title: Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes.
  
  
  METHODS
  Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors.
  
  
  RESULTS
  Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the 'seed-matched-sequence' for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p.
  
  
  CONCLUSIONS
  This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.
authors.affiliation: Department of Medical Biochemistry, College of Medicine, Qassim University, P.O. Box 6655, Buraidah, 51452, Saudi Arabia. zafarrasheed@qumed.edu.sa.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Rasheed
authors.affiliation: Department of Medical Biochemistry, College of Medicine, Qassim University, P.O. Box 6655, Buraidah, 51452, Saudi Arabia.
authors.forename: Naila
authors.initials: N
authors.lastname: Rasheed
authors.affiliation: Department of Orthopedics, King Fahd Medical City, Riyadh, Saudi Arabia.
authors.forename: Osama
authors.initials: O
authors.lastname: Al-Shaya
mesh_terms: D020413:3' Untranslated Regions; D000071116:ADAMTS5 Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000627:therapeutic use; D001483:Base Sequence; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D017124:Conserved Sequence; D019587:Dietary Supplements; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020370:Osteoarthritis, Knee / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D000894:Anti-Inflammatory Agents, Non-Steroidal; C508585:IL1B protein, human; D053583:Interleukin-1beta; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D002392:Catechin; C045651:epigallocatechin gallate; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human
keywords: ADAMTS5; Chondrocytes; Hsa-miR-140-3p; MicroRNAs; Microarray; Osteoarthritis