Recruitment of Brd3 and Brd4 to acetylated chromatin is essential for proinflammatory cytokine-induced matrix-degrading enzyme expression

Journal of Orthopaedic Surgery and Research
Jin DaiQing Jiang

Abstract

Proinflammatory cytokines, which can upregulate the expression of matrix-degrading enzymes in chondrocytes, play important roles in the development of osteoarthritis. BET family proteins, acting as the "readers" of acetylated modifications on histones, have been linked to transcriptional regulation. And a BET protein inhibitor, I-BET151, has been shown to inhibit the induction of matrix-degrading enzymes by proinflammatory cytokines in chondrocytes. Our objective is to clarify the role and mechanism of BET proteins on matrix-degrading enzyme gene expression by using a human chondrosarcoma cell line (SW1353). We pretreated SW1353 cells with I-BET151 prior to treatment with IL-1β or TNF-α and then checked the expression of four matrix-degrading enzyme genes (MMP1, MMP3, MMP13, and ADAMTS4). We performed knockdown of BET protein family members (BRD2, BRD3, and BRD4) with corresponding siRNAs in SW1353 cells prior to treatment with IL-1β or TNF-α and checked the expression of the matrix-degrading enzyme genes. We evaluated Brd-mediated transcriptional regulation on the matrix-degrading enzyme genes by ChIP assay. We confirmed that I-BET151 could suppress the IL-1β- or TNF-α-induced expression of MMP1, MMP3, MMP13, and ADAMTS4 in SW...Continue Reading

References

Jul 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Anup DeyKeiko Ozato
Oct 19, 2004·Genes & Development·Robert J SimsDanny Reinberg
Mar 3, 2007·The Journal of Biological Chemistry·Shwu-Yuan Wu, Cheng-Ming Chiang
Apr 30, 2008·Methods : a Companion to Methods in Enzymology·Simon R TewTimothy E Hardingham
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Dec 2, 2010·Nature Reviews. Rheumatology·Mohit KapoorHassan Fahmi
Jun 23, 2012·Nature Reviews. Cancer·Anna C Belkina, Gerald V Denis
Oct 23, 2012·Nucleic Acids Research·Elisabeth ZieschéMichael Kracht
Jul 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Huajian TengRui Wang

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Citations

Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
May 4, 2021·Frontiers in Cell and Developmental Biology·Chao WanRocky S Tuan

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Methods Mentioned

BETA
acetylation
transfection
PCR
ChIP
electrophoresis
enhanced

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