Arthritis Program, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
JCI Insight. 2018 Sep 6;3(17). doi: 10.1172/jci.insight.121630.
The disabling degenerative disease osteoarthritis (OA) is prevalent among the global population. Articular cartilage degeneration is a central feature of OA; therefore, a better understanding of the mechanisms that maintain cartilage homeostasis is vital for developing effective therapeutic interventions. MicroRNAs (miRs) modulate cell signaling pathways and various processes in articular cartilage via posttranscriptional repression of target genes. As dysregulated miRs frequently alter the homeostasis of articular cartilage, modulating select miRs presents a potential therapeutic opportunity for OA. Here, we review key miRs that have been shown to modulate cartilage-protective or -destructive mechanisms and signaling pathways. Additionally, we use an integrative computational biology approach to provide insight into predicted miR gene targets that may contribute to OA pathogenesis, and highlight the complexity of miR signaling in OA by generating both unique and overlapping gene targets of miRs that mediate protective or destructive effects. Early OA detection would enable effective prevention; thus, miRs are being explored as diagnostic biomarkers. We discuss these ongoing efforts and the applicability of miR mimics and antisense inhibitors as potential OA therapeutics.
致残退行性疾病骨关节炎（OA）在全球人群中普遍存在。关节软骨退化是 OA 的一个主要特征；因此，更好地了解维持软骨稳态的机制对于开发有效的治疗干预措施至关重要。microRNAs（miRs）通过靶向基因的转录后抑制来调节细胞信号通路和关节软骨中的各种过程。由于失调的 miRs 经常改变关节软骨的稳态，因此调节特定的 miRs 为 OA 提供了潜在的治疗机会。在这里，我们综述了已被证明可调节软骨保护或破坏机制和信号通路的关键 miRs。此外，我们还使用整合计算生物学方法深入了解可能导致 OA 发病机制的预测 miR 基因靶标，并通过生成介导保护或破坏作用的 miRs 的独特和重叠基因靶标来突出 OA 中 miR 信号的复杂性。早期 OA 检测将能够实现有效预防；因此，miRs 正在被探索作为诊断生物标志物。我们讨论了这些正在进行的努力以及 miR 模拟物和反义抑制剂作为潜在 OA 治疗剂的适用性。
