Zhang Mingcai, Wang Jinxi
Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA.
Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA ; Department of Biochemistry & Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Genes Dis. 2015 Mar;2(1):69-75. doi: 10.1016/j.gendis.2014.12.005.
Osteoarthritis (OA) is the most common form of joint disease and the leading cause of chronic disability in middle-aged and older populations. The development of disease-modifying therapy for OA currently faces major obstacles largely because the regulatory mechanisms for the function of joint tissue cells remain unclear. Previous studies have found that the alterations in gene expression of specific transcription factors (TFs), pro- or anti-inflammatory cytokines, matrix proteinases and extracellular matrix (ECM) proteins in articular cartilage may be involved in the development of OA. However, the regulatory mechanisms for the expression of those genes in OA chondrocytes are largely unknown. The recent advances in epigenetic studies have shed lights on the importance of epigenetic regulation of gene expression in the development of OA. In this review, we summarize and discuss the recent studies on the regulatory roles of various epigenetic mechanisms in the expression of genes for specific TFs, cytokines, ECM proteins and matrix proteinases, as well the significance of these epigenetic mechanisms in the pathogenesis of OA.
骨关节炎(OA)是最常见的关节疾病形式,也是中老年人群慢性残疾的主要原因。目前,针对OA的疾病修饰疗法的开发面临重大障碍,这主要是因为关节组织细胞功能的调节机制仍不清楚。先前的研究发现,关节软骨中特定转录因子(TFs)、促炎或抗炎细胞因子、基质蛋白酶和细胞外基质(ECM)蛋白的基因表达改变可能与OA的发展有关。然而,OA软骨细胞中这些基因表达的调节机制在很大程度上尚不清楚。表观遗传学研究的最新进展揭示了基因表达的表观遗传调控在OA发展中的重要性。在这篇综述中,我们总结并讨论了近期关于各种表观遗传机制在特定TFs、细胞因子、ECM蛋白和基质蛋白酶基因表达中的调节作用的研究,以及这些表观遗传机制在OA发病机制中的意义。