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中华关节外科杂志(电子版) ›› 2021, Vol. 15 ›› Issue (06) : 693 -699. doi: 10.3877/cma.j.issn.1674-134X.2021.06.007

综述

长链非编码RNA H19影响骨关节炎中骨软骨代谢的研究进展
郑辉1, 罗雍猷2, 谢登辉1, 房健立1, 方航1, 张荣凯3,†()   
  1. 1. 510002　广州，南方医科大学第三附属医院关节外科
    2. 730000　兰州，解放军联勤保障部队第940医院
    3. 510002　广州，南方医科大学第三附属医院关节外科；860003　林芝市人民医院
  • 收稿日期:2020-12-01 出版日期:2021-12-01
  • 通信作者: 张荣凯
  • 基金资助:
    广州市科技计划项目(201904010034); 西藏自治区自然科学基金(XZ2020ZR-ZY65（Z）)

Research progress of long non-coding RNA H19 in osteoarthritis cartilage and subchondral boner

Hui Zheng1, Yongyou Luo2, Denghui Xie1, Jianli Fang1, Hang Fang1, Rongkai Zhang3,†()   

  1. 1. Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedic), Guangzhou 510002, China
    2. The 940th Hospital of Joint Logistics Support force of PLA, Lanzhou 730000, China
    3. Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedic), Guangzhou 510002, China; Linzhi People′s Hospital of Tibet, Linzhi 860003, China
  • Received:2020-12-01 Published:2021-12-01
  • Corresponding author: Rongkai Zhang
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引用本文：

郑辉, 罗雍猷, 谢登辉, 房健立, 方航, 张荣凯. 长链非编码RNA H19影响骨关节炎中骨软骨代谢的研究进展[J]. 中华关节外科杂志(电子版), 2021, 15(06): 693-699.

Hui Zheng, Yongyou Luo, Denghui Xie, Jianli Fang, Hang Fang, Rongkai Zhang. Research progress of long non-coding RNA H19 in osteoarthritis cartilage and subchondral boner[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2021, 15(06): 693-699.

长链非编码RNA(lncRNA)是一类长度约200 bp，一般不能进行蛋白质编码的长链RNA，有着多种多样的生物学功能。通过转录、翻译和DNA表观遗传修饰参与调控基因表达。作为一个相对新生的领域，目前对于lnc-RNA的研究主要集中在调控胚胎生长和干细胞分化以及肿瘤的发生和发展的监管作用。然而，越来越多的lncRNA被认为是与骨关节炎病理学相关的炎症途径的候选调节因子。此外，越来越多的研究发现lncRNA在骨关节炎关节组织中有差异表达。但lncRNA H19与骨关节炎(OA)相关性报道较少，在这篇综述中，以国内外最新研究为基础，重点介绍lncRNA H19在骨关节炎中的调控机制，包括翅缘缺刻(Notch)信号、无翼蛋白(Wnt)信号、内源竞争RNA(ceRNA)、lnc-RNA/微小RNA(microRNA)/信使RNA(mRNA)等。确定lncRNAs在骨关节炎中的表达和功能作用，不仅可以促进对骨关节炎病理学基础的表观遗传学的理解，而且最终可能有助于确定治疗干预的新靶点。

关键词: RNA,长链非编码, 骨关节炎

Long non-coding RNAs (lncRNAs) are a class of long non-coding RNAs about 200 bp in length that generally cannot be protein-encoded and have various biological functions. It is involved in the regulation of gene expression through transcriptional, translational and DNA epigenetic modifications. As a relatively nascent field, current research on lnc-RNA has focused on regulatory roles in the regulation of embryonic growth and stem cell differentiation as well as the development and progression of tumors. However, an increasing number of lncRNAs have been implicated as candidate regulators of inflammatory pathways associated with osteoarthritis pathology. In addition, more and more studies have found that lncRNAs are differentially expressed in osteoarthritic joint tissues. However, there are few reports on the correlation between lncRNAH19 and osteoarthritis (OA). Based on the latest research at home and abroad, this review focued on the regulatory mechanism of lncRNAH19 in osteoarthritis, including Notch signaling, wingless(Wnt)signaling, endogenous competitive RNAs (ceRNA), lnc-RNA/microRNA/messenger RNA(mRNA), etc. Determining the expression and functional roles of lncRNAs in osteoarthritis can not only advance the understanding of epigenetics underlying osteoarthritis pathology, but may ultimately help identify novel targets for therapeutic intervention.

Key words: RNA, long non-coding, Osteoarthritis
表1 lncRNA H19在癌症中的表达变化
癌症 lncRNA H19表达水平 机制
乳腺癌 上调 lncRNA H19/miR-675
肝癌 上调 H19 /miR-193a-3p/PSEN1
胃肠道癌 上调 H19作为ceRNA通过抑制let-7c调节HER2表达
胰腺癌 上调 H19/miR-675/E2F-1
胶质瘤 上调 lncRNA H19/ miR-29a/ vasohibin 2 (VASH2)
膀胱癌 上调 H19增加miR-675表达，抑制p53的活化，减少Bax/Bcl-2和cyclin D1的表达，进而导致膀胱癌
表2 不同lncRNA在OA关节组织中差异表达的证据
lncRNA种类 组织/细胞 表达水平 功能
H19 软骨细胞 上调 合成代谢功能[42]
CIR 软骨细胞 上调 促进MMP-13和ADAMTS5的表达[13]，同时抑制胶原和ACAN的生成
GAS5 软骨 下调 增加MMPs和ADAMTS4的表达，诱导凋亡[39]
FOXD2- AS1 软骨细胞 上调 促进软骨细胞的增殖[50]
HOTAIR 软骨细胞 上调 通过增强ADAMTS- 5 [51]在OA关节软骨细胞中其mRNA的稳定性来促进它的表达
ROR 软骨细胞 上调 调节细胞凋亡和软骨细胞自噬[52]
ZFAS1 软骨细胞 下调 促进软骨细胞增殖[53]
DANCR 软骨 上调 DANCR表达的抑制能够诱导OA细胞的凋亡[54]
BLACAT1 骨髓间充质干细胞 上调 抑制BMSCs增殖，Caspase 3活性增加，ALP活性降低
MIR4435-2HG 软骨细胞 下调 抑制软骨细胞凋亡[55]
TNFSF10 软骨细胞 上调 刺激软骨细胞的细胞增殖、抗凋亡和炎症[56]
ANCR 软骨细胞 上调 ANCR过表达促进软骨细胞的增殖，抑制TGF-β1表达[57]
图1 Lnc-RNA(长链非编码RNA) H19对成骨分化的调控机制示意图注：LEF-1(淋巴细胞增强因子-1)；TCF(T细胞因子)；FAK(粘着斑激酶)；PTK2(蛋白酪氨酸激酶2)；HDAC4/5(组蛋白脱乙酰酶4/5)；BMP9(骨形态发生蛋白9)
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