Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation.
15-LOX-1
Cartilage
DNA methylation
Epigenetics
Osteoarthritis chondrocyte
Journal
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
Titre abrégé: Inflamm Res
Pays: Switzerland
ID NLM: 9508160
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
05
08
2023
accepted:
10
10
2023
revised:
23
09
2023
medline:
20
11
2023
pubmed:
24
10
2023
entrez:
24
10
2023
Statut:
ppublish
Résumé
15-Lipoxygenase-1 (15-LOX-1) catalyzes the biosynthesis of many anti-inflammatory and immunomodulatory lipid mediators and was reported to have protective properties in several inflammatory conditions, including osteoarthritis (OA). This study was designed to evaluate the expression of 15-LOX-1 in cartilage from normal donors and patients with OA, and to determine whether it is regulated by DNA methylation. Cartilage samples were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee joint replacement surgery. The expression of 15-LOX-1 was evaluated using real-time polymerase chain reaction (PCR). The role of DNA methylation in 15-LOX-1 expression was assessed using the DNA methyltransferase inhibitor 5-Aza-2'-desoxycytidine (5-Aza-dC). The effect of CpG methylation on 15-LOX-1 promoter activity was evaluated using a CpG-free luciferase vector. The DNA methylation status of the 15-LOX-1 promoter was determined by pyrosequencing. Expression of 15-LOX-1 was upregulated in OA compared to normal cartilage. Treatment with 5-Aza-dC increased 15-LOX-1 mRNA levels in chondrocytes, and in vitro methylation decreased 15-LOX-1 promoter activity. There was no difference in the methylation status of the 15-LOX-1 gene promoter between normal and OA cartilage. The expression level of 15-LOX-1 was elevated in OA cartilage, which may be part of a repair process. The upregulation of 15-LOX-1 in OA cartilage was not associated with the methylation status of its promoter, suggesting that other mechanisms are involved in its upregulation.
Identifiants
pubmed: 37874359
doi: 10.1007/s00011-023-01805-0
pii: 10.1007/s00011-023-01805-0
doi:
Substances chimiques
Arachidonate 15-Lipoxygenase
EC 1.13.11.33
Scavenger Receptors, Class E
0
ALOX15 protein, human
EC 1.13.11.33
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2145-2153Subventions
Organisme : CIHR
ID : PJT-1751110
Pays : Canada
Organisme : CIHR
ID : PJT-180297
Pays : Canada
Organisme : CIHR
ID : PJT-1751110
Pays : Canada
Organisme : CIHR
ID : PJT-180297
Pays : Canada
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Hugle T, Geurts J. What drives osteoarthritis?-synovial versus subchondral bone pathology. Rheumatology (Oxford). 2017;56:1461–71.
pubmed: 28003493
Wei Y, Bai L. Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis. Connect Tissue Res. 2016;57:245–61.
pubmed: 27285430
Vecellio M, Wu H, Lu Q, Selmi C. The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases. Clin Rheumatol. 2021;40:459–76.
pubmed: 32613397
Funes SC, Fernandez-Fierro A, Rebolledo-Zelada D, Mackern-Oberti JP, Kalergis AM. Contribution of dysregulated DNA methylation to autoimmunity. Int J Mol Sci. 2021;22:11892.
pubmed: 34769338
pmcid: 8584328
Edwards JR, Yarychkivska O, Boulard M, Bestor TH. DNA methylation and DNA methyltransferases. Epigenetics Chromatin. 2017;10:23.
pubmed: 28503201
pmcid: 5422929
Lyko F. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet. 2018;19:81–92.
pubmed: 29033456
Hashimoto K, Otero M, Imagawa K, de Andres MC, Coico JM, Roach HI, et al. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1beta (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites. J Biol Chem. 2013;288:10061–72.
pubmed: 23417678
pmcid: 3617244
Yang F, Zhou S, Wang C, Huang Y, Li H, Wang Y, et al. Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients. Sci Rep. 2017;7:43592.
pubmed: 28262826
pmcid: 5337936
Takahashi A, de Andres MC, Hashimoto K, Itoi E, Oreffo RO. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthritis Cartilage. 2015;23:1946–54.
pubmed: 26521741
pmcid: 4638192
de Andres MC, Takahashi A, Oreffo RO. Demethylation of an NF-kappaB enhancer element orchestrates iNOS induction in osteoarthritis and is associated with altered chondrocyte cell cycle. Osteoarthritis Cartilage. 2016;24:1951–60.
pubmed: 27307355
Cheung KS, Hashimoto K, Yamada N, Roach HI. Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatol Int. 2009;29:525–34.
pubmed: 18941754
Shen J, Wang C, Li D, Xu T, Myers J, Ashton JM, et al. DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism. JCI Insight. 2017;2:e93612.
pubmed: 28614801
pmcid: 5470890
Ivanov I, Kuhn H, Heydeck D. Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15). Gene. 2015;573:1–32.
pubmed: 26216303
pmcid: 6728142
Tian R, Zuo X, Jaoude J, Mao F, Colby J, Shureiqi I. ALOX15 as a suppressor of inflammation and cancer: lost in the link. Prostaglandins Other Lipid Mediat. 2017;132:77–83.
pubmed: 28089732
pmcid: 5509529
Mashima R, Okuyama T. The role of lipoxygenases in pathophysiology; new insights and future perspectives. Redox Biol. 2015;6:297–310.
pubmed: 26298204
pmcid: 4556770
Tang DG, Bhatia B, Tang S, Schneider-Broussard R. 15-lipoxygenase 2 (15-LOX2) is a functional tumor suppressor that regulates human prostate epithelial cell differentiation, senescence, and growth (size). Prostaglandins Other Lipid Mediat. 2007;82:135–46.
pubmed: 17164141
Suraneni MV, Moore JR, Zhang D, Badeaux M, Macaluso MD, DiGiovanni J, et al. Tumor-suppressive functions of 15-lipoxygenase-2 and RB1CC1 in prostate cancer. Cell Cycle. 2014;13:1798–810.
pubmed: 24732589
pmcid: 4111726
Chabane N, Zayed N, Benderdour M, Martel-Pelletier J, Pelletier JP, Duval N, et al. Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis. Arthritis Res Ther. 2009;11:R44.
pubmed: 19296842
pmcid: 2688191
Benabdoune H, Rondon EP, Shi Q, Fernandes J, Ranger P, Fahmi H, et al. The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis. Inflamm Res. 2016;65:635–45.
pubmed: 27056390
Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S. Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol. 2000;164:2660–6.
pubmed: 10679106
Kure I, Nishiumi S, Nishitani Y, Tanoue T, Ishida T, Mizuno M, et al. Lipoxin A(4) reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-kappaB activation. J Pharmacol Exp Ther. 2010;332:541–8.
pubmed: 19846590
Habouri L, El Mansouri FE, Ouhaddi Y, Lussier B, Pelletier JP, Martel-Pelletier J, et al. Deletion of 12/15-lipoxygenase accelerates the development of aging-associated and instability-induced osteoarthritis. Osteoarthritis Cartilage. 2017;25:1719–28.
pubmed: 28694081
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.
pubmed: 11846609
El Mansouri FE, Nebbaki SS, Kapoor M, Afif H, Martel-Pelletier J, Pelletier JP, et al. Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes. Arthritis Res Ther. 2014;16:R113.
pubmed: 24886859
pmcid: 4060543
Gebhard C, Benner C, Ehrich M, Schwarzfischer L, Schilling E, Klug M, et al. General transcription factor binding at CpG islands in normal cells correlates with resistance to de novo DNA methylation in cancer cells. Cancer Res. 2010;70:1398–407.
pubmed: 20145141
Dakin SG, Colas RA, Newton J, Gwilym S, Jones N, Reid HAB, et al. 15-Epi-LXA4 and MaR1 counter inflammation in stromal cells from patients with Achilles tendinopathy and rupture. FASEB J. 2019;33:8043–54.
pubmed: 30916999
pmcid: 6593888
Namgaladze D, Snodgrass RG, Angioni C, Grossmann N, Dehne N, Geisslinger G, et al. AMP-activated protein kinase suppresses arachidonate 15-lipoxygenase expression in interleukin 4-polarized human macrophages. J Biol Chem. 2015;290:24484–94.
pubmed: 26276392
pmcid: 4591829
Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, et al. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol. 2006;176:1848–59.
pubmed: 16424216
Rohwer N, Chiu CY, Huang D, Smyl C, Rothe M, Rund KM, et al. Omega-3 fatty acids protect from colitis via an Alox15-derived eicosanoid. FASEB J. 2021;35: e21491.
pubmed: 33710695
Conte FP, Menezes-de-Lima O Jr, Verri WA Jr, Cunha FQ, Penido C, Henriques MG. Lipoxin A(4) attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects. Br J Pharmacol. 2010;161:911–24.
pubmed: 20860668
pmcid: 2992904
Dean S, Wang CS, Nam K, Maruyama CL, Trump BG, Baker OJ. Aspirin triggered resolvin D1 reduces inflammation and restores saliva secretion in a Sjogren’s syndrome mouse model. Rheumatology (Oxford). 2019;58:1285–92.
pubmed: 30877775
Serhan CN, Jain A, Marleau S, Clish C, Kantarci A, Behbehani B, et al. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol. 2003;171:6856–65.
pubmed: 14662892
Shen J, Herderick E, Cornhill JF, Zsigmond E, Kim HS, Kuhn H, et al. Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J Clin Invest. 1996;98:2201–8.
pubmed: 8941635
pmcid: 507668
Kronke G, Katzenbeisser J, Uderhardt S, Zaiss MM, Scholtysek C, Schabbauer G, et al. 12/15-lipoxygenase counteracts inflammation and tissue damage in arthritis. J Immunol. 2009;183:3383–9.
pubmed: 19675173
Gronert K, Maheshwari N, Khan N, Hassan IR, Dunn M, Laniado SM. A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J Biol Chem. 2005;280:15267–78.
pubmed: 15708862
Kronke G, Reich N, Scholtysek C, Akhmetshina A, Uderhardt S, Zerr P, et al. The 12/15-lipoxygenase pathway counteracts fibroblast activation and experimental fibrosis. Ann Rheum Dis. 2012;71:1081–7.
pubmed: 22267335
Rice SJ, Beier F, Young DA, Loughlin J. Interplay between genetics and epigenetics in osteoarthritis. Nat Rev Rheumatol. 2020;16:268–81.
pubmed: 32273577
Aubourg G, Rice SJ, Bruce-Wootton P, Loughlin J. Genetics of osteoarthritis. Osteoarthritis Cartilage. 2022;30:636–49.
pubmed: 33722698
pmcid: 9067452
Sesselmann S, Soder S, Voigt R, Haag J, Grogan SP, Aigner T. DNA methylation is not responsible for p21WAF1/CIP1 down-regulation in osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2009;17:507–12.
pubmed: 18954998
Poschl E, Fidler A, Schmidt B, Kallipolitou A, Schmid E, Aigner T. DNA methylation is not likely to be responsible for aggrecan down regulation in aged or osteoarthritic cartilage. Ann Rheum Dis. 2005;64:477–80.
pubmed: 15708898
pmcid: 1755386
Aref-Eshghi E, Liu M, Razavi-Lopez SB, Hirasawa K, Harper PE, Martin G, et al. SMAD3 is upregulated in human osteoarthritic cartilage independent of the promoter DNA methylation. J Rheumatol. 2016;43:388–94.
pubmed: 26669923
de Andres MC, Imagawa K, Hashimoto K, Gonzalez A, Goldring MB, Roach HI, et al. Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis. Biochem Biophys Res Commun. 2011;407:54–9.
pubmed: 21352802
pmcid: 3937865
Liu C, Schain F, Han H, Xu D, Andersson-Sand H, Forsell P, et al. Epigenetic and transcriptional control of the 15-lipoxygenase-1 gene in a Hodgkin lymphoma cell line. Exp Cell Res. 2012;318:169–76.
pubmed: 22094113
Kelavkar UP, Harya NS, Hutzley J, Bacich DJ, Monzon FA, Chandran U, et al. DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation. Prostaglandins Other Lipid Mediat. 2007;82:185–97.
pubmed: 17164146
Zuo X, Shen L, Issa JP, Moy O, Morris JS, Lippman SM, et al. 15-Lipoxygenase-1 transcriptional silencing by DNA methyltransferase-1 independently of DNA methylation. FASEB J. 2008;22:1981–92.
pubmed: 18198215
Snodgrass RG, Brune B. Regulation and functions of 15-lipoxygenases in human macrophages. Front Pharmacol. 2019;10:719.
pubmed: 31333453
pmcid: 6620526
Shankaranarayanan P, Chaitidis P, Kuhn H, Nigam S. Acetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is required for transcriptional activation of the 15-lipoxygenase-1 gene. J Biol Chem. 2001;276:42753–60.
pubmed: 11509556
Liu C, Xu D, Han H, Fan Y, Schain F, Xu Z, et al. Transcriptional regulation of 15-lipoxygenase expression by histone h3 lysine 4 methylation/demethylation. PLoS ONE. 2012;7: e52703.
pubmed: 23285160
pmcid: 3532411
Han H, Xu D, Liu C, Claesson HE, Bjorkholm M, Sjoberg J. Interleukin-4-mediated 15-lipoxygenase-1 trans-activation requires UTX recruitment and H3K27me3 demethylation at the promoter in A549 cells. PLoS ONE. 2014;9: e85085.
pubmed: 24465480
pmcid: 3896354
Zuo X, Morris JS, Broaddus R, Shureiqi I. 15-LOX-1 transcription suppression through the NuRD complex in colon cancer cells. Oncogene. 2009;28:1496–505.
pubmed: 19198625
pmcid: 2743348