Utility of circulating serum miRNAs as biomarkers of early cartilage degeneration in animal models of post-traumatic osteoarthritis and inflammatory arthritis

The purpose of this study was to identify potential serum microRNA (miRNA) biomarkers of cartilage degeneration comparing preclinical mouse models of post-traumatic osteoarthritis and inflammatory arthritis. Cartilage degeneration was induced in one knee of 10-12 week old male C57BL6 mice by surgical destabilization of the medial meniscus (DMM) or intra-articular injection of methylated-bovine-serum-albumin (AIA), with sham-operated or saline-injected control animals (n=6/treatment/time). Total serum RNA and knee joints were isolated at 1, 4 and 16 weeks post-induction. Cartilage degeneration was scored histologically. Serum miRNA expression profiling was performed using Agilent microarrays and validated by quantitative PCR.

本研究旨在通过对比创伤后骨关节炎与炎性关节炎的临床前小鼠模型，鉴定软骨退变相关的潜在血清微小RNA（microRNA, miRNA）生物标志物。本研究对10~12周龄的雄性C57BL6小鼠的单侧膝关节，分别通过内侧半月板失稳术（destabilization of the medial meniscus, DMM）或甲基化牛血清白蛋白（methylated-bovine-serum-albumin, AIA）关节腔内注射诱导软骨退变；同时设置假手术组与生理盐水注射对照组，每处理组、每时间点均配备6只实验动物。分别于造模后1周、4周及16周三个时间点采集小鼠血清总RNA并分离膝关节组织，通过组织病理学手段对软骨退变程度进行评分；同时采用安捷伦（Agilent）基因芯片开展血清miRNA表达谱分析，并通过定量PCR（quantitative PCR）验证表达结果。