Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients

Huber, Lars C; Brock, Matthias; Hemmatazad, Hossein; Giger, Olivier; Moritz, F.; Trenkmann, Michelle; Distler, Jörg H W; Gay, Renate E.; Kolling, Christoph; Moch, Holger; Michel, Beat A.; Gay, Steffen; Distler, Oliver; Jüngel, Astrid

doi:10.1002/art.22512

Cited by 190 publications

(150 citation statements)

References 26 publications

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“…A recently published report also provides evidence of histone hyperacetylation in synovial tissue samples from animals with a RA-like condition compared to animals with osteoarthritis (OA). Furthermore, the authors find the activity of HDACs to be about two-fold lower in synovial extracts from RA patients compared to OA patients [8].…”

Section: Rheumatoid Arthritismentioning

confidence: 97%

Epigenetics in autoimmune disorders: Highlights of the 10th Sjögren's Syndrome Symposium

Lu¹,

Renaudineau²,

Cha

et al. 2010

Autoimmunity Reviews

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During the 10th International Symposium on Sjögren's Syndrome held in Brest, France, from October 1-3, 2009 (http://www.sjogrensymposium-brest2009.org), the creation of an international epigenetic autoimmune group has been proposed to establish gold standards and to launch collaborative studies. During this "epigenetics session", leading experts in the field presented and discussed the most recent developments of this topic in Sjögren's Syndrome research. The "Brest epigenetic task force" was born and has scheduled a meeting in Ljubljana, Slovenia during the 7th Autoimmunity congress in May 2010.The following is a report of that session.  Increased activity and destructive potential of synovial fibroblasts in rheumatoid arthritis is due in part to the deregulation of epigenetic factors. Development of an epigenetic bank and the establishment of gold standards in an epigenetic consortium to analyse epigenetic modifications are needed. Epigenetic alterations in autoimmune diseases could be used as prognostic/diagnostic tools and markers of immune cell activation.2

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Section: Rheumatoid Arthritismentioning

confidence: 97%

Epigenetics in autoimmune disorders: Highlights of the 10th Sjögren's Syndrome Symposium

Lu¹,

Renaudineau²,

Cha

et al. 2010

Autoimmunity Reviews

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“…To investigate whether this is the case, we performed chromatin immunoprecipitation using anti- It has been described by Huber et al that in RA synovial tissues the balance of HAT/HDAC activity is strongly shifted towards histone acetylation (8). In addition, it has been shown that several HDAC inhibitors had rather beneficial effects in the animal models, where they were shown to improve joint swelling, synovial inflammation, bone and cartilage destruction, downregulated the production of VEGF, blocked angiogenesis and promoted cell cycle arrest and apoptosis (25)(26)(27)(28).…”

Section: Overexpression Of Senp1 Leads To An Accumulation Of Histone mentioning

confidence: 99%

“…Recently, our group could show that in RA synovial tissues the balance of activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is strongly shifted towards histone acetylation (8), which is associated with increased transcription rates (9,10). This posttranslational modification of histones belongs to epigenetic modifications regulating gene expression and offers us new mechanism for therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Epigenetics and rheumatoid arthritis: The role of SENP1 in the regulation of MMP-1 expression

Maciejewska-Rodrigues¹,

Karouzakis²,

Strietholt³

et al. 2010

Journal of Autoimmunity

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The aggressive phenotype of RA synovial fibroblasts (RASF) is characterised by the increased expression of matrix metalloproteinase (MMP)-1 as well as the small ubiquitin like modifier (SUMO)-1 and decreased expression of SUMO-specific protease SENP1. Since we showed an increased activity of acetyltransferases in this autoimmune disease, we wanted to analyse whether this affects the expression of MMP-1 and can be reversed by the reconstitution of SENP1.In RASF, the acetylation of histone H4 was significantly increased in the distal region of the MMP-1 promoter by 274 ± 36% compared to OASF. Most interestingly, overexpression of SENP1 in RASF decreased acetylation specifically in this region by 51 ± 0.5% and globally by 73 ± 11%. Furthermore, the overexpression of SENP1 resulted in a downregulation of MMP-1 at both the mRNA (58  7%) and protein levels (28 ± 6%), significantly reduced the invasiveness of RASF (from 34  9% to 2  2%) and led to an accumulation of histone deacetylase 4 (HDAC4) on the MMP-1 promoter (197 ± 36%). Interestingly, SENP1 failed to modulate the expression of MMP-1 in the cells silenced for HDAC4. This is the first study linking the SUMOylation pathway and the production of MMP-1 to an epigenetic control mechanism mediated through histone acetylation which has a functional consequence for the invasiveness of RASF.

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“…The histone deacetylase activity in synovial tissues from patients with RA was approximately 2-fold lower than that in synovial tissues from patients with osteoarthritis or from normal controls [33] . A single intravenous injection of depsipeptide (FK228), a histone deacetylase inhibitor, inhibited joint swelling, synovial inflammation and subsequent bone and cartilage destruction in mice with autoantibody-mediated arthritis (AMA) [34] .…”

Section: Discussionmentioning

confidence: 71%

Hypomethylation of proximal CpG motif of interleukin-10 promoter regulates its expression in human rheumatoid arthritis

Cong

et al. 2011

Acta Pharmacol Sin

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Aim:The promoter of human interleukin-10 (IL10), a cytokine crucial for suppressing inflammation and regulating immune responses, contains an interspecies-conserved sequence with CpG motifs. The aim of this study was to investigate whether methylation of CpG motifs could regulate the expression of IL10 in rheumatoid arthritis (RA). Methods: Bioinformatic analysis was conducted to identify the interspecies-conserved sequence in human, macaque and mouse IL10 genes. Peripheral blood mononuclear cells (PBMCs) from 20 RA patients and 20 health controls were collected. The PBMCs from 6 patients were cultured in the presence or absence of 5-azacytidine (5 μmol/L). The mRNA and protein levels of IL10 were examined using RT-PCR and ELISA, respectively. The methylation of CpGs in the IL10 promoter was determined by pyrosequencing. Chromatin immunoprecipitation (ChIP) assays were performed to detect the cyclic AMP response element-binding protein (CREB)-DNA interactions. Results: One interspecies-conserved sequence was found within the IL10 promoter. The upstream CpGs at -408, -387, -385, and -355 bp were hypermethylated in PBMCs from both the RA patients and healthy controls. In contrast, the proximal CpG at -145 was hypomethylated to much more extent in the RA patients than in the healthy controls (P=0.016), which was correlated with higher IL10 mRNA and serum levels. In the 5-azacytidine-treated PBMCs, the CpG motifs were demethylated, and the expression levels of IL10 mRNA and protein was significantly increased. CHIP assays revealed increased phospho-CREB binding to the IL10 promoter. Conclusion: The methylation of the proximal CpGs in the IL10 promoter may regulate gene transcription in RA.

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Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients

Cited by 190 publications

References 26 publications

Epigenetics in autoimmune disorders: Highlights of the 10th Sjögren's Syndrome Symposium

Epigenetics in autoimmune disorders: Highlights of the 10th Sjögren's Syndrome Symposium

Epigenetics and rheumatoid arthritis: The role of SENP1 in the regulation of MMP-1 expression

Hypomethylation of proximal CpG motif of interleukin-10 promoter regulates its expression in human rheumatoid arthritis

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