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      Transcriptome analyses identify key genes and potential mechanisms in a rat model of osteoarthritis

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          Abstract

          Background

          Osteoarthritis (OA) is one of the most common degenerative diseases of the joints worldwide, but still the pathogenesis of OA is largely unknown. The purpose of our study is to clarify key candidate genes and relevant signaling pathways in a surgical-induced OA rat model.

          Methods

          The microarray raw data of GSE8077 was downloaded from GEO datasets. GeoDiver were employed to screen differentially-expressed genes (DEGs). Enrichment analyses of DEGs were performed using Metascape. Construction of protein–protein interaction (PPI) network and identification of key genes were conducted using STRING, Cytoscape v3.6.0, and Centiscape2.2. Furthermore, miRDB and Cytoscape v3.6.0 were used for visualization of miRNA-mRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for predicted miRNAs was undertaken using DIANA-miRPath v3.0.

          Results

          Several DEGs (188 in comparison between OA and sham-operated group and 160 in comparison between OA and contralateral group) were identified. DEGs mainly enriched in vasculature development, regulation of cell migration, response to growth factor (Gene ontology), and ECM-receptor interaction (KEGG). Two comparison cohorts shared 79 intersection genes, and of these, Ccl2, Col4a1, Col1a1, Aldh1a3, and Itga8 were defined as the hub genes. Predicted miRNAs of seven DEGs from sub-networks mainly enriched in MAPK signaling pathway.

          Conclusion

          The current study shows that some key genes and pathways, such as Ccl2, Col4a1, Col1a1, Aldh1a3, Itga8, ECM-receptor interaction, and MAPK signaling pathway may be associated with OA progression and act as potential biomarkers and therapeutic targets for OA.

          Electronic supplementary material

          The online version of this article (10.1186/s13018-018-1019-3) contains supplementary material, which is available to authorized users.

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          Most cited references38

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          Integration of biological networks and gene expression data using Cytoscape.

          Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.
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            miRDB: an online resource for microRNA target prediction and functional annotations

            MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in many physiological and disease processes. One major challenge in miRNA studies is the identification of genes regulated by miRNAs. To this end, we have developed an online resource, miRDB (http://mirdb.org), for miRNA target prediction and functional annotations. Here, we describe recently updated features of miRDB, including 2.1 million predicted gene targets regulated by 6709 miRNAs. In addition to presenting precompiled prediction data, a new feature is the web server interface that allows submission of user-provided sequences for miRNA target prediction. In this way, users have the flexibility to study any custom miRNAs or target genes of interest. Another major update of miRDB is related to functional miRNA annotations. Although thousands of miRNAs have been identified, many of the reported miRNAs are not likely to play active functional roles or may even have been falsely identified as miRNAs from high-throughput studies. To address this issue, we have performed combined computational analyses and literature mining, and identified 568 and 452 functional miRNAs in humans and mice, respectively. These miRNAs, as well as associated functional annotations, are presented in the FuncMir Collection in miRDB.
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              2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis

              Regular physical activity (PA) is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. We evaluated if the public health recommendations for PA are applicable for people with inflammatory arthritis (iA; Rheumatoid Arthritis and Spondyloarthritis) and osteoarthritis (hip/knee OA) in order to develop evidence-based recommendations for advice and guidance on PA in clinical practice. The EULAR standardised operating procedures for the development of recommendations were followed. A task force (TF) (including rheumatologists, other medical specialists and physicians, health professionals, patient-representatives, methodologists) from 16 countries met twice. In the first TF meeting, 13 research questions to support a systematic literature review (SLR) were identified and defined. In the second meeting, the SLR evidence was presented and discussed before the recommendations, research agenda and education agenda were formulated. The TF developed and agreed on four overarching principles and 10 recommendations for PA in people with iA and OA. The mean level of agreement between the TF members ranged between 9.8 and 8.8. Given the evidence for its effectiveness, feasibility and safety, PA is advocated as integral part of standard care throughout the course of these diseases. Finally, the TF agreed on related research and education agendas. Evidence and expert opinion inform these recommendations to provide guidance in the development, conduct and evaluation of PA-interventions and promotion in people with iA and OA. It is advised that these recommendations should be implemented considering individual needs and national health systems.
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                Author and article information

                Contributors
                86-756-2587423 , lhzdoctor182@163.com
                86-756-2528818 , johnniehuading@163.com
                Journal
                J Orthop Surg Res
                J Orthop Surg Res
                Journal of Orthopaedic Surgery and Research
                BioMed Central (London )
                1749-799X
                14 December 2018
                14 December 2018
                2018
                : 13
                : 319
                Affiliations
                [1 ]GRID grid.452859.7, Department of Orthopaedics, , The Fifth Affiliated Hospital of Sun Yat-Sen University, ; Zhuhai, 519000 Guangdong China
                [2 ]GRID grid.452859.7, Guangdong Provincial Engineering Research Center of Molecular Imaging, , The Fifth Affiliated Hospital of Sun Yat-Sen University, ; Zhuhai, 519000 Guangdong Province China
                Article
                1019
                10.1186/s13018-018-1019-3
                6295024
                30551734
                ee7b4936-1f9c-4899-a841-2919eac56d57
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 April 2018
                : 26 November 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Surgery
                osteoarthritis,differentially expressed genes,animal model,bioinformatics analysis
                Surgery
                osteoarthritis, differentially expressed genes, animal model, bioinformatics analysis

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