Osteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients. We compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study for cartilage degeneration across 170 patients and separately in 96 women and 74 men. We reveal widespread epigenetic differences with enrichments of nervous system and apoptosis-related processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways. Together, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression.

中文翻译：

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原发性软骨骨关节炎等级之间的表观基因组差异


骨关节炎是一种常见且复杂的关节疾病，女性患病率更高，疾病严重程度更高。在这里，我们研究了骨关节炎患者原代软骨细胞的全基因组甲基化谱。我们比较了来自接受膝关节置换手术的骨关节炎患者匹配的宏观完整（低级别）和降解（高级别）骨关节炎软骨样本的全基因组甲基化谱。我们对 170 名患者（分别为 96 名女性和 74 名男性）进行了一项软骨退变的全表观基因组关联研究。我们揭示了神经系统和细胞凋亡相关过程丰富的广泛表观遗传差异。我们进一步确定了性别之间的实质性相似性，以及性别特异性标记和途径。我们共同提供了迄今为止最大的原发性软骨全基因组甲基化图谱，并增强了对骨关节炎进展的表观遗传过程的性别特异性见解。