Rego-Pérez Ignacio, Durán-Sotuela Alejandro, Ramos-Louro Paula, Blanco Francisco J
Grupo de Investigación en Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
Front Genet. 2020 Jan 17;10:1335. doi: 10.3389/fgene.2019.01335. eCollection 2019.
During recent years, the significant influence of mitochondria on osteoarthritis (OA), the most common joint disease, has been consistently demonstrated. Not only mitochondrial dysfunction but also mitochondrial genetic polymorphisms, specifically the mitochondrial DNA haplogroups, have been shown to have an important influence on different OA-related features, including the prevalence, severity, incidence, and progression of the disease. This influence could probably be mediated by the role of mitochondria in the regulation of different processes involved in the pathogenesis of OA, such as energy production, the generation of reactive oxygen and nitrogen species, apoptosis, and inflammation. The regulation of these processes is at least partially controlled by the bi-directional communication between the nucleus and mitochondria, which permits the regulation of adaptation to a wide range of stressors and the maintenance of cellular homeostasis. This bi-directional communication consists of an "anterograde regulation" by which the nucleus regulates mitochondrial biogenesis and activity and a "retrograde regulation" by which both mitochondria and mitochondrial genetic variation exert a regulatory signaling control over the nuclear epigenome, which leads to the modulation of nuclear genes. Throughout this mini review, we will describe the evidence that demonstrates the profound influence of the mitochondrial genetic background in the pathogenesis of OA, as well as its influence on the nuclear DNA methylome of the only cell type present in the articular cartilage, the chondrocyte. This evidence leads to serious consideration of the mitochondrion as an important therapeutic target in OA.
近年来，线粒体对骨关节炎（OA）这一最常见的关节疾病的显著影响已得到持续证实。不仅线粒体功能障碍，而且线粒体基因多态性，特别是线粒体DNA单倍群，已被证明对不同的OA相关特征具有重要影响，包括疾病的患病率、严重程度、发病率和进展。这种影响可能是由线粒体在OA发病机制中涉及的不同过程的调节作用介导的，如能量产生、活性氧和氮物种的产生、细胞凋亡和炎症。这些过程的调节至少部分受细胞核与线粒体之间的双向通讯控制，这种通讯允许对广泛应激源的适应调节和细胞内稳态的维持。这种双向通讯包括“正向调节”，即细胞核调节线粒体生物发生和活性，以及“逆向调节”，即线粒体和线粒体基因变异对核表观基因组施加调节信号控制，从而导致核基因的调节。在这篇综述中，我们将描述相关证据，这些证据证明线粒体遗传背景在OA发病机制中的深远影响，以及其对关节软骨中唯一存在的细胞类型——软骨细胞的核DNA甲基化组的影响。这些证据促使人们认真考虑将线粒体作为OA的一个重要治疗靶点。
