PMID- 31202458 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20200713 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 516 IP - 1 DP - 2019 Aug 13 TI - DLX3 regulates osteogenic differentiation of bone marrow mesenchymal stem cells via Wnt/beta-catenin pathway mediated histone methylation of DKK4. PG - 171-176 LID - S0006-291X(19)31152-0 [pii] LID - 10.1016/j.bbrc.2019.06.029 [doi] AB - OBJECTIVE: Distal-less homeobox 3 (DLX3) is an important transcription factor involved in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism is not clear. This study investigated the underlying mechanism of DLX3 in osteogenic differentiation. METHODS: DLX3 overexpression and knockdown in cells were achieved using lentiviruses. The osteogenic differentiation of BMSCs was detected using alkaline phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and chromatin immunoprecipitation (ChIP) assays. RESULTS: DLX3 overexpression promoted the osteogenic differentiation of BMSCs, whereas DLX3 knockdown reduced the osteogenic differentiation of BMSCs. RT-qPCR and Western blotting assays showed that DLX3 modulated osteogenic differentiation via the Wnt/beta-catenin pathway. ChIP-qPCR showed that DLX3 knockdown promoted DKK4 expression by decreasing the enrichment of histone H3 lysine 27 trimethylation (H3K27me3) in the promotor region of DKK4. CONCLUSION: Our data implied that DLX3 regulated Wnt/beta-catenin pathway through histone modification of DKK4 during the osteogenic differentiation of BMSCs. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Sun, Shichen AU - Sun S AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. FAU - Yu, Miao AU - Yu M AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. FAU - Fan, Zhuangzhuang AU - Fan Z AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. FAU - Yeh, I-Ting AU - Yeh IT AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. FAU - Feng, Hailan AU - Feng H AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. FAU - Liu, Haochen AU - Liu H AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. Electronic address: talentlhc@163.com. FAU - Han, Dong AU - Han D AD - Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. Electronic address: donghan@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190613 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (DKK4 protein, human) RN - 0 (Distal-less homeobox proteins) RN - 0 (Histones) RN - 0 (Homeodomain Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Transcription Factors) SB - IM MH - Cell Differentiation MH - Cells, Cultured MH - Histones/*metabolism MH - Homeodomain Proteins/*metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins/*metabolism MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Methylation MH - *Osteogenesis MH - Transcription Factors/*metabolism MH - *Wnt Signaling Pathway OTO - NOTNLM OT - DKK4 OT - DLX3 OT - Epigenetic regulation OT - Histone methylation OT - Osteogenic differentiation EDAT- 2019/06/17 06:00 MHDA- 2020/07/14 06:00 CRDT- 2019/06/17 06:00 PHST- 2019/06/01 00:00 [received] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/17 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2019/06/17 06:00 [entrez] AID - S0006-291X(19)31152-0 [pii] AID - 10.1016/j.bbrc.2019.06.029 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2019 Aug 13;516(1):171-176. doi: 10.1016/j.bbrc.2019.06.029. Epub 2019 Jun 13.