Int J Mol Sci. 2017 Nov 11;18(11). pii: E2396. doi: 10.3390/ijms18112396.

Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches.

Chen YJ^1,^2,³, Chang WA^4,⁵, Hsu YL⁶, Chen CH^7,^8,^9,¹⁰, Kuo PL^11,¹².

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: Department of Physical Medicine and Rehabilitation, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan. chernkmu@gmail.com.
4: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. 960215kmuh@gmail.com.
5: Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. 960215kmuh@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, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan. chchen@kmu.edu.tw.
9: Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chchen@kmu.edu.tw.
10: Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chchen@kmu.edu.tw.
11: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. kuopolin@seed.net.tw.
12: Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. kuopolin@seed.net.tw.

Abstract

The role of osteoblasts in peri-articular bone loss and bone erosion in rheumatoid arthritis (RA) has gained much attention, and microRNAs are hypothesized to play critical roles in the regulation of osteoblast function in RA. The aim of this study is to explore novel microRNAs differentially expressed in RA osteoblasts and to identify genes potentially involved in the dysregulated bone homeostasis in RA. RNAs were extracted from cultured normal and RA osteoblasts for sequencing. Using the next generation sequencing and bioinformatics approaches, we identified 35 differentially expressed microRNAs and 13 differentially expressed genes with potential microRNA-mRNA interactions in RA osteoblasts. The 13 candidate genes were involved mainly in cell-matrix adhesion, as classified by the Gene Ontology. Two genes of interest identified from RA osteoblasts, A-kinase anchoring protein 12 (AKAP12) and leucin rich repeat containing 15 (LRRC15), were found to express more consistently in the related RA synovial tissue arrays in the Gene Expression Omnibus database, with the predicted interactions with miR-183-5p and miR-146a-5p, respectively. The Ingenuity Pathway Analysis identified AKAP12 as one of the genes involved in protein kinase A signaling and the function of chemotaxis, interconnecting with molecules related to neovascularization. The findings indicate new candidate genes as the potential indicators in evaluating therapies targeting chemotaxis and neovascularization to control joint destruction in RA.