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骨关节炎的表观遗传学:新的焦点。

Epigenetics in osteoarthritis: Novel spotlight.

机构信息

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Physiol. 2019 Aug;234(8):12309-12324. doi: 10.1002/jcp.28020. Epub 2019 Jan 19.

Abstract

Osteoarthritis (OA) is the most common type of arthritis and no longer is considered as an absolute consequence of joint mechanical use (wear and tear); rather recent data demonstrate the pivotal role of inflammatory mediators in the development and progression of this disease. This multifactorial disease results from several environmental and inherited factors. Genetic cannot solely explain all the contribution share of inheritance and, this way, it is speculated that epigenetics can play a role, too. Moreover, environmental factors can induce local epigenetic changes. The epigenetic contribution to OA pathogenesis occurs at all of its levels, DNA methylation, histone modification, microRNA, and long noncoding RNA. In fact, during early phases of OA pathogenesis, environmental factors employ epigenetic mechanisms to provide a positive feedback for the OA-related pathogenic mechanisms and pathways with an ultimate outcome of a well-established clinical OA. These epigenetic changes stay during clinical disease and prevent the body natural healing and regenerative processes to work properly, resulting in an incurable disease condition. In this review article, we aimed to have an overview on the studies performed with regard to understanding the role of epigenetics in the etiopathogenesis of OA and highlighted the importance of such kind of regulatory mechanisms within this context.

摘要

骨关节炎(OA)是最常见的关节炎类型,不再被认为是关节机械使用(磨损)的绝对后果;相反,最近的数据表明炎症介质在这种疾病的发展和进展中起着关键作用。这种多因素疾病是由几个环境和遗传因素引起的。遗传因素不能单独解释所有的遗传贡献份额,因此,有人推测表观遗传学也可能发挥作用。此外,环境因素可以诱导局部表观遗传变化。表观遗传对 OA 发病机制的贡献发生在其所有层面,包括 DNA 甲基化、组蛋白修饰、microRNA 和长非编码 RNA。事实上,在 OA 发病机制的早期阶段,环境因素利用表观遗传机制为 OA 相关的发病机制和途径提供正向反馈,最终导致明确的临床 OA。这些表观遗传变化在临床疾病期间持续存在,并阻止身体正常的愈合和再生过程,导致不可治愈的疾病状态。在这篇综述文章中,我们旨在概述关于理解表观遗传学在 OA 发病机制中的作用的研究,并强调这种调节机制在这种情况下的重要性。

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