PMID- 36174738 OWN - NLM STAT- MEDLINE DCOM- 20221202 LR - 20230424 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 368 DP - 2022 Dec 1 TI - miR-200b-3p/ERG/PTHrP axis mediates the inhibitory effect of ethanol on the differentiation of fetal cartilage into articular cartilage. PG - 110201 LID - S0009-2797(22)00406-9 [pii] LID - 10.1016/j.cbi.2022.110201 [doi] AB - PURPOSE: This study aims to further explore cartilage development in prenatal ethanol exposure (PEE) offspring at different times to explore the specific time points and mechanism of ethanol-induced fetal cartilage dysplasia. METHODS: On gestational day (GD)14, GD17, and GD20, PEE fetal cartilage was evaluated by morphological analysis. RT-qPCR, immunohistochemistry, and immunofluorescence were used to detect the expression of cartilage marker genes and their regulatory factors. Bone marrow mesenchymal stem cells (BMSCs) were used to explore the effect of ethanol on the differentiation of chondrocytes. Additionally, we used inhibitors, overexpression plasmids and a luciferase reporter assay on GD17 chondrocytes to verify the mechanism. RESULTS: PEE significantly reduced cartilage matrix content and the expression of marker genes on GD17 and GD20 but had no effect on GD14. The inhibition of chondrogenic differentiation by PEE mainly occurred on GD14-17. Furthermore, the expression of miR-200b-3p was increased, while that of ERG and PTHrP was markedly reduced in PEE fetal cartilage. In vitro, ethanol (30-120 mM) inhibited the differentiation of BMSCs into chondrocytes in a concentration-dependent manner, accompanied by strong expression of miR-200b-3p and low expression of ERG and PTHrP. Moreover, PTHLH and ERG overexpressed, as well as a miR-200b-3p inhibitor reversed the inhibitory effect of ethanol on the differentiation of fetal chondrocytes. Furthermore, miR-200b-3p could target and negatively regulate ERG. CONCLUSIONS: PEE can significantly inhibit the development of articular cartilage, especially during articular cartilage formation. The mechanism is related to the decreased differentiation of fetal cartilage into articular cartilage mediated by the miR-200b-3p/ERG/PTHrP axis. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Ni, Qubo AU - Ni Q AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: niqubo@163.com. FAU - Chen, Haitao AU - Chen H AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: chenht33@sina.com. FAU - Li, Bin AU - Li B AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: libin19901206@163.com. FAU - He, Hangyuan AU - He H AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: 1573185673@qq.com. FAU - Shi, Huasong AU - Shi H AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: 976308498@qq.com. FAU - Zhu, Jiayong AU - Zhu J AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: jarry.zhu@qq.com. FAU - Wang, Hui AU - Wang H AD - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan, 430071, China. Electronic address: wanghui19@whu.edu.cn. FAU - Chen, Liaobin AU - Chen L AD - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan, 430071, China. Electronic address: lbchen@whu.edu.cn. LA - eng PT - Journal Article DEP - 20220926 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 3K9958V90M (Ethanol) RN - 0 (MicroRNAs) RN - 0 (Parathyroid Hormone-Related Protein) RN - 0 (Transcriptional Regulator ERG) SB - IM EIN - Chem Biol Interact. 2023 Jun 1;378:110481. PMID: 37094432 MH - Female MH - Pregnancy MH - *Cartilage, Articular/metabolism MH - Chondrocytes MH - Ethanol/pharmacology/metabolism MH - *MicroRNAs/metabolism MH - Parathyroid Hormone-Related Protein/genetics/metabolism/pharmacology MH - Transcriptional Regulator ERG/metabolism OTO - NOTNLM OT - Articular cartilage OT - ERG OT - PTHrP OT - Prenatal ethanol exposure OT - miR-200b-3p COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/09/30 06:00 MHDA- 2022/11/29 06:00 CRDT- 2022/09/29 19:33 PHST- 2022/08/18 00:00 [received] PHST- 2022/09/09 00:00 [revised] PHST- 2022/09/21 00:00 [accepted] PHST- 2022/09/30 06:00 [pubmed] PHST- 2022/11/29 06:00 [medline] PHST- 2022/09/29 19:33 [entrez] AID - S0009-2797(22)00406-9 [pii] AID - 10.1016/j.cbi.2022.110201 [doi] PST - ppublish SO - Chem Biol Interact. 2022 Dec 1;368:110201. doi: 10.1016/j.cbi.2022.110201. Epub 2022 Sep 26.