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中华口腔医学研究杂志(电子版) ›› 2020, Vol. 14 ›› Issue (05) : 271 -279. doi: 10.3877/cma.j.issn.1674-1366.2020.05.001

所属专题： 口腔医学； 文献；

中青年专家笔谈

长链非编码RNA调控成骨分化的研究现状及展望
李润泽1, 任剑寒1, 黄德兰1, 罗皓天1, 周晨1, 王伟财1,†()   
  1. 1. 中山大学附属口腔医院，光华口腔医学院，广东省口腔医学重点实验室，广州　510055
  • 收稿日期:2020-02-05 出版日期:2020-10-01
  • 通信作者: 王伟财

Research progress and prospects of long non-coding RNA regulating osteogenic differentiation

Runze Li1, Jianhan Ren1, Delan Huang1, Haotian Luo1, Chen Zhou1, Weicai Wang1,†()   

  1. 1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincal Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2020-02-05 Published:2020-10-01
  • Corresponding author: Weicai Wang
  • About author:
    Corresponding author: Wang Weicai, Email:
  • Supported by:
    National Key Research & Development (R & D) Plan Program(2016YFC20160905203); National Natural Science Foundation of China(81600824); Natural Science Foundation of Guangdong Province(2018A030310278); Science and Technology Program of Guangzhou(201707010106, 201804010459)
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引用本文：

李润泽, 任剑寒, 黄德兰, 罗皓天, 周晨, 王伟财. 长链非编码RNA调控成骨分化的研究现状及展望[J]. 中华口腔医学研究杂志(电子版), 2020, 14(05): 271-279.

Runze Li, Jianhan Ren, Delan Huang, Haotian Luo, Chen Zhou, Weicai Wang. Research progress and prospects of long non-coding RNA regulating osteogenic differentiation[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2020, 14(05): 271-279.

颅颌面骨缺损或异常不仅会造成相应功能的障碍，还会影响患者的美观及心理健康。间充质干细胞向成骨细胞谱系分化是骨组织发生与形成的物质基础，也是维持骨稳态的重要因素。成骨分化异常既与多种骨相关疾病有着密切关系，也会对骨组织修复产生消极影响。长链非编码RNA作为近年来新发现的调控因子，在成骨分化过程中发挥着重要的作用。本文拟阐述目前在成骨分化方面起重要调控作用的lncRNA及其机制，并探讨目前研究存在的不足及未来的发展前景。

关键词: 长链非编码RNA, 间充质干细胞, 成骨分化, 骨形成, 分子机制

Defect and abnormity of craniofacial bones not only cause corresponding functional disorders, but also affect the outlooking and mental health of patients. The osteogenic differentiation from mesenchymal stem cells to osteoblast lineage is not only the foundation of osteogenesis, but also one of the key factors maintaining bone homeostasis. Abnormal osteogenic differentiation is strongly relative to many bone diseases and has side effects on bone regeneration. As a newly discovered regulatory factor, long non-coding RNA plays an important role in osteogenic differentiation. This article focused on the long non-coding RNA that played important roles in regulating osteogenic differentiation, discussing the mechanisms, existing problems as well as prospects.

Key words: RNA, long noncoding, Mesenchymal stem cell, Osteogenic differentiation, Osteogenesis, Molecular mechanism
表1 与间充质干细胞成骨分化相关的长链非编码RNA
研究模型 LncRNA表达谱 注释 参考文献 年份
hBMSC 785个上调；623个下调 成骨诱导分化-未成骨诱导分化对比 [19] 2017
hBMSC 318个上调；732个下调 成骨诱导分化-未成骨诱导分化对比 [21] 2019
hBMSC 208个上调；131个下调 与hAMSC共培养后成骨诱导分化-未共培养后成骨诱导分化对比 [22] 2017
hBMSC 433个上调，233个下调 成骨诱导分化-未成骨诱导分化对比 [23] 2017
hBMSC 1392个上调，641个下调 经葡萄球菌A蛋白(SpA)处理后成骨诱导分化-未处理后成骨诱导分化对比 [24] 2016
hASC 478个上调；507下调 成骨诱导分化-未成骨诱导分化对比 [25] 2018
hASC 1460个上调，1112个下调 成骨诱导分化-未成骨诱导分化对比 [26] 2017
hPDLSC 777个上调；183个下调 成骨诱导分化-未成骨诱导分化对比 [27] 2017
mBMSC 16个上调；24个下调 成骨诱导分化-未成骨诱导分化对比 [28] 2018
mBMSC 140个上调；151个下调 成骨诱导分化-未成骨诱导分化对比 [29] 2018
rMSC 281个上调；14个下调 经4-胆甾烯-3-酮诱导成骨向分化-未经诱导对比 [30] 2018
iMSC 574个差异性表达 成骨诱导分化-未成骨诱导分化对比 [31] 2015
Mouse calvarial preosteoclast cells 3948个差异性表达 成骨诱导分化前期(2 ~ 8 d)与后期(10 ~ 18 d)对比 [32] 2018
C3H10T1/2 cells 59个上调；57个下调 骨形成蛋白2(BMP-2)处理前后对比 [33] 2013
图1 长链非编码RNA（lncRNA）调控成骨分化的相关机制LncRNA可在基因表达表观遗传水平、转录水平、转录后水平等发挥调控成骨分化的作用，参与骨多种生理及病理过程。A：LncRNA在基因表观遗传水平的调控：lncRNA ODIR1通过募集CUL3，介导FBXO25的降解，从而抑制FBXO25对OSX启动子区域H2BK120ub与H3K4me3修饰，进而抑制OSX的表达，最终抑制hUC-MSC成骨向的分化；B：LncRNA在基因转录水平的调控：lncRNA TUG1可在胞质结合p-SMAD5蛋白，抑制其核转位，从而显著抑制hBMSC的成骨分化；C：LncRNA调控pre-mRNA的选择性剪接：lncRNA RUNX2-AS1可通过特异性结合RUNX2 pre-mRNA的第七号内含子，从而阻止其后续的选择性剪接，进而抑制RUNX2的表达及hBMSC的成骨向分化；D：LncRNA调控miRNA的功能：lncRNA TCONS_00041960可通过ceRNA机制，富集miR-204-5p，解除其对Runx2的表达抑制，进而促进rBMSC成骨向分化
表2 长链非编码RNA（lncRNA）调控MSC成骨分化的研究总结
LncRNA 细胞模型 体内验证 调控机制 相关信号通路 作用效果 参考文献 年份
NKILA hMenSC & hUC-MSC 无 NF-κB/HDAC2/RUNX2;RXFP1/Akt NF-κB通路；PI3K-Akt通路 促成骨 [54] 2020
FER1L4 hPDLSC 有 miR-874-3p/VEGFA 未明确 促成骨 [55] 2020
LINC00707 hBMSC 无 miR-145/LRP5/β-catenin Wnt/β-catenin通路 促成骨 [56] 2020
HOXA-AS2 hUC-MSC 无 NF-κB/HDAC2/SP7 NF-κB通路 促成骨 [52] 2019
XIXT hBMSC 无 miR-30a-5p/RUNX2 未明确 促成骨 [57] 2019
MSC-AS1 BMSC 无 miR-140-5p/BMP2/Smad BMP通路 促成骨 [58] 2019
AK045490 MC3T3-E1 有 β-Catenin/TCF1/Runx2 Wnt/β-Catenin通路 抑制成骨 [40] 2019
LncRNA-OG hBMSC 有 hnRNPK/LncRNA-OG/BMP family BMP通路 促成骨 [21] 2019
HOXC-AS3 hBMSC;U266 cell line 有 提高HOXC10 mRNA稳定性 未明确 抑制成骨 [42] 2019
LOC103691336 rBMSC 有 miR-138-5p/BMP2 BMP通路 促成骨 [50] 2019
ODIR1 hUC-MSC 有 CUL3/FBXO25/OSX 未明确 抑制成骨 [35] 2019
HOTAIRM1 hMenSC;hUC-MSC 无 JNK/c-Jun/P300/RUNX2 JNK/AP-1通路 抑制成骨 [36] 2019
? hDFSC 无 DNMT1/HOXA2 未明确 促成骨 [37] 2020
SNHG1 mBMSC 无 Nedd4/p38 P38 MAPK通路 抑制成骨 [59] 2019
PCAT1 hASC 无 miR-145-5p/TLR4 TLR通路 促成骨 [20] 2018
HIF1A-AS2 hADSC 无 miR-665/IL6/PI3K/Akt PI3K/Akt通路 促成骨 [25] 2018
RUNX2-AS1 hBMSC 有 抑制RUNX2 pre-mRNA选择性剪接 未明确 抑制成骨 [41] 2018
DANCR hBMSC 无 抑制p38磷酸化 P38 MAPK通路 抑制成骨 [53] 2018
H19 mBMSC 无 miR-188/LCoR 不明 促成骨 [29] 2018
? hBMSC 无 miR-138/PTK2 PTK通路 促成骨 [60] 2018
KCNQ1OT1 mMSC 无 与Wnt/β-catenin通路相关 Wnt/β-catenin通路 促成骨 [46] 2018
Linc-ROR hBMSC 无 miR-138 & miR-145/ZEB2/β-catenin Wnt/β-catenin通路 促成骨 [43] 2018
MEG3 hBMSC 无 miR-133a-3p/SLC39A1 未明确 抑制成骨 [61] 2017
? hDFSC 无 EZH2/β-catenin Wnt/β-catenin通路 抑制成骨 [62] 2018
TUG1 hPDLSC 无 募集LIN28A 未明确 促成骨 [63] 2018
? hBMSC 无 抑制p-SMAD5核转位 未明确 抑制成骨 [39] 2019
TCONS_00041960 rBMSC 无 miR-204-5p/RUNX2 未明确 促成骨 [56] 2020
? hBMSC 无 miR-143/OSX 未明确 促成骨 [64] 2018
MALAT1 hASC 无 miR-30/RUNX2 未明确 促成骨 [65] 2019
? hBMSC & hFOB1.19 有 miR-34c/SATB2 未明确 促成骨 [66] 2019
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