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      Cell cycle-related lncRNAs and mRNAs in osteoarthritis chondrocytes in a Northwest Chinese Han Population

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          Abstract

          Supplemental Digital Content is available in the text

          Abstract

          Background:

          A group of differentially expressed long non-coding RNAs (lncRNAs) have been shown to play key roles in osteoarthritis (OA), although they represented only a small proportion of lncRNAs that may be biologically and physiologically relevant. Since our knowledge of regulatory functions of non-coding RNAs is still limited, it is important to gain better understanding of their relation to the pathogenesis of OA.

          Methods:

          We performed mRNA and lncRNA microarray analysis to detect differentially expressed RNAs in chondrocytes from three OA patients compared with four healthy controls. Then, enrichment analysis of the differentially expressed mRNAs was carried out to define disease molecular networks, pathways and gene ontology (GO) function. Furthermore, target gene prediction based on the co-expression network was performed to reveal the potential relationships between lncRNAs and mRNAs, contributing an exploration of a role of lncRNAs in OA mechanism. Quantitative RT-PCR analyses were used to demonstrate the reliability of the experimental results.

          Findings:

          Altogether 990 lncRNAs (666 up-regulated and 324 down-regulated) and 546 mRNAs (419 up-regulated and 127 down-regulated) were differentially expressed in OA samples compared with the normal ones. The enrichment analysis revealed a set of genes involved in cell cycle. In total, 854 pairs of mRNA and lncRNA were highly linked, and further target prediction appointed 12 genes specifically for their corresponding lncRNAs. The lncRNAs lncRNA-CTD-2184D3.4, ENST00000564198.1, and ENST00000520562.1 were predicted to regulate SPC24, GALM, and ZNF345 mRNA expressions in OA.

          Interpretation:

          This study uncovered several novel genes potentially important in pathogenesis of OA, and forecast the potential function of lnc-CTD-2184D3.4, especially for the cell cycle in the chondrocytes. These findings may promote additional aspects in studies of OA.

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          Most cited references27

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          Identification of genes periodically expressed in the human cell cycle and their expression in tumors.

          The genome-wide program of gene expression during the cell division cycle in a human cancer cell line (HeLa) was characterized using cDNA microarrays. Transcripts of >850 genes showed periodic variation during the cell cycle. Hierarchical clustering of the expression patterns revealed coexpressed groups of previously well-characterized genes involved in essential cell cycle processes such as DNA replication, chromosome segregation, and cell adhesion along with genes of uncharacterized function. Most of the genes whose expression had previously been reported to correlate with the proliferative state of tumors were found herein also to be periodically expressed during the HeLa cell cycle. However, some of the genes periodically expressed in the HeLa cell cycle do not have a consistent correlation with tumor proliferation. Cell cycle-regulated transcripts of genes involved in fundamental processes such as DNA replication and chromosome segregation seem to be more highly expressed in proliferative tumors simply because they contain more cycling cells. The data in this report provide a comprehensive catalog of cell cycle regulated genes that can serve as a starting point for functional discovery. The full dataset is available at http://genome-www.stanford.edu/Human-CellCycle/HeLa/.
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            A twist code determines the onset of osteoblast differentiation.

            Runx2 is necessary and sufficient for osteoblast differentiation, yet its expression precedes the appearance of osteoblasts by 4 days. Here we show that Twist proteins transiently inhibit Runx2 function during skeletogenesis. Twist-1 and -2 are expressed in Runx2-expressing cells throughout the skeleton early during development, and osteoblast-specific gene expression occurs only after their expression decreases. Double heterozygotes for Twist-1 and Runx2 deletion have none of the skull abnormalities observed in Runx2(+/-) mice, a Twist-2 null background rescues the clavicle phenotype of Runx2(+/-) mice, and Twist-1 or -2 deficiency leads to premature osteoblast differentiation. Furthermore, Twist-1 overexpression inhibits osteoblast differentiation without affecting Runx2 expression. Twist proteins' antiosteogenic function is mediated by a novel domain, the Twist box, which interacts with the Runx2 DNA binding domain to inhibit its function. In vivo mutagenesis confirms the antiosteogenic function of the Twist box. Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation.
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              Is Open Access

              Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

              There is an important need to evaluate therapeutic approaches for osteoarthritis (OA) in terms of cost-effectiveness as well as efficacy.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                12 June 2020
                12 June 2020
                : 99
                : 24
                : e19905
                Affiliations
                [a ]School of Public Health, Health Science Center of Xi’an Jiaotong University
                [b ]Collaborative Innovation Center of Endemic Diseases and Health Promotion for Silk Road Region of Shaanxi Province
                [c ]Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi’an, P.R. China
                [d ]Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden.
                Author notes
                []Correspondence: Xiong Guo, School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of People's Republic of China, Xi’an Jiaotong University, No.76 Yan Ta West Road, Xi’an, Shaanxi 710061, P.R. China (e-mail: guox@ 123456xjtu.edu.cn ).
                Article
                MD-D-19-08257 19905
                10.1097/MD.0000000000019905
                7302618
                32541446
                3b353e5e-d016-4663-975d-319800b3e0d4
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 29 October 2019
                : 25 February 2020
                : 16 March 2020
                Categories
                6900
                Research Article
                Clinical Trial/Experimental Study
                Custom metadata
                TRUE

                cell-cycle,differential expression,long non-coding rnas,messenger rnas,osteoarthritis

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