Research Division, The Hospital for Special Surgery, Weill Cornell Medical College, New York, NY 10021, USA.
Trends Mol Med. 2012 Feb;18(2):109-18. doi: 10.1016/j.molmed.2011.11.005. Epub 2011 Dec 17.
Osteoarthritis (OA) is a multifactorial disease subject to the effects of many genes and environmental factors. Alterations in the normal pattern of chondrocyte gene control in cartilage facilitate the onset and progression of OA. Stable changes in patterns of gene expression, not associated with alterations in DNA sequences, occur through epigenetic changes, including DNA methylation, histone modifications, and alterations in chromatin structure, as well as by microRNA (miRNA)-mediated mechanisms. Moreover, the ability of the host to repair damaged cartilage is reflected in alterations in gene control circuits, suggestive of an epigenetic and miRNA-dependent tug-of-war between tissue homeostasis and OA disease pathogenesis. Herein, we summarize epigenetic and miRNA-mediated mechanisms impacting on OA progression and in this context offer potential therapeutic strategies for OA treatment.
骨关节炎(OA)是一种多因素疾病,受到许多基因和环境因素的影响。软骨中正常的软骨细胞基因控制模式的改变促进了 OA 的发生和发展。表观遗传改变,包括 DNA 甲基化、组蛋白修饰和染色质结构改变,以及 microRNA(miRNA)介导的机制,导致了与 DNA 序列改变无关的基因表达模式的稳定变化。此外,宿主修复受损软骨的能力反映在基因控制回路的改变上,这表明组织平衡和 OA 发病机制之间存在着表观遗传和 miRNA 依赖性的拉锯战。在此,我们总结了影响 OA 进展的表观遗传和 miRNA 介导的机制,并在此背景下为 OA 的治疗提供了潜在的治疗策略。