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

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 expres...

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Main Authors: Yi-Jen Chen, Wei-An Chang, Ya-Ling Hsu, Chia-Hsin Chen, Po-Lin Kuo
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/18/11/2396
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spelling doaj-fcaa7468ba3b424c85a6e02b615ef0ed2020-11-24T22:33:52ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-11-011811239610.3390/ijms18112396ijms18112396Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic ApproachesYi-Jen Chen0Wei-An Chang1Ya-Ling Hsu2Chia-Hsin Chen3Po-Lin Kuo4Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanThe 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.https://www.mdpi.com/1422-0067/18/11/2396rheumatoid arthritisbone erosionosteoblastsnext-generation sequencingbioinformaticsmicroRNAmessenger RNA
collection DOAJ
language English
format Article
sources DOAJ
author Yi-Jen Chen
Wei-An Chang
Ya-Ling Hsu
Chia-Hsin Chen
Po-Lin Kuo
spellingShingle Yi-Jen Chen
Wei-An Chang
Ya-Ling Hsu
Chia-Hsin Chen
Po-Lin Kuo
Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
International Journal of Molecular Sciences
rheumatoid arthritis
bone erosion
osteoblasts
next-generation sequencing
bioinformatics
microRNA
messenger RNA
author_facet Yi-Jen Chen
Wei-An Chang
Ya-Ling Hsu
Chia-Hsin Chen
Po-Lin Kuo
author_sort Yi-Jen Chen
title Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
title_short Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
title_full Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
title_fullStr Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
title_full_unstemmed Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches
title_sort deduction of novel genes potentially involved in osteoblasts of rheumatoid arthritis using next-generation sequencing and bioinformatic approaches
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2017-11-01
description 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.
topic rheumatoid arthritis
bone erosion
osteoblasts
next-generation sequencing
bioinformatics
microRNA
messenger RNA
url https://www.mdpi.com/1422-0067/18/11/2396
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