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10.1186/ar4564 http://scihub22266oqcxt.onion/10.1186/ar4564 C4060543!4060543 !24886859     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24886859 &cmd=llinks): Failed to open stream: HTTP request failed! 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Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1?-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes |pdf=|usr=}}{{24886859 }} gab.com Text Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1 -induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes JO: Arthritis Res Ther http://www.kidney.de/pget.php?&tw=1&pmid=24886859 #FOAvip INTRODUCTION: Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE2, a critical mediator in the pathophysiology of osteoarthritis (OA). Histone methylation plays an important role in epigenetic gene regulation. In this study, we investigated the roles of histone H3 lysine 9 (H3K9) methylation in interleukin 1? (IL-1?)-induced mPGES-1 expression in human chondrocytes. METHODS: Chondrocytes were stimulated with IL-1?, and the expression of mPGES-1 mRNA was evaluated using real-time RT-PCR. H3K9 methylation and the recruitment of the histone demethylase lysine-specific demethylase 1 (LSD1) to the mPGES-1 promoter were evaluated using chromatin immunoprecipitation assays. The role of LSD1 was further evaluated using the pharmacological inhibitors tranylcypromine and pargyline and small interfering RNA (siRNA)-mediated gene silencing. The LSD1 level in cartilage was determined by RT-PCR and immunohistochemistry. RESULTS: The induction of mPGES-1 expression by IL-1? correlated with decreased levels of mono- and dimethylated H3K9 at the mPGES-1 promoter. These changes were concomitant with the recruitment of the histone demethylase LSD1. Treatment with tranylcypromine and pargyline, which are potent inhibitors of LSD1, prevented IL-1?-induced H3K9 demethylation at the mPGES-1 promoter and expression of mPGES-1. Consistently, LSD1 gene silencing with siRNA prevented IL-1?-induced H3K9 demethylation and mPGES-1 expression, suggesting that LSD1 mediates IL-1?-induced mPGES-1 expression via H3K9 demethylation. We show that the level of LSD1 was elevated in OA compared to normal cartilage. CONCLUSION: These results indicate that H3K9 demethylation by LSD1 contributes to IL-1?-induced mPGES-1 expression and suggest that this pathway could be a potential target for pharmacological intervention in the treatment of OA and possibly other arthritic conditions. Twit Text FOAVip Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1 -induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes ????Arthritis Res Ther http://www.kidney.de/pget.php?&tw=1&pmid=24886859 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24886859 #FOAvip English Wikipedia <ref>{{Cite pmid|24886859 }}</ref> Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1?-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes #MMPMID24886859 El Mansouri FE ; Nebbaki SS ; Kapoor M ; Afif H ; Martel-Pelletier J ; Pelletier JP ; Benderdour M ; Fahmi H Arthritis Res Ther 2014[May]; 16 (3 ): R113 PMID24886859 show ga INTRODUCTION: Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE2, a critical mediator in the pathophysiology of osteoarthritis (OA). Histone methylation plays an important role in epigenetic gene regulation. In this study, we investigated the roles of histone H3 lysine 9 (H3K9) methylation in interleukin 1? (IL-1?)-induced mPGES-1 expression in human chondrocytes. METHODS: Chondrocytes were stimulated with IL-1?, and the expression of mPGES-1 mRNA was evaluated using real-time RT-PCR. H3K9 methylation and the recruitment of the histone demethylase lysine-specific demethylase 1 (LSD1) to the mPGES-1 promoter were evaluated using chromatin immunoprecipitation assays. The role of LSD1 was further evaluated using the pharmacological inhibitors tranylcypromine and pargyline and small interfering RNA (siRNA)-mediated gene silencing. The LSD1 level in cartilage was determined by RT-PCR and immunohistochemistry. RESULTS: The induction of mPGES-1 expression by IL-1? correlated with decreased levels of mono- and dimethylated H3K9 at the mPGES-1 promoter. These changes were concomitant with the recruitment of the histone demethylase LSD1. Treatment with tranylcypromine and pargyline, which are potent inhibitors of LSD1, prevented IL-1?-induced H3K9 demethylation at the mPGES-1 promoter and expression of mPGES-1. Consistently, LSD1 gene silencing with siRNA prevented IL-1?-induced H3K9 demethylation and mPGES-1 expression, suggesting that LSD1 mediates IL-1?-induced mPGES-1 expression via H3K9 demethylation. We show that the level of LSD1 was elevated in OA compared to normal cartilage. CONCLUSION: These results indicate that H3K9 demethylation by LSD1 contributes to IL-1?-induced mPGES-1 expression and suggest that this pathway could be a potential target for pharmacological intervention in the treatment of OA and possibly other arthritic conditions. |Adult [MESH] |Aged [MESH] |Aged, 80 and over [MESH] |Blotting, Western [MESH] |Cells, Cultured [MESH] |Chondrocytes/*drug effects/metabolism [MESH] |Gene Expression/drug effects [MESH] |Histone Demethylases/antagonists & inhibitors/genetics/*metabolism [MESH] |Histones/*metabolism [MESH] |Humans [MESH] |Interleukin-1beta/*pharmacology [MESH] |Intramolecular Oxidoreductases/genetics/*metabolism [MESH] |Lysine/*metabolism [MESH] |Methylation/drug effects [MESH] |Middle Aged [MESH] |Monoamine Oxidase Inhibitors/pharmacology [MESH] |Osteoarthritis/genetics/metabolism/pathology [MESH] |Pargyline/pharmacology [MESH] |Promoter Regions, Genetic/genetics [MESH] |Prostaglandin-E Synthases [MESH] |Protein Binding [MESH] |RNA Interference [MESH] |Reverse Transcriptase Polymerase Chain Reaction [MESH]Lysine-specific demethylase 1-mediated demethylation of histone H3 lys(epmc).pdf DeepDyve Pubget Overpricing