ABSTRACT

Background

Knee osteoarthritis (OA) is one of the most common structural OA disorders globally. Incomplete understanding of the fundamental biological aspects of osteoarthritis underlies the current lack of effective treatment or disease modifying drugs.

Research Design and Methods

We implemented a systems approach by making use of the statistical network concepts in Weighted Gene Co-expression Analysis to reconstruct the organization of the core proteome network in chondrocytes obtained from OA patients and healthy individuals. Protein modules reflect groups of tightly co-ordinated changes in protein abundance across healthy and OA chondrocytes.

Results

The unbiased systems analysis identified extracellular matrix (ECM) mechanosensing and glycolysis as two modules that are most highly correlated with ΟΑ. The ECM module was enriched in the OA genetic risk factors tenascin-C (TNC) and collagen 11A1 (COL11A1), as well as in cartilage oligomeric matrix protein (COMP), a biomarker associated with cartilage integrity. Mapping proteins that are unique to OA or healthy chondrocytes onto the core interactome, which connects microenvironment sensing and regulation of glycolysis, identified differences in metabolic and anti-inflammatory adaptation.

Conclusion

The interconnection between cartilage ECM remodeling and metabolism is indicative of the dynamic chondrocyte states and their significance in osteoarthritis.

中文翻译：

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软骨细胞蛋白共合成网络分析将 ECM 机械传感与骨关节炎的代谢适应联系起来

摘要

背景

膝骨关节炎 (OA) 是全球最常见的结构性 OA 疾病之一。对骨关节炎基本生物学方面的不完全理解是目前缺乏有效治疗或疾病缓解药物的基础。

研究设计和方法

我们通过使用加权基因共表达分析中的统计网络概念来实施一种系统方法，以重建从 OA 患者和健康个体获得的软骨细胞中核心蛋白质组网络的组织。蛋白质模块反映了健康和 OA 软骨细胞中蛋白质丰度紧密协调的变化组。

结果

无偏系统分析将细胞外基质 (ECM) 机械传感和糖酵解确定为与 ΟΑ 最高度相关的两个模块。ECM 模块富含 OA 遗传风险因子肌腱蛋白-C (TNC) 和胶原蛋白 11A1 (COL11A1)，以及软骨寡聚基质蛋白 (COMP)，这是一种与软骨完整性相关的生物标志物。将 OA 或健康软骨细胞特有的蛋白质映射到核心相互作用组上，该核心相互作用组连接微环境感知和糖酵解调节，确定了代谢和抗炎适应的差异。

结论

软骨 ECM 重塑和代谢之间的相互联系表明了动态软骨细胞状态及其在骨关节炎中的意义。