Int J Med Sci 2019; 16(8):1057-1071. doi:10.7150/ijms.35611

Research Paper

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Yi-Jen Chen1,2, Wei-An Chang1,3, Ling-Yu Wu1, Ching-Fen Huang1,2, Chia-Hsin Chen2,4,5✉, Po-Lin Kuo1,6✉

1. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2. Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3. Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4. Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6. Center for Cancer Research, Kaohsiung Medical University

Abstract

Synovitis in osteoarthritis (OA) the consequence of low grade inflammatory process caused by cartilage breakdown products that stimulated the production of pro-inflammatory mediators by fibroblast-like synoviocytes (FLS). FLS participate in joint homeostasis and low grade inflammation in the joint microenvironment triggers FLS transformation. In the current study, we aimed to identify differentially expressed genes and potential miRNA regulations in human OA FLS through deep sequencing and bioinformatics approaches. The 245 differentially expressed genes in OA FLS were identified, and pathway analysis using various bioinformatics databases indicated their enrichment in functions related to altered extracellular matrix organization, cell adhesion and cellular movement. Moreover, among the 14 dysregulated genes with potential miRNA regulations identified, src kinase associated phosphoprotein 2 (SKAP2), adaptor related protein complex 1 sigma 2 subunit (AP1S2), PHD finger protein 21A (PHF21A), lipoma preferred partner (LPP), and transcription factor AP-2 alpha (TFAP2A) showed similar expression patterns in OA FLS and OA synovial tissue datasets in Gene Expression Omnibus database. Ingenuity Pathway Analysis identified the dysregulated LPP participated in cell migration and cell spreading of OA FLS, which was potentially regulated by miR-141-3p. The current findings suggested new perspectives into understanding the novel molecular signatures of FLS involved in the pathogenesis of OA, which may be potential therapeutic targets.

Keywords: osteoarthritis, synovitis, fibroblast-like synoviocytes, next-generation sequencing, messenger RNA, microRNA, bioinformatics

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How to cite this article:
Chen YJ, Chang WA, Wu LY, Huang CF, Chen CH, Kuo PL. Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches. Int J Med Sci 2019; 16(8):1057-1071. doi:10.7150/ijms.35611. Available from http://www.medsci.org/v16p1057.htm