DNA Methylation in Osteoarthritis.
DNA Methylation in Osteoarthritis.
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DOI：
10.2174/1389202916666150817212711
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发表时间：
2015-12
期刊：
影响因子：
2.6
通讯作者：
Meulenbelt I
中科院分区：
文献类型：
--
作者：
den Hollander W;Meulenbelt I
骨关节炎（OA）是一种常见的关节疾病，主要表现为关节软骨的退化和钙化。目前，除了缓解疼痛之外，没有其他有效的治疗方法，患者最终需要对受影响的关节进行置换手术。关节软骨细胞是关节软骨中的单细胞类型，在疾病进展过程中表现出转录谱的改变，并经历与生长板软骨细胞中明显的终末分化途径相似的表型变化。因此，鉴于其在调节基因表达和维持细胞表型方面的突出功能，CpG二核苷酸的DNA甲基化在OA的背景下得到了深入研究。越来越多的研究发表了针对已知在OA病理生理中起作用的基因的靶向方法。因此，很明显OA反应性DNA甲基化变化似乎介导了疾病相关的异常基因表达。此外，已建立的OA易感等位基因如GDF5和DIO2似乎通过DNA甲基化和各自的病理生理表达变化赋予OA风险。近年来，骨性关节炎受影响关节软骨DNA甲基化的全基因组谱分析已成为解决其整体表观遗传变化的有力工具，这导致了假定的患者亚群以及一般骨性关节炎相关途径的鉴定。
Osteoarthritis (OA) is a prevalent disease of articular joints and primarily characterized by degradation and calcification of articular cartilage. Presently, no effective treatment other than pain relief exists and patients ultimately need to undergo replacement surgery of the affected joint. During disease progression articular chondrocytes, the single cell type present in articular cartilage, show altered transcriptional profiles and undergo phenotypic changes that resemble the terminal differentiation route apparent in growth plate chondrocytes. Hence, given its prominent function in both regulating gene expression and maintaining cellular phenotypes, DNA methylation of CpG dinucleotides is intensively studied in the context of OA. An increasing number of studies have been published that employed a targeted approach on genes known to play a role in OA pathophysiology. As of such, it has become clear that OA responsive DNA methylation changes seem to mediate disease associated aberrant gene expression. Furthermore, established OA susceptibility alleles such as GDF5 and DIO2 appear to confer OA risk via DNA methylation and respective pathophysiological expression changes. In more recent years, genome wide profiling of DNA methylation in OA affected articular cartilage has emerged as a powerful tool to address the epigenetic changes in their entirety, which has resulted in the identification of putative patient subgroups as well as generic OA associated pathways.