PMID- 30854734 OWN - NLM STAT- MEDLINE DCOM- 20200814 LR - 20200814 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 120 IP - 8 DP - 2019 Aug TI - miR-193b-5p regulates chondrocytes metabolism by directly targeting histone deacetylase 7 in interleukin-1beta-induced osteoarthritis. PG - 12775-12784 LID - 10.1002/jcb.28545 [doi] AB - There is increasing evidence regarding the pivotal roles of microRNAs (miRNAs) and histone deacetylases (HDACs) in the development of osteoarthritis (OA). This study aimed to determine whether miR-193b-5p regulates HDAC7 expression directly to affect cartilage degeneration. Expression levels of miR-193b-5p, HDAC7, matrix metalloproteinase 3 (MMP3), and MMP13 were determined in normal and OA cartilage and primary human chondrocytes (PHCs) stimulated with interleukin-1beta (IL-1beta). PHCs were transfected with a miR-193b-5p mimic or inhibitor to verify whether miR-193b-5p influences the expression of HDAC7 and MMPs. A luciferase reporter assay was performed to demonstrate the binding between miR-193b-5p and the 3'-untranslated region (UTR) of HDAC7. Expression of miR-193b-5p was reduced in IL-1beta-stimulated PHCs and in OA cartilage compared to that in normal cartilage. Luciferase reporter assay exhibited the repressed activity of the reporter construct containing the 3'UTR of HDAC7. Both miR-193b-5p overexpression and HDAC7 inhibition decreased the expression of MMP3 and MMP13, whereas the inhibition of miR-193b-5p enhanced HDAC7, MMP3, and MMP13 expression. miR-193b-5p downregulates HDAC7 directly and, as a result, inhibits MMP3 and MMP13 expression, which suggests that miR-193b-5p has a protective role in OA. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Zhang, Chengyun AU - Zhang C AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Zhang, Zhiqi AU - Zhang Z AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Chang, Zongkun AU - Chang Z AUID- ORCID: 0000-0003-3970-3144 AD - Department of Orthopaedics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China. FAU - Mao, Guping AU - Mao G AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Hu, Shu AU - Hu S AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Zeng, Anyu AU - Zeng A AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Fu, Ming AU - Fu M AUID- ORCID: 0000-0002-5327-780X AD - Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190310 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (3' Untranslated Regions) RN - 0 (Interleukin-1beta) RN - 0 (MIRN193 microRNA, human) RN - 0 (MicroRNAs) RN - EC 3.4.24.- (MMP13 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.5.1.98 (HDAC7 protein, human) RN - EC 3.5.1.98 (Histone Deacetylases) SB - IM MH - 3' Untranslated Regions MH - Cells, Cultured MH - Chondrocytes/*cytology/drug effects/metabolism MH - Female MH - Histone Deacetylases/*genetics MH - Humans MH - Interleukin-1beta/*adverse effects MH - Male MH - Matrix Metalloproteinase 13/metabolism MH - Matrix Metalloproteinase 3/metabolism MH - MicroRNAs/*genetics MH - Middle Aged MH - Osteoarthritis/*genetics/metabolism MH - Primary Cell Culture OTO - NOTNLM OT - histone deacetylase 7 OT - matrix metalloproteinase 13 OT - matrix metalloproteinase 3 OT - miR-193b-5p OT - microRNAs OT - osteoarthritis EDAT- 2019/03/12 06:00 MHDA- 2020/08/15 06:00 CRDT- 2019/03/12 06:00 PHST- 2018/11/09 00:00 [received] PHST- 2018/12/14 00:00 [revised] PHST- 2019/01/10 00:00 [accepted] PHST- 2019/03/12 06:00 [pubmed] PHST- 2020/08/15 06:00 [medline] PHST- 2019/03/12 06:00 [entrez] AID - 10.1002/jcb.28545 [doi] PST - ppublish SO - J Cell Biochem. 2019 Aug;120(8):12775-12784. doi: 10.1002/jcb.28545. Epub 2019 Mar 10.