title: MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation.
abstract: Increased activity of histone deacetylase 2 (HDAC2) has been found in patients with osteoarthritis (OA) and cartilage matrix degradation and has been shown to mediate the repression of cartilage-specific gene expression in human chondrocytes. We aimed to determine whether microRNA-92a-3p (miR-92a-3p) regulates cartilage-specific gene expression via targeted HDAC2 in chondrogenesis and degradation.
  
  
  
  miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cells (hMSCs) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs), and in normal and OA human cartilage by in situ hybridization. hMSCs and PHCs were transfected with miR-92a-3p or its antisense inhibitor (anti-miR-92a-3p), respectively. PHCs were transfected with miR-92a-3p or anti-miR-92a-3p for 24 h before chromatin immunoprecipitation (ChIP) assay was performed with anti-ac-H3 antibody. Direct interaction between miR-92a-3p and its putative binding site in the 3'-untranslated region (3'-UTR) of HDAC2 mRNA was confirmed by luciferase reporter assay.
  
  
  
  miR-92a-3p expression was elevated in chondrogenic and hypertrophic hMSC, while reduced in OA cartilage compared with normal cartilage. The overexpression of miR-92a-3p suppressed the activity of a reporter construct containing the 3'-UTR and inhibited HDAC2 expression in both hMSCs and PHCs, while treatment with anti-miR-92a-3p enhanced HDAC2 expression. ChIP assays showed that miR-92a-3p enhances H3 acetylation on aggrecan (ACAN), cartilage oligomeric protein (COMP) and Col2a1 promoter, and also promotes relative cartilage matrix expression.
  
  
  
  Our results suggest that miR-92a-3p regulates cartilage development and homeostasis, which directly targets HDAC2, indicating histone hyperacetylation plays an important role in increased expression of cartilage matrix.
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: G
authors.initials: G
authors.lastname: Mao
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: F
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China. Electronic address: zhzhiqi@163.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China. Electronic address: neokang@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000107:Acetylation; D053674:Aggrecans / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D024043:Collagen Type II / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D042421:Histone Code; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D053674:Aggrecans; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D056464:Histone Deacetylase 2; D035683:MicroRNAs; D012333:RNA, Messenger; C499177:COL2A1 protein, human; C541874:MIRN92 microRNA, human; C533423:HDAC2 protein, human; C577553:TSP5 protein, human
keywords: Chondrocytes; Chondrogenesis; Histone deacetylase 2; MiRNA-92a-3p; Osteoarthritis