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      Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head

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          Abstract

          Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction and target genes were predicted by bioinformatics databases. Target genes related with angiogenesis and osteogenesis were quantified by RT-qPCR in necrotic bone tissue. Our findings demonstrated that multiple miRNAs were evaluated to be differentially expressed with high dignostic values. MiR-127-3p, miR-628-3p, and miR-1 were downregulated, whereas miR-885-5p, miR-483-3p, and miR-483-5p were upregulated in serum and bone samples from the AIONFH patients compared to those from the normal control individuals ( p < 0.01). The predicted target genes of the indicated miRNAs quantified by qRT-PCR, including IGF2, PDGFA, RUNX2, PTEN, and VEGF, were presumed to be altered in necrotic bone tissue of AIONFH patients. The presence of five altered miRNAs in AIONFH patients may serve as non-invasive biomarkers and potential therapeutic targets for the early diagnosis of AIONFH.

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          Most cited references34

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          Nontraumatic osteonecrosis of the femoral head: ten years later.

          The etiology of osteonecrosis of the hip may have a genetic basis. The interaction between certain risk factors and a genetic predisposition may determine whether this disease will develop in a particular individual. The rationale for use of joint-sparing procedures in the treatment of this disease is based on radiographic measurements and findings with other imaging modalities. Early diagnosis and intervention prior to collapse of the femoral head is key to a successful outcome of joint-preserving procedures. The results of joint-preserving procedures are less satisfactory than the results of total hip arthroplasty for femoral heads that have already collapsed. New pharmacological measures as well as the use of growth and differentiation factors for the prevention and treatment of this disease may eventually alter our treatment approach, but it is necessary to await results of clinical research with long-term follow-up of these patients.
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            The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis

            Insulin-like growth factor 2 (IGF2) is frequently overexpressed in pediatric cancers. In a miRNA screen of primary Wilms' tumors, Haber and colleagues identify specific overexpression of miR-483-5p, which is embedded in the IGF2 gene. Interestingly, the IGF2 mRNA itself is transcriptionally up-regulated by miR-483-5p. A nuclear pool of miR-483-5p binds the IGF2 mRNA, enhancing the association of RNA helicase and promoting IGF2 transcription. This unexpected nuclear function for a miRNA points to the complexity of mechanisms regulating IGF2 expression, implicated in both normal development and cancer.
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              Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head

              Background and aim The biological functions of non-coding RNAs (ncRNAs) have been widely identified in many human diseases. In the present study, the relationship between long non-coding RNA HOTAIR and microRNA-17-5p (miR-17-5p) and their roles in osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head (ONFH) were investigated. Methods The expression levels of HOTAIR and miR-17-5p in the mesenchymal stem cells (MSCs) derived from patients with non-traumatic ONFH and osteoarthritis (OA) were examined by real-time PCR. BMP-2 induced human MSCs from bone marrow (hMSC-BM) were used for osteogenic differentiation. Results It was observed that the expression level of miR-17-5p was lower and the level of HOTAIR was higher in samples of non-traumatic ONFH compared with OA. HOTAIR downregulation induced by si-HOTAIR led to the increase of miR-17-5p expression and the decrease of miR-17-5p target gene SMAD7 expression. The values of osteogenic differentiation markers, including RUNX2 and COL1A1 mRNA expression and ALP activity, were also elevated by si-HOTAIR. However, the increase of these values was canceled by miR-17-5p inhibitor or SMAD7 upregulation. Conclusion HOTAIR played a role in regulating osteogenic differentiation and proliferation through modulating miR-17-5p and its target gene SMAD7 in non-traumatic ONFH.
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                Author and article information

                Contributors
                weiqshi@126.com
                gdstjeeson@foxmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 December 2019
                12 December 2019
                2019
                : 9
                : 18926
                Affiliations
                [1 ]GRID grid.17089.37, Devision of Orthopeadic Surgery, , the University of Alberta, ; Edmonton, Alberta T6G 2R3 Canada
                [2 ]ISNI 0000 0000 8848 7685, GRID grid.411866.c, The National Key Discipline and the Orthopedic Laboratory, , Guangzhou University of Chinese Medicine, ; Guangzhou, Guangdong 510405 P.R. China
                [3 ]ISNI 0000 0004 1764 3838, GRID grid.79703.3a, School of Medicine, , South China University of Technology, ; Guangzhou, Guangdong 510641 P.R. China
                [4 ]GRID grid.412595.e, Department of Orthopedic, , the First Affiliated Hospital of Guangzhou University of Chinese Medicine, ; Guangzhou, Guangdong 510405 P.R. China
                [5 ]GRID grid.412595.e, Hip Preserving Ward, No. 3 Orthopaedic Region, , the First Affiliated Hospital of Guangzhou University of Chinese Medicine, ; Guangzhou, Guangdong 510405 P.R. China
                [6 ]ISNI 0000 0004 1936 7910, GRID grid.1012.2, School of Biomedical Sciences, , the University of Western Australia, ; Perth, Western Australia 6009 Australia
                [7 ]ISNI 0000 0004 1758 4014, GRID grid.477976.c, Department of Endocrinology, , The First Affiliated Hospital of Guangdong Pharmaceutical University, ; Guangzhou, Guangdong 510080 P.R. China
                Author information
                http://orcid.org/0000-0003-4832-164X
                Article
                55188
                10.1038/s41598-019-55188-6
                6908598
                31831773
                815d2bb9-865c-4d46-a99e-b15e8cd2ebd6
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 April 2019
                : 22 November 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81473697
                Award ID: 81573996
                Award Recipient :
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                © The Author(s) 2019

                Uncategorized
                metabolic disorders,genetics research
                Uncategorized
                metabolic disorders, genetics research

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