ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway

被引:3
|
作者
Chen, Shuxiang [1 ]
Zhu, Xiaotong [2 ]
Ou, Wenhuan [1 ]
Kang, Le [1 ]
Situ, Jian [1 ]
Liao, Zhipeng [1 ]
Huang, Li [1 ]
Qi, Weizhong [3 ]
Ni, Songjia [3 ]
机构
[1] Jiangmen Wuyi Hosp Tradit Chinese Med, Dept Orthopaed, Jiangmen, Guangdong, Peoples R China
[2] Southern Med Univ, Zhujiang Hosp, Dept Rheumatol & Clin Immunol, Guangzhou, Peoples R China
[3] Southern Med Univ, Zhujiang Hosp, Dept Orthopaed, Guangzhou, Guangdong, Peoples R China
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS | 2023年 / 1866卷 / 04期
关键词
Osteoarthritis; ETS2; miR-155; DNMT1; STAT1; Cartilage injury; TRANSCRIPTION FACTOR; GENE-EXPRESSION; MUTANT P53; METHYLATION; CHONDROCYTES; PATHOGENESIS; SUPPRESSES; TARGET;
D O I
10.1016/j.bbagrm.2023.194965
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development of osteoarthritis (OA), but the potential functions and mechanism of most transcription factors in OA has not been completely illuminated. In this study, we identified that transcription factor V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) was significantly down-regulated in OA cartilage and IL-1 & beta;-induced OA chondrocytes. Functional experiments in vitro demonstrated that the overexpressed ETS2 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and ECM degradation in IL-1 & beta;-induced OA chondrocytes, whereas the knockdown of ETS2 led to the opposite effects. Further in vivo studies have shown that up-regulated ETS2 dramatically ameliorates cartilage injury in DMM-induced OA mice. Mechanical studies have disclosed that DNMT1-mediated downregulation of ETS2 dramatically promotes STAT1 by inhibiting miR-155 transcription, and increased STAT1 initiates a feedback loop that may enhance DNMT1-mediated hypermethylation of ETS2 to inhibit ETS2 expression, thus forming a DNMT1/ETS2/miR-155/STAT1 feedback loop that inhibits MAPK signaling pathways and aggravates OA cartilage injury. In all, our results revealed that overexpression of ETS2 markedly ameliorated OA cartilage injury through the ETS2/miR-155/STAT1/DNMT1 feedback loop, providing a new perspective on the pathogenesis and therapeutic strategies for OA.
引用
收藏
页数:19
相关论文
共 23 条
  • [1] The Role of Ets2 Transcription Factor in the Induction of MicroRNA-155 (miR-155) by Lipopolysaccharide and Its Targeting by Interleukin-10
    Quinn, Susan R.
    Mangan, Niamh E.
    Caffrey, Brian E.
    Gantier, Michael P.
    Williams, Bryan R. G.
    Hertzog, Paul J.
    McCoy, Claire E.
    O'Neill, Luke A. J.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (07) : 4316 - 4325
  • [2] Identification of the EBF1/ETS2/KLF2-miR-126-Gene Feed-Forward Loop in Breast Carcinogenesis and Stemness
    Gambacurta, Alessandra
    Tullio, Valentina
    Savini, Isabella
    Mauriello, Alessandro
    Catani, Maria Valeria
    Gasperi, Valeria
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2025, 26 (01)
  • [3] Transcriptional regulation of DUSP6 in a feedback loop manner responding to MAPK1 via ETS2 in human cells
    Furukawa, Toru
    Tanji, Etsuko
    Xu, Shanhai
    Horii, Akira
    CANCER RESEARCH, 2009, 69
  • [4] Feedback regulation of DUSP6 transcription responding to MAPK1 via ETS2 in human cells
    Furukawa, Toru
    Tanji, Etsuko
    Xu, Shanhai
    Horii, Akira
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 377 (01) : 317 - 320
  • [5] Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm
    Pahl, Matthew C.
    Erdman, Robert
    Kuivaniemi, Helena
    Lillvis, John H.
    Elmore, James R.
    Tromp, Gerard
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2015, 16 (05) : 11229 - 11258
  • [6] ETS2 promotes cardiomyocyte apoptosis and autophagy in heart failure by regulating lncRNA TUG1/miR-129-5p/ATG7 axis
    Tan, Li
    Xiong, Di
    Zhang, Hui
    Xiao, Sirou
    Yi, Ruilan
    Wu, Jian
    FASEB JOURNAL, 2023, 37 (06):
  • [7] RETRACTION: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Distress (Retraction of Vol 19, Pg 179, 2020)
    Jiang, Xiaohui
    Yu, Meihong
    Zhu, Taiping
    Lou, Lulu
    Chen, Xu
    Li, Qian
    Wei, Danhong
    Sun, Renhua
    MOLECULAR THERAPY-NUCLEIC ACIDS, 2022, 28 : 588 - 588
  • [8] ATG7 Overexpression Is Crucial for Tumorigenic Growth of Bladder Cancer In Vitro and In Vivo by Targeting the ETS2/miRNA196b/FOXO1/p27 Axis
    Zhu, Junlan
    Li, Yang
    Tian, Zhongxian
    Hua, Xiaohui
    Gu, Jiayan
    Li, Jingxia
    Liu, Claire
    Jin, Honglei
    Wang, Yulei
    Jiang, Guosong
    Huang, Haishan
    Huang, Chuanshu
    MOLECULAR THERAPY-NUCLEIC ACIDS, 2017, 7 : 299 - 313
  • [9] ETS1 Ameliorates Hyperoxia-Induced Alveolar Epithelial Cell Injury by Regulating the TGM2-Mediated Wnt/β-Catenin Pathway
    Yang, Min
    Gao, Xi-Rong
    Meng, Yan-Ni
    Shen, Fang
    Chen, Yan-Ping
    LUNG, 2021, 199 (06) : 681 - 690
  • [10] ETS1 Ameliorates Hyperoxia-Induced Alveolar Epithelial Cell Injury by Regulating the TGM2-Mediated Wnt/β-Catenin Pathway
    Min Yang
    Xi-Rong Gao
    Yan-Ni Meng
    Fang Shen
    Yan-Ping Chen
    Lung, 2021, 199 : 681 - 690