Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes
Abstract 3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric O...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2017
|
Materias: | |
Acceso en línea: | https://doaj.org/article/c493f3d217a94a09bb3338b657f3985e |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:c493f3d217a94a09bb3338b657f3985e |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:c493f3d217a94a09bb3338b657f3985e2021-12-02T15:04:59ZAnti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes10.1038/s41598-017-06913-62045-2322https://doaj.org/article/c493f3d217a94a09bb3338b657f3985e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06913-6https://doaj.org/toc/2045-2322Abstract 3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray. DZNep inhibited SAHH activity and was not toxic. It counteracted NO, PGE2 and MMP release, and reduced MAPK activation induced by IL-1β. By whole-transcriptome analysis, we identified that DNZep counteracts the effect of IL-1β on the expression of 81 protein-coding genes, including CITED2, an MMP inhibitor. These genes are organized in a protein-protein network centred on EGR1, which is known to functionally interact with EZH2. Gene ontologies enrichment analysis confirmed that DZNep counteracts IL-1β-induced expression of genes involved in cartilage matrix breakdown (MMPs and ADAMTS). In addition, DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA.Juliette Aury-LandasCéline BazilleLyess AllasSara BouhoutChristophe ChesneauSylvain LeclercqKarim BoumédieneCatherine BaugéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Juliette Aury-Landas Céline Bazille Lyess Allas Sara Bouhout Christophe Chesneau Sylvain Leclercq Karim Boumédiene Catherine Baugé Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
description |
Abstract 3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray. DZNep inhibited SAHH activity and was not toxic. It counteracted NO, PGE2 and MMP release, and reduced MAPK activation induced by IL-1β. By whole-transcriptome analysis, we identified that DNZep counteracts the effect of IL-1β on the expression of 81 protein-coding genes, including CITED2, an MMP inhibitor. These genes are organized in a protein-protein network centred on EGR1, which is known to functionally interact with EZH2. Gene ontologies enrichment analysis confirmed that DZNep counteracts IL-1β-induced expression of genes involved in cartilage matrix breakdown (MMPs and ADAMTS). In addition, DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA. |
format |
article |
author |
Juliette Aury-Landas Céline Bazille Lyess Allas Sara Bouhout Christophe Chesneau Sylvain Leclercq Karim Boumédiene Catherine Baugé |
author_facet |
Juliette Aury-Landas Céline Bazille Lyess Allas Sara Bouhout Christophe Chesneau Sylvain Leclercq Karim Boumédiene Catherine Baugé |
author_sort |
Juliette Aury-Landas |
title |
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
title_short |
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
title_full |
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
title_fullStr |
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
title_full_unstemmed |
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes |
title_sort |
anti-inflammatory and chondroprotective effects of the s-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin a, in human articular chondrocytes |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/c493f3d217a94a09bb3338b657f3985e |
work_keys_str_mv |
AT julietteaurylandas antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT celinebazille antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT lyessallas antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT sarabouhout antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT christophechesneau antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT sylvainleclercq antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT karimboumediene antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes AT catherinebauge antiinflammatoryandchondroprotectiveeffectsofthesadenosylhomocysteinehydrolaseinhibitor3deazaneplanocinainhumanarticularchondrocytes |
_version_ |
1718388980861370368 |