BET inhibitor JQ1 blocks inflammation and bone destruction

Journal of Dental Research

Volumn 93, Issue 7, 2014, Pages 657-662

  Meng, S ^a,b   Zhang, L ^a,b   Tang, Y ^a,b   Tu, Q ^a   Zheng, L ^a   Yu, L ^a   Murray, D ^a   Cheng, J ^a   Kim, S H ^c   Zhou, X ^b   Chen, J ^a,d  

^a TUFTS UNIVERSITY SCHOOL OF DENTAL MEDICINE   (United States)

^b SICHUAN UNIVERSITY   (China)

^c Kyung Hee University   (South Korea)

^d TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anti inflammatory agents; BRD4 protein; Epigenetics; Experimental animal models; Osteoclasts; Periodontitis

Indexed keywords

ACID PHOSPHATASE; ACID PHOSPHATASE TARTRATE RESISTANT ISOENZYME; ACP5 PROTEIN, MOUSE; BRD4 PROTEIN, MOUSE; CATHEPSIN K; CTSK PROTEIN, MOUSE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; ISOENZYME; LIPOPOLYSACCHARIDE; NFAB COMPLEX; NFATC1 PROTEIN, MOUSE; NUCLEAR PROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; PROTEIN C FOS; TLR2 PROTEIN, MOUSE; TLR4 PROTEIN, MOUSE; TNFSF11 PROTEIN, MOUSE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR ETS; TRANSCRIPTION FACTOR NFAT; TUMOR NECROSIS FACTOR;

ALVEOLAR BONE LOSS; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL DIFFERENTIATION; CELL LINE; DRUG EFFECTS; MOUSE; OSTEOCLAST; PERIODONTITIS; PROMOTER REGION;

ACID PHOSPHATASE; ALVEOLAR BONE LOSS; ANIMALS; CATHEPSIN K; CELL DIFFERENTIATION; CELL LINE; INTERLEUKIN-1BETA; ISOENZYMES; LIPOPOLYSACCHARIDES; MICE; NF-KAPPA B; NFATC TRANSCRIPTION FACTORS; NUCLEAR PROTEINS; OSTEOCLASTS; PERIODONTITIS; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS C-ETS; PROTO-ONCOGENE PROTEINS C-FOS; RANK LIGAND; TARTRATE-RESISTANT ACID PHOSPHATASE; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION FACTOR AP-1; TRANSCRIPTION FACTORS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84903954080     PISSN: 00220345     EISSN: 15440591     Source Type: Journal    
DOI: 10.1177/0022034514534261     Document Type: Article

References (28)

1. Amar S, Zhou Q, Shaik-Dasthagirisaheb Y, Leeman S (2007). Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge. Proc Natl Acad Sci USA 104:20466- 20471.
2. Bandukwala HS, Gagnon J, Togher S, Greenbaum JA, Lamperti ED, Parr NJ, et al. (2012). Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci USA 109:14532-14537.
3. Belkina AC, Nikolajczyk BS, Denis GV (2013). BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J Immunol 190:3670-3678.
4. Byun JS, Wong MM, Cui W, Idelman G, Li Q, De Siervi A, et al. (2009). Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes. Proc Natl Acad Sci USA 106:19286-19291.
5. Darveau RP (2010). Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol 8:481-490.
6. Dawson MA, Kouzarides T, Huntly BJ (2012). Targeting epigenetic readers in cancer. N Engl J Med 367:647-657.
7. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. (2011). BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146:904-917.
8. Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K (2003). The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc Natl Acad Sci USA 100:8758-8763. (Pubitemid 36899172)
9. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. (2010). Selective inhibition of BET bromodomains. Nature 468:1067- 1073.
10. Fowler T, Sen R, Roy AL (2011). Regulation of primary response genes. Mol Cell 44:348-360.
11. Hargreaves DC, Horng T, Medzhitov R (2009). Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138:129-145.
12. Huang B, Yang XD, Zhou MM, Ozato K, Chen LF (2009). Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 29:1375-1387.
13. Jung M, Philpott M, Muller S, Schulze J, Badock V, Eberspacher U, et al. (2014). Affinity map of BRD4 interactions with the histone H4 tail and the small molecule inhibitor JQ1. J Biol Chem 289:9304-9319.
14. LeRoy G, Rickards B, Flint SJ (2008). The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell 30:51-60. (Pubitemid 351470152)
15. Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, et al. (2012). Small-molecule inhibition of BRDT for male contraception. Cell 150:673-684.
16. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. (2011). Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA 108:16669-16674.
17. Muller S, Filippakopoulos P, Knapp S (2011). Bromodomains as therapeutic targets. Expert Rev Mol Med 13:e29.
18. Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, et al. (2010). Suppression of inflammation by a synthetic histone mimic. Nature 468:1119-1123.
19. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, et al. (2012). BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood 120:2843-2852.
20. Pasparakis M (2009). Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases. Nat Rev Immunol 9:778-788.
21. Prinjha RK, Witherington J, Lee K (2012). Place your BETs: the therapeutic potential of bromodomains. Trends Pharmacol Sci 33:146-153.
22. Tang X, Peng R, Phillips JE, Deguzman J, Ren Y, Apparsundaram S, et al. (2013). Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis. Am J Pathol 183:470-479.
23. Van Dyke TE (2007). Control of inflammation and periodontitis. Periodontol 2000 45:158-166.
24. Wienerroither S, Rauch I, Rosebrock F, Jamieson AM, Bradner J, Muhar M, et al. (2014). Regulation of NO synthesis, local inflammation, and innate immunity to pathogens by BET family proteins. Mol Cell Biol 34:415-427.
25. Wu SY, Chiang CM (2007). The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 282:13141- 13145.
26. Zhang G, Liu R, Zhong Y, Plotnikov AN, Zhang W, Zeng L, et al. (2012). Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. J Biol Chem 287:28840-28851.
27. Zhang W, Prakash C, Sum C, Gong Y, Li Y, Kwok JJ, et al. (2012). Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem 287:43137-43155.
28. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. (2011). RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478:524-528.