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骨关节炎中的DNA甲基化与非编码RNA:最新发现与方法学进展

DNA methylation and noncoding RNA in OA: Recent findings and methodological advances.

作者信息

Izda Vladislav, Martin Jake, Sturdy Cassandra, Jeffries Matlock A

机构信息

Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, Oklahoma City, OK, USA.

University of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, And Allergy, Oklahoma City, OK, USA.

出版信息

Osteoarthr Cartil Open. 2021 Dec;3(4). doi: 10.1016/j.ocarto.2021.100208. Epub 2021 Aug 14.

Abstract

INTRODUCTION

Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by progressive loss of joint function. Historically, it has been characterized as a disease caused by mechanical trauma, so-called 'wear and tear'. Over the past two decades, it has come to be understood as a complex systemic disorder involving gene-environmental interactions. Epigenetic changes have been increasingly implicated. Recent improvements in microarray and next-generation sequencing (NGS) technologies have allowed for ever more complex evaluations of epigenetic aberrations associated with the development and progression of OA.

METHODS

A systematic review was conducted in the Pubmed database. We curated studies that presented the results of DNA methylation and noncoding RNA research in human OA and OA animal models since 1985.

RESULTS

Herein, we discuss recent findings and methodological advancements in OA epigenetics, including a discussion of DNA methylation, including microarray and NGS studies, and noncoding RNAs. Beyond cartilage, we also highlight studies in subchondral bone and peripheral blood mononuclear cells, which highlight widespread and potentially clinically important alterations in epigenetic patterns seen in OA patients. Finally, we discuss epigenetic editing approaches in the context of OA.

CONCLUSIONS

Although a substantial body of literature has already been published in OA, much is still unknown. Future OA epigenetics studies will no doubt continue to broaden our understanding of underlying pathophysiology and perhaps offer novel diagnostics and/or treatments for human OA.

摘要

引言

骨关节炎(OA)是一种慢性肌肉骨骼疾病,其特征是关节功能逐渐丧失。从历史上看,它被认为是一种由机械创伤引起的疾病,即所谓的“磨损”。在过去的二十年里,人们逐渐认识到它是一种涉及基因-环境相互作用的复杂系统性疾病。表观遗传变化越来越受到关注。微阵列和下一代测序(NGS)技术的最新进展使得对与OA的发生和发展相关的表观遗传异常进行更复杂的评估成为可能。

方法

在PubMed数据库中进行了系统综述。我们筛选了自1985年以来发表的有关人类OA和OA动物模型中DNA甲基化和非编码RNA研究结果的文献。

结果

在此,我们讨论OA表观遗传学的最新发现和方法学进展,包括对DNA甲基化(包括微阵列和NGS研究)和非编码RNA的讨论。除了软骨,我们还重点介绍了对软骨下骨和外周血单核细胞的研究,这些研究突出了OA患者表观遗传模式中广泛存在且可能具有临床重要性的改变。最后,我们在OA的背景下讨论表观遗传编辑方法。

结论

尽管已经有大量关于OA的文献发表,但仍有许多未知之处。未来OA表观遗传学研究无疑将继续拓宽我们对潜在病理生理学的理解,并可能为人类OA提供新的诊断方法和/或治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4248/9718210/836f56bef512/gr1.jpg

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