1101/gad.252103
29 DOU Y , MILNE T A , RUTHENBURG A J et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components[J]. Nat Struct Mol Biol, 2006, 13 (8): 713- 719
doi: 10.1038/nsmb1128
30 WANG P , LIN C , SMITH E R et al. Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase Ⅱ[J]. Mol Cell Biol, 2009, 29 (22): 6074- 6085
doi: 10.1128/MCB.00924-09
31 ZHANG M , EGAN B , WANG J . Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes[J]. Int J Biochem Cell Biol, 2015, 67 101- 109
doi: 10.1016/j.biocel.2015.04.019
32 ROBERTS S B , WOOTTON E , DE FERRARI L et al. Epigenetics of osteoarticular diseases:recent developments[J]. Rheumatol Int, 2015, 35 (8): 1293- 1305
doi: 10.1007/s00296-015-3260-y
33 LAWSON K A , TETEAK C J , ZOU J et al. Mesenchyme-specific knockout of ESET histone methyltransferase causes ectopic hypertrophy and terminal differentiation of articular chondrocytes[J]. J Biol Chem, 2013, 288 (45): 32119- 32125
doi: 10.1074/jbc.M113.473827
34 KIM K I , PARK Y S , IM G I . Changes in the epigenetic status of the SOX-9 promoter in human osteoarthritic cartilage[J]. J Bone Miner Res, 2013, 28 (5): 1050- 1060
doi: 10.1002/jbmr.1843
35 RODOVA M , LU Q , LI Y et al. Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation[J]. J Bone Miner Res, 2011, 26 (8): 1974- 1986
doi: 10.1002/jbmr.397
36 PORTAL-Nú?EZ S , ESBRIT P , ALCARAZ M J et al. Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis[J]. Biochem Pharmacol, 2016, 108 1- 10
doi: 10.1016/j.bcp.2015.12.012
37 HONG S , CHO Y W , YU L R et al. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases[J]. Proc Natl Acad Sci U S A, 2007, 104 (47): 18439- 18444
doi: 10.1073/pnas.0707292104
38 XIANG Y , ZHU Z , HAN G et al. JMJD3 is a histone H3K27 demethylase[J]. Cell Res, 2007, 17 (10): 850- 857
doi: 10.1038/cr.2007.83
39 KONDO Y , SHEN L , CHENG A S et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation[J]. Nat Genet, 2008, 40 (6): 741- 750
doi: 10.1038/ng.159
40 SPAAPEN F, VAN DEN AKKER G G, CARON M M, et al. The immediate early gene product EGR1 and polycomb group proteins interact in epigenetic programming during chondrogenesis[J/OL]. PLoS One, 2013, 8(3): e58083.
41 LI J , OHLIGER J , PEI M . Significance of epigenetic landscape in cartilage regeneration from the cartilage development and pathology perspective[J]. Stem Cells Dev, 2014, 23 (11): 1178- 1194
doi: 10.1089/scd.2014.0002
42 ZHANG F , XU L , XU L et al. JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice[J]. J Mol Cell Biol, 2015, 7 (1): 23- 34
doi: 10.1093/jmcb/mjv003
43 GREENE M A , LOESER R F . Aging-related inflammation in osteoarthritis[J]. Osteoarthritis Cartilage, 2015, 23 (11): 1966- 1971
doi: 10.1016/j.joca.2015.01.008
44 MOBASHERI A , MATTA C , ZáKáNY R et al. Chondrosenescence:definition, hallmarks and potential role in the pathogenesis of osteoarthritis[J]. Maturitas, 2015, 80 (3): 237- 244
doi: 10.1016/j.maturitas.2014.12.003
45 MASTROGIACOMO M , CANCEDDA R , QUARTO R . Effect of different growth factors on the chondrogenic potential of human bone marrow stromal cells[J]. Osteoarthritis Cartilage, 2001, 9 Suppl A S36- S40
46 ZHANG R , MA J , HAN J et al. Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis[J]. Am J Transl Res, 2019, 11 (10): 6275- 6289
47 HE D , LIU J , HAI Y et al. Increased DOT1L in synovial biopsies of patients with OA and RA[J]. Clin Rheumatol, 2018, 37 (5): 1327- 1332
doi: 10.1007/s10067-017-3941-x
[1] 李雪,李文斌,封士兰,王荣. 血红蛋白在高原低氧适应中的机制研究进展[J]. 浙江大学学报(医学版), 2019, 48(6): 674-681.
[2] 丁怡丹,李文斌,王荣,张建春. 高原低氧对血脑屏障结构及其药物通透性影响的研究进展[J]. 浙江大学学报(医学版), 2019, 48(6): 668-673.
[3] 孔丽敏, 陆婧怡, 祝华建, 张建康. 选择性免疫蛋白酶体抑制剂研究进展[J]. 浙江大学学报(医学版), 2019, 48(6): 688-694.
[4] 姚旺祥,戴晗豪,桂鉴超. 机械应力促进炎性环境中软骨修复的机制研究[J]. 浙江大学学报(医学版), 2019, 48(5): 517-525.
[5] 徐佳俊,舒强. 三维打印技术在先天性心脏病中的应用[J]. 浙江大学学报(医学版), 2019, 48(5): 573-579.
[6] 张军浩,金静华,杨巍. 自噬调控血管平滑肌细胞功能在颅内动脉瘤形成和破裂中的作用[J]. 浙江大学学报(医学版), 2019, 48(5): 552-559.
[7] 陈钿雨,祁鸣. 单亲二体及其在癌症中的作用研究进展[J]. 浙江大学学报(医学版), 2019, 48(5): 560-566.
[8] 林静,陈志敏. 儿童重症腺病毒肺炎早期识别的研究进展[J]. 浙江大学学报(医学版), 2019, 48(5): 567-572.
[9] 黄淑敏,赵正言. 重症联合免疫缺陷病新生儿筛查及免疫系统重建研究进展[J]. 浙江大学学报(医学版), 2019, 48(4): 351-357.
[10] 陈光杰,王晓豪,唐达星. 性别发育异常的评估、诊断和治疗研究进展[J]. 浙江大学学报(医学版), 2019, 48(4): 358-366.
[11] 张建民. 缺血性脑血管疾病手术治疗新进展[J]. 浙江大学学报(医学版), 2019, 48(3): 233-240.
[12] 吴雨星, 张世红, 陈忠. 缰核及其神经环路在神经精神疾病中的作用研究进展[J]. 浙江大学学报(医学版), 2019, 48(3): 310-317.
[13] 张韵竹, 朱春鹏, 陆新良. 胃癌早期诊断的血清生物学标志物研究进展[J]. 浙江大学学报(医学版), 2019, 48(3): 326-333.
[14] 朱紫菱, 谈静, 邓红. 肿瘤细胞膜/质蛋白转位入核研究进展[J]. 浙江大学学报(医学版), 2019, 48(3): 318-325.
[15] BabooKalianee Devi,陈正云,张信美. 子宫腺肌病患者药物治疗进展[J]. 浙江大学学报(医学版), 2019, 48(2): 142-147.