title: Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes.
abstract: Osteoarthritis (OA) is a most common form of arthritis worldwide leading to significant disability. MicroRNAs (miRNAs) are non-coding RNAs involved in various aspects of cartilage development, homoeostasis and pathology. Several miRNAs have been identified which have shown to regulate expression of target genes relevant to OA pathogenesis such as matrix metalloproteinase (MMP)-13, cyclooxygenase (COX)-2, etc. Epigallocatechin-3-O-gallate (EGCG), the most abundant and active polyphenol in green tea, has been reported to have anti-arthritic effects, however, the role of EGCG in the regulation of miRNAs has not been investigated in OA. Here, we showed that EGCG inhibits COX-2 mRNA/protein expression or prostaglandin E2(PGE2) production via up-regulating microRNA hsa-miR-199a-3p expression in interleukin (IL)-1β-stimulated human OA chondrocytes. This negative co-regulation of hsa-miR-199a-3p and COX-2 by EGCG was confirmed by transfection of OA chondrocytes with anti-miR-199a-3p. Transfection of OA chondrocytes with anti-miR-199a-3p significantly enhanced COX-2 expression and PGE2production (P < 0.001), while EGCG treatment significantly inhibited anti-miR-199a-3p transfection-induced COX-2 expression or PGE2production in a dose-dependent manner. These results were further re-validated by co-treatment of these transfection OA chondrocytes with IL-1β and EGCG. EGCG treatment consistently up-regulated the IL-1β-decreased hsa-miR-199a-3p expression (P < 0.05) and significantly inhibited the IL-1β-induced COX-2 expression/PGE2production (P < 0.05) in OA chondrocytes transfected with anti-hsa-miR-199a-3p. Taken together, these results clearly indicate that EGCG inhibits COX-2 expression/PGE2production via up-regulation of hsa-miR-199a-3p expression. These novel pharmacological actions of EGCG on IL-1β-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds inhibit cartilage breakdown or pain by up-regulating the expression of microRNAs in human chondrocytes.
authors: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors: Zafar
authors: Z
authors: Rasheed
authors: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors: Naila
authors: N
authors: Rasheed
authors: Department of Dermatology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors: Hani A
authors: HA
authors: Al-Shobaili
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D002392:Catechin; C045651:epigallocatechin gallate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: 
  EGCG
  ; COX-2; chondrocytes; hsa-miR-199a-3p; osteoarthritis