2. Academic Validation
  3. Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway

Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway

  • Biochem Biophys Res Commun. 2018 Sep 10;503(3):2061-2067. doi: 10.1016/j.bbrc.2018.07.160.
Lidi Deng 1,  Hong Hong 2,  Xueqin Zhang 1,  Dongru Chen 3,  Zhengyuan Chen 1,  Junqi Ling 4,  Liping Wu 5
Affiliations

Affiliations

  • 1 Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Guangdong, China.
  • 2 Zhujiang New Town Dental Clinic, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Guangdong, China.
  • 3 Department of Preventive Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Guangdong, China.
  • 4 Department of Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Guangdong, China. Electronic address: lingjq@mail.sysu.edu.cn.
  • 5 Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Guangdong, China. Electronic address: wulping@mail.sysu.edu.cn.
PMID: 30103943 DOI: 10.1016/j.bbrc.2018.07.160
Abstract

Our previous long noncoding RNA (lncRNA) microarray results showed that lncRNA MEG3 (maternally expressed 3) was significantly downregulated in human dental follicle cells than human periodontal ligament cells. Latest studies show that MEG3 contributes to polycomb repressive complex 2 (PRC2) recruitment to silence gene expression. The enhancer of zeste homolog 2 (EZH2), a crucial catalytic subunit of PRC2, mediates gene silencing and participates in cell lineage determination via methyltransferase activity. In this study, we found that the expression of EZH2 and H3K27me3 (trimethylation on lysine 27 in histone H3) decreased during osteogenesis of human dental follicle stem cells (hDFSCs). Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteogenesis of hDFSCs. We investigated the role of Wnt signaling pathway during the osteogenesis of hDFSCs and its relationship with EZH2. Besides, we studied the key genes of the canonical/noncanonical Wnt signaling pathway which might be related to EZH2. ChIP (chromatin immunoprecipitation) analysis showed that these effects were due to the EZH2 regulation of H3K27me3 level on the Wnt genes promotors. We first demonstrated that the decrease of MEG3 or EZH2 activated the Wnt/β-catenin signaling pathway via epigenetically regulating the H3K27me3 level on the Wnt genes promotors. Our research offers a new target for periodontal tissue engineering and osteogenic tissue regeneration.

Keywords

Epigenetics; Human dental follicle stem cells; LncRNA MEG3; Osteogenic differentiation; Wnt pathway.

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