Transcriptomic analyses of joint tissues during osteoarthritis development in a rat model reveal dysregulated mechanotransduction and extracellular matrix pathways

被引：12

作者：

Hu, Y. ^{[1
,2
]}

Li, K. ^{[1
]}

Swahn, H. ^{[1
]}

Ordoukhanian, P. ^{[3
]}

Head, S. R. ^{[3
]}

Natarajan, P. ^{[3
]}

Woods, A. K. ^{[4
]}

Joseph, S. B. ^{[4
]}

Johnson, K. A. ^{[4
]}

Lotz, M. K. ^{[1
]}

机构：

[1] Scripps Res, Dept Mol Med, La Jolla, CA 92037 USA

[2] Fudan Univ, Huashan Hosp, Dept Radiol, Shanghai, Peoples R China

[3] Scripps Res, Ctr Computat Biol & Bioinformat & Genom Core, La Jolla, CA 92037 USA

[4] Calibr Div Scripps Res, La Jolla, CA 92037 USA

来源：

OSTEOARTHRITIS AND CARTILAGE | 2023年 / 31卷 / 02期

关键词：

Osteoarthritis; RNA sequencing; Mechanotransduction; GENE-EXPRESSION; ARTICULAR-CARTILAGE; SUBCHONDRAL BONE; DAMAGE; PAIN; ANGIOGENESIS; CHONDROCYTES; MENISCUS; CHANNELS; TRPV4;

D O I：

10.1016/j.joca.2022.10.003

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

Objective: Transcriptomic changes in joint tissues during the development of osteoarthritis (OA) are of interest for the discovery of biomarkers and mechanisms of disease. The objective of this study was to use the rat medial meniscus transection (MMT) model to discover stage and tissue-specific tran-scriptomic changes.Design: Sham or MMT surgeries were performed in mature rats. Cartilage, menisci and synovium were scored for histopathological changes at 2, 4 and 6 weeks post-surgery and processed for RNA-sequencing. Differentially expressed genes (DEG) were used to identify pathways and mechanisms. Published tran-scriptomic datasets from animal models and human OA were used to confirm and extend present findings.Results: The total number of DEGs was already high at 2 weeks (723 in meniscus), followed by cartilage (259) and synovium (42) and declined to varying degrees in meniscus and synovium but increased in cartilage at 6 weeks. The most upregulated genes included tenascins. The 'response to mechanical stimulus' and extracellular matrix-related pathways were enriched in both cartilage and meniscus. Pathways that were enriched in synovium at 4 weeks indicate processes related to synovial hyperplasia and fibrosis. Synovium also showed upregulation of IL-11 and several MMPs. The mechanical stimulus pathway included upregulation of the mechanoreceptors PIEZO1, PIEZO2 and TRPV4 and nerve growth factor. Analysis of data from prior RNA-sequencing studies of animal models and human OA support these findings.Conclusion: These results indicate several shared pathways that are affected during OA in cartilage and meniscus and support the role of mechanotransduction and other pathways in OA pathogenesis.(c) 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：199 / 212

页数：14