Transcriptome comparison of meniscus from patients with and without osteoarthritis

被引:60
作者
Brophy, R. H. [1 ]
Zhang, B. [3 ]
Cai, L. [1 ]
Wright, R. W. [1 ]
Sandell, L. J. [1 ,2 ,4 ]
Rai, M. F. [1 ,2 ]
机构
[1] Washington Univ, Barnes Jewish Hosp, Dept Orthopaed Surg, Musculoskeletal Res Ctr,Sch Med, MS 8233,660 South Euclid Ave, St Louis, MO 63110 USA
[2] Washington Univ, Barnes Jewish Hosp, Dept Cell Biol & Physiol, Sch Med, 660 South Euclid Ave, St Louis, MO 63110 USA
[3] Washington Univ, Barnes Jewish Hosp, Dept Dev Biol, Ctr Regenerat Med,Sch Med, 660 South Euclid Ave, St Louis, MO 63110 USA
[4] Washington Univ, Dept Biomed Engn, Sch Engn & Appl Sci, 1 Brookings Dr, St Louis, MO 63130 USA
基金
美国国家卫生研究院;
关键词
Meniscus tear; Partial meniscectomy; Microarrays; lncRNAs; Epigenetics; Osteoarthritis; ANTERIOR CRUCIATE LIGAMENT; WIDE GENE-EXPRESSION; LONG NONCODING RNAS; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE; MATRIX DEGRADATION; PERIOSTIN; ANGIOGENESIS; REVEALS;
D O I
10.1016/j.joca.2017.12.004
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: To assess the impact of osteoarthritis (OA) on the meniscus by comparing transcripts and biological processes in the meniscus between patients with and without OA. Design: RNA microarrays were used to identify transcripts differentially expressed (DE) in meniscus obtained from 12 OA and 12 non-OA patients. The non-OA specimens were obtained at the time of arthroscopic partial meniscectomy. Real-time PCR was performed on selected transcripts. Biological processes and gene-networking was examined computationally. Transcriptome signatures were mapped with 37 OA-related transcripts to evaluate how meniscus gene expression relates to that of OA cartilage. Results: We identified 168 transcripts significantly DE between OA (75 elevated, 93 repressed) and nonOA samples (>= 1.5-fold). Among these, CSN1S1, COL10A1, WIF1, and SPARCL1 were the most prominent transcripts elevated in OA meniscus, POSTN and VEGFA were most highly repressed in OA meniscus. Transcripts elevated in OA meniscus represented response to external stimuli, cell migration and cell localization while those repressed in OA meniscus represented histone deacetylase activity (related to epigenetics) and skeletal development. Numerous long non-coding RNAs (lncRNAs) were DE between the two groups. When segregated by OA-related transcripts, two distinct clustering patterns appeared: OA meniscus appeared to be more inflammatory while non-OA meniscus exhibited a "repair" phenotype. Conclusions: Numerous transcripts with potential relevance to the pathogenesis of OA are DE in OA and non-OA meniscus. These data suggest an involvement of epigenetically regulated histone deacetylation in meniscus tears as well as expression of lncRNAs. Patient clustering based on transcripts related to OA in articular cartilage confirmed distinct phenotypes between injured (non-OA) and OA meniscus. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
引用
收藏
页码:422 / 432
页数:11
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