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      lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes

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          Abstract

          Osteoarthritis (OA) is the most common motor system disease in aging people, characterized by matrix degradation, chondrocyte death, and osteophyte formation. OA etiology is unclear, but long noncoding RNAs (lncRNAs) that participate in numerous pathological and physiological processes may be key regulators in the onset and development of OA. Because profiling of lncRNAs and their biological function in OA is not understood, we measured lncRNA and mRNA expression profiles using high-throughput microarray to study human knee OA. We identified 2,042 lncRNAs and 2,011 mRNAs that were significantly differentially expressed in OA compared to non-OA tissue (>2.0- or < − 2.0-fold change; p < 0.5), including 1,137 lncRNAs that were upregulated and 905 lncRNAs that were downregulated. Also, 1,386 mRNA were upregulated and 625 mRNAs were downregulated. QPCR was used to validate chip results. Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes was used to study the biological function enrichment of differentially expressed mRNA. Additionally, coding-non-coding gene co-expression (CNC) network construction was performed to explore the relevance of dysregulated lncRNAs and mRNAs. Finally, the gain/loss of function experiments of lnc-SAMD14-4 was implemented in IL-1 β-treated human chondrocytes. In general, this study provides a preliminary database for further exploring lncRNA-related mechnisms in OA.

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          Most cited references34

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          A gene-coexpression network for global discovery of conserved genetic modules.

          To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are functionally related. Many of these relationships provide strong evidence for the involvement of new genes in core biological functions such as the cell cycle, secretion, and protein expression. We experimentally confirmed the predictions implied by some of these links and identified cell proliferation functions for several genes. By assembling these links into a gene-coexpression network, we found several components that were animal-specific as well as interrelationships between newly evolved and ancient modules.
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            PI3K/Akt and apoptosis: size matters.

            Recent research has examined Akt and Akt-related serine-threonine kinases in signaling cascades that regulate cell survival and are important in the pathogenesis of degenerative diseases and in cancer. We seek to recapitulate the research that has helped to define the current understanding of the role of the Akt pathway under normal and pathologic conditions, also in view of genetic models of Akt function. In particular, we will evaluate the mechanisms of Akt regulation and the role of Akt substrates in Akt-dependent biologic responses in the decisions of cell death and cell survival. Here, we hope to establish the mechanisms of apoptosis suppression by Akt kinase as a framework for a more general understanding of growth factor-dependent regulation of cell survival.
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              Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis.

              Autophagy is a process for turnover of intracellular organelles and molecules that protects cells during stress responses. We undertook this study to evaluate the potential roles of Unc-51-like kinase 1 (ULK1), an inducer of autophagy, Beclin1, a regulator of autophagy, and microtubule-associated protein 1 light chain 3 (LC3), which executes autophagy, in the development of osteoarthritis (OA) and in cartilage cell death. Expression of ULK1, Beclin1, and LC3 was analyzed in normal and OA human articular cartilage and in knee joints of mice with aging-related and surgically induced OA, using immunohistochemistry and Western blotting. Poly(ADP-ribose) polymerase (PARP) p85 expression was used to determine the correlation between cell death and autophagy. ULK1, Beclin1, and LC3 were constitutively expressed in normal human articular cartilage. ULK1, Beclin1, and LC3 protein expression was reduced in OA chondrocytes and cartilage, but these 3 proteins were strongly expressed in the OA cell clusters. In mouse knee joints, loss of glycosaminoglycans (GAGs) was observed at ages 9 months and 12 months and in the surgical OA model, 8 weeks after knee destabilization. Expression of ULK1, Beclin1, and LC3 decreased together with GAG loss, while PARP p85 expression was increased. Autophagy may be a protective or homeostatic mechanism in normal cartilage. In contrast, human OA and aging-related and surgically induced OA in mice are associated with a reduction and loss of ULK1, Beclin1, and LC3 expression and a related increase in apoptosis. These results suggest that compromised autophagy represents a novel mechanism in the development of OA.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                2 September 2019
                2019
                : 7
                : e7491
                Affiliations
                [1 ]Department of Orthopedics, The NO.921 Hospital of the People’s Liberation Army Joint Support Force, The Second Affiliated Hospital of Hunan Normal University , Changsha, Hunan, China
                [2 ]Department of Pharmaceutical Sciences, Hunan Normal University , changsha, Hunan, China
                [3 ]Department of Orthopedics, Changsha central hospital , Changsha, Hunan, China
                [4 ]Department of Traumatology, Shanxi Fenyang Hospital, The Fenyang Hospital of Shanxi Medical University , Fenyang, Shanxi, China
                [5 ]Department of Orthopedics, The Second Xiangya Hospital of Central South University , Changsha, Hunan, China
                [6 ]Department of Orthopedics, People’s Hospital of Xiangxi Autonomous Prefecture , Jishou, Hunan, China
                Article
                7491
                10.7717/peerj.7491
                6727836
                31534838
                8b282ee1-82c8-4148-a61b-3394feb59938
                ©2019 Zhang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 28 May 2018
                : 16 July 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: #81201432
                Award ID: 81371997
                Funded by: Army Medical Research Subject of the 12th Five-Year-Plan fund
                Award ID: #CWS11J275
                Funded by: Scientific Research Fund of Hunan Provincial Education Department
                Award ID: #15B140
                Funded by: Hunan Province Health and Life Committee Scientific Research Project
                Award ID: #B2016148
                Funded by: Military Medical Science and Technology Youth Training Program
                Award ID: #2018JJ6033
                Funded by: Hunan Provincial Innovation Foundation for Postgraduates
                Award ID: #CX2015B185
                The study was supported by the National Natural Science Foundation of China (#81201432, 81371997), the Army Medical Research Subject of the 12th Five-Year-Plan fund (#CWS11J275), the Scientific Research Fund of Hunan Provincial Education Department (#15B140), the Hunan Province Health and Life Committee Scientific Research Project (#B2016148), the Military Medical Science and Technology Youth Training Program (#2018JJ6033), and the Hunan Provincial Innovation Foundation for Postgraduates (#CX2015B185). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Genetics
                Genomics
                Orthopedics
                Ethical Issues

                long-coding ribonucleicacids,microarray,expression profile,osteoarthritis

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