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J Clin Med. 2018 Dec 10;7(12). pii: E535. doi: 10.3390/jcm7120535.

Systematic Analysis of Transcriptomic Profile of Chondrocytes in Osteoarthritic Knee Using Next-Generation Sequencing and Bioinformatics.

Chen YJ1,2, Chang WA3,4, Wu LY5, Hsu YL6, Chen CH7,8,9, Kuo PL10,11.

Author information

1
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chernkmu@gmail.com.
2
Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chernkmu@gmail.com.
3
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. 960215kmuh@gmail.com.
4
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. 960215kmuh@gmail.com.
5
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. esther906@gmail.com.
6
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. hsuyl326@gmail.com.
7
Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chchen@kmu.edu.tw.
8
Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chchen@kmu.edu.tw.
9
Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chchen@kmu.edu.tw.
10
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. kuopolin@seed.net.tw.
11
Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. kuopolin@seed.net.tw.

Abstract

The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 (SMAD3) and Wnt family member 5A (WNT5A) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA. Additionally, 26 dysregulated genes with potential miRNA⁻mRNA interactions were identified in OA knee chondrocytes. Myristoylated alanine rich protein kinase C substrate (MARCKS), epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in Gene Expression Omnibus database. The Ingenuity Pathway Analysis identified MARCKS to be associated with the outgrowth of neurite, and novel miRNA regulations were proposed to play critical roles in the pathogenesis of the altered OA knee joint microenvironment. The current findings suggest new perspectives in studying novel genes potentially contributing to arthritic joint pain in knee OA, which may assist in finding new targets for OA treatment.

KEYWORDS:

bioinformatics; cartilage damage; chondrocytes; joint pain; knee osteoarthritis; messenger RNA; microRNA; next-generation sequencing

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