Open AccessEpigallocatechin‐3‐ O ‐gallate up‐regulates microRNA‐199a‐3p expression by down‐regulating the expression of cyclooxygenase‐2 in stimulated human osteoarthritis chondrocytes
Author(s) -
Rasheed Zafar,
Rasheed Naila,
AlShobaili Hani A.
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12897
Subject(s) - transfection , microrna , osteoarthritis , cyclooxygenase , cartilage , prostaglandin e2 , chemistry , gene expression , gene silencing , matrix metalloproteinase , arthritis , regulation of gene expression , cancer research , microbiology and biotechnology , medicine , biology , gene , immunology , biochemistry , enzyme , pathology , anatomy , alternative medicine
Osteoarthritis ( OA ) is a most common form of arthritis worldwide leading to significant disability. Micro RNA s (mi RNA s) are non‐coding RNA s involved in various aspects of cartilage development, homoeostasis and pathology. Several mi RNA s 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 mi RNA s has not been investigated in OA . Here, we showed that EGCG inhibits COX ‐2 mRNA /protein expression or prostaglandin E 2 ( PGE 2 ) production via up‐regulating micro RNA 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 PGE 2 production ( P < 0.001), while EGCG treatment significantly inhibited anti‐miR‐199a‐3p transfection‐induced COX ‐2 expression or PGE 2 production 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/ PGE 2 production ( 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/ PGE 2 production 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 micro RNA s in human chondrocytes.