Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis models.

IF 4 3区 医学 Q2 CELL BIOLOGY Disease Models & Mechanisms Pub Date : 2024-10-01 Epub Date: 2024-10-21 DOI:10.1242/dmm.050583
Sophie J Gilbert, Jamie Soul, Yao Hao, Hua Lin, Katarzyna A Piróg, Jonathan Coxhead, Krutik Patel, Matt J Barter, David A Young, Emma J Blain
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Abstract

Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here, skeletally mature C57Bl6 mice were subjected to either rapid-onset non-surgical mechanical rupture of the anterior cruciate ligament (ACL) or to surgical destabilisation of the medial meniscus (DMM). Transcriptome profiling of micro-dissected cartilage at day 7 or day 42 following ACL or DMM procedure, respectively, showed that the two models were comparable and highly correlative. Gene ontology (GO) enrichment analysis identified similarly enriched pathways that were overrepresented by anabolic terms. To address the transcriptome changes more completely in the ACL model, we also performed small RNA sequencing, describing the first microRNA profile of this model. miR-199-5p was amongst the most abundant, yet differentially expressed, microRNAs, and its inhibition in primary human chondrocytes led to a transcriptome response that was comparable to that observed in both human 'OA damaged vs intact cartilage' and murine DMM cartilage datasets. We also experimentally verified CELSR1, GIT1, ECE1 and SOS2 as novel miR-199-5p targets. Together, these data support the use of the ACL rupture model as a non-invasive companion to the DMM model.

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创伤后骨关节炎小鼠模型关节软骨的转录组比较分析
创伤后骨关节炎(PTOA)的动物模型再现了在人类创伤后骨关节炎中观察到的病理变化。在这里,对骨骼成熟的 C57Bl6 小鼠进行了快速发病、非手术、机械性前十字韧带(ACL)断裂或手术破坏内侧半月板(DMM)模型。分别在 ACL 和 DMM 术后第 7 天和第 42 天对显微解剖的软骨进行转录组图谱分析,结果表明这两种模型具有可比性和高度相关性(Spearman R =0.82,p
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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