4.4 Review

What can we learn from epigenetics in the year 2009?

期刊

CURRENT OPINION IN RHEUMATOLOGY
卷 22, 期 3, 页码 284-292

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BOR.0b013e3283389641

关键词

epigenetics; histone deacetylases; methylation; microRNA; rheumatoid arthritis; sirtuins; sumoylation

向作者/读者索取更多资源

Purpose of review Rheumatoid arthritis (RA) is a systemic, autoimmune disease resulting in the destruction of affected joints. Even though current therapies with biologics such as tumor necrosis factor-alpha blockers yield significant improvement for the patients, the disease is not curable yet. Therefore, we need novel strategies for better therapies. Recent findings The growing knowledge of epigenetics might give us new insights into the pathogenesis of autoimmune diseases. In the last year, several new findings about epigenetic modifications of gene expression were reported in different arthritides. These modifications describe changes in the expression of DNA that result from methylation, posttranslational modifications of the histone proteins, including acetylation/deacetylation, sumoylation, methylation and microRNAs. Most interestingly, these modifications seem to act in concert and are associated with the circadian metabolic rhythm of cells. Summary This review summarizes reports from the last year about epigenetic modifications of gene expression via acetylation/deacetylation, including sirtuins, sumoylation, methylation, microRNAs in all in rheumatoid arthritis and other arthritides, providing potential strategies for better therapies and encourages the development of specific epigenetic drugs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Cardiac & Cardiovascular Systems

TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal bymonoclonal TNFα antibodies

Alexander Akhmedov, Margot Crucet, Branko Simic, Simon Kraler, Nicole R. Bonetti, Caroline Ospelt, Oliver Distler, Adrian Ciurea, Luca Liberale, Matti Jauhiainen, Jari Metso, Melroy Miranda, Rose Cydecian, Lena Schwarz, Vera Fehr, Rita Zilinyi, Mohammad Amrollahi-Sharifabadi, Lydia Ntari, Niki Karagianni, Frank Ruschitzka, Reijo Laaksonen, Paul M. Vanhoutte, George Kollias, Giovanni G. Camici, Thomas F. Luescher

Summary: This study aimed to identify the molecular mechanism of endothelial dysfunction in a mouse model of rheumatoid arthritis (RA) and in patients with RA. The results showed that increased TNF alpha levels contribute to RA and endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NF kappa B/Arg2 pathway, resulting in reduced NO bioavailability and decreased cGMP levels. Anti-TNF alpha treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels.

CARDIOVASCULAR RESEARCH (2022)

Correction Rheumatology

Location, location, location: how the tissue microenvironment affects inflammation in RA (Feb, 10.1038/s41584-020-00570-2, 2021)

Christopher D. Buckley, Caroline Ospelt, Steffen Gay, Kim S. Midwood

Summary: A correction to this paper has been published and can be found at the provided link.

NATURE REVIEWS RHEUMATOLOGY (2021)

Review Rheumatology

Location, location, location: how the tissue microenvironment affects inflammation in RA

Christopher D. Buckley, Caroline Ospelt, Steffen Gay, Kim S. Midwood

Summary: This review discusses the role of synovial extracellular matrix in rheumatoid arthritis and how better understanding of it can improve disease diagnosis and new therapies. Current treatments for rheumatoid arthritis are not effective for many patients and cannot cure or prevent the disease. Lack of complete understanding of the pathogenesis of inflammatory joint disease is a major obstacle to developing better drugs.

NATURE REVIEWS RHEUMATOLOGY (2021)

Meeting Abstract Rheumatology

IDENTIFICATION OF FUNCTIONAL VARIANTS IN THE RHEUMATOID ARTHRITIS ASSOCIATED JAZF1 LOCUS IN SYNOVIAL FIBROBLASTS

M. Houtman, X. Ge, A. Mcgovern, K. Klein, G. Orozco, M. Frank Bertoncelj, M. Marks, O. Distler, P. Martin, S. Eyre, C. Ospelt

ANNALS OF THE RHEUMATIC DISEASES (2021)

Meeting Abstract Rheumatology

HOMEOBOX D TRANSCRIPTION FACTORS SHAPE DIFFERENTIAL JOINT ENVIRONMENT BETWEEN ANTERIOR FINGER JOINTS AND THUMB

M. Mirrahimi, K. Klein, M. Houtman, M. Maciukiewicz, M. Frank Bertoncelj, A. Juengel, M. Berli, M. Marks, O. Distler, C. Ospelt

ANNALS OF THE RHEUMATIC DISEASES (2021)

Article Immunology

Individual functions of the histone acetyl transferases CBP and p300 in regulating the inflammatory response of synovial fibroblasts

Monika Krosel, Marcel Gabathuler, Malgorzata Maciukiewicz, Larissa Moser, Gideon Isaac Lee, Miriam Marks, Matija Tomsic, Oliver Distler, Caroline Ospelt, Kerstin Klein

Summary: In rheumatoid arthritis, chromatin remodeling and histone 3 lysine 27 acetylation are associated with sustained inflammatory responses in synovial fibroblasts. Writer proteins CBP and p300 have overlapping but distinct regulatory functions in controlling gene expression, with p300 being the major HAT for H3K27ac. Inhibition of CBP/p300 mirrors effects seen with p300 silencing, suggesting that inhibitors targeting these proteins may not be sufficient as anti-inflammatory drugs.

JOURNAL OF AUTOIMMUNITY (2021)

Article Biochemistry & Molecular Biology

Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells

Octavio Morante-Palacios, Laura Ciudad, Raphael Micheroli, Carlos de la Calle-Fabregat, Tianlu Li, Gisela Barbisan, Miranda Houtman, Sam G. Edalat, Mojca Frank-Bertoncelj, Caroline Ospelt, Esteban Ballestar

Summary: The study revealed that MAFB plays a critical role in the acquisition of tolerogenic properties in DCs in synergy with GR. MAFB interacts with TET2 and binds to genomic loci involved in the demethylation process in tolDCs. Knockdown of MAFB abolishes the tolerogenic properties of tolDCs, reversing the specific DNA demethylation and gene upregulation.

NUCLEIC ACIDS RESEARCH (2022)

Editorial Material Rheumatology

EMerging EULAR NETwork (EMEUNET): a remarkable foundation for the future

Alessia Alunno, Felice Rivellese, Kim Lauper, Daniel Aletaha, Maya H. Buch, Laure Gossec, Peter Mandl, Pedro M. Machado, Caroline Ospelt, Anna Molto, Sofia Ramiro, Elena Nikiphorou, Alexandre Sepriano

RMD OPEN (2021)

Article Immunology

A brief history of epigenetics

Caroline Ospelt

Summary: In the past 70 years, the study of epigenetics has transitioned from being a research curiosity to being one of the most hyped biological concepts. Today, the modulation of epigenetics through behavioral changes is promoted as a cure for diseases. The concept that environmental influences can cause stable and heritable changes in gene expression has been enthusiastically embraced in the field of medical biology.

IMMUNOLOGY LETTERS (2022)

Letter Rheumatology

Prediction of histology by B-mode and PD-mode ultrasound across different joint locations and diseases

Raphael Micheroli, Chantal Pauli, Kristina Buerki, Philipp Rossbach, Oliver Distler, Caroline Ospelt, Adrian Ciurea

RMD OPEN (2022)

Editorial Material Immunology

A common activator of tissue-remodeling fibroblasts across tissues

Caroline Ospelt

Summary: ETS1 regulates tissue-remodeling properties of specific fibroblast subtypes in synovium, gut, and cancer, making it a novel therapeutic target for modulating pathogenic fibroblast activation.

NATURE IMMUNOLOGY (2022)

Review Rheumatology

Site of invasion revisited: epigenetic drivers of joint destruction in RA

Caroline Ospelt

Summary: New analytical methods and the increasing availability of synovial biopsies have shed light on the role of synovial fibroblasts (SFs) in rheumatoid arthritis (RA). Recent studies have revealed heterogeneity and propagation of SFs in RA, expanding our understanding of their active involvement in the invasion of synovium into cartilage. This review provides an overview of the processes occurring at sites of invasive synovial tissue growth in RA by integrating old and new evidence.

ANNALS OF THE RHEUMATIC DISEASES (2023)

Article Cell Biology

Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts

Monika Krosel, Larissa Moser, Miranda Houtman, Jasna Friscic, Matija Tomsic, Oliver Distler, Markus H. Hoffmann, Caroline Ospelt, Kerstin Klein

Summary: BET proteins regulate gene transcription by binding to acetylated histone side chains. The BET inhibitor I-BET151 not only prevents the reading of acetylated histones, but also influences overall chromatin organization.
Letter Rheumatology

Allele-specific protein binding within the CD40 locus in human synovial fibroblasts and immune cells

Larissa Moser, Katerina Laskari, Caroline Ospelt, Miranda Houtman

RMD OPEN (2023)

Article Biotechnology & Applied Microbiology

Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability

Xiangyu Ge, Mojca Frank-Bertoncelj, Kerstin Klein, Amanda McGovern, Tadeja Kuret, Miranda Houtman, Blaz Burja, Raphael Micheroli, Chenfu Shi, Miriam Marks, Andrew Filer, Christopher D. Buckley, Gisela Orozco, Oliver Distler, Andrew P. Morris, Paul Martin, Stephen Eyre, Caroline Ospelt

Summary: The study reveals the potential causal role of fibroblast-like synoviocytes (FLS) in the genetic susceptibility for rheumatoid arthritis (RA), accounting for up to a quarter of RA heritability. Activation of FLS may impact the expression of genes like TNFAIP3 and cellular proliferation.

GENOME BIOLOGY (2021)

暂无数据