4.6 Article

Transcriptome comparison of meniscus from patients with and without osteoarthritis

Journal

OSTEOARTHRITIS AND CARTILAGE
Volume 26, Issue 3, Pages 422-432

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2017.12.004

Keywords

Meniscus tear; Partial meniscectomy; Microarrays; lncRNAs; Epigenetics; Osteoarthritis

Funding

  1. AOSSM/Sanofi Osteoarthritis Research Grant [OA2013-1]
  2. National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH) [R01AR063757, P30 AR057235, R00 AR064837]

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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.

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