| 1. |
- Liu, Huan, et al.
(författare)
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The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway
- 2022
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:1, s. 279-293
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing.METHODS: HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donors via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by real-time quantitative reverse transcription PCR (RT-qPCR).RESULTS: KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin, PPAR signaling pathway and cell adhesion molecules (CAMs) pathways were identified to be significantly altered in KBD.CONCLUSION: Differentiated chondrocytes deriving from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.
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| 2. |
- Wu, Cuiyan, et al.
(författare)
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Long noncoding RNA expression profile reveals lncRNAs signature associated with extracellular matrix degradation in kashin-beck disease
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.
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| 3. |
- Yang, Lei, et al.
(författare)
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Gene expression profiles and molecular mechanism of cultured human chondrocytes' exposure to T-2 toxin and deoxynivalenol
- 2017
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Ingår i: Toxicon. - Amsterdam : Elsevier. - 0041-0101 .- 1879-3150. ; 140, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- T-2 toxin and deoxynivalenol (DON) are secondary metabolites produced by Fusarium fungi and are commonly found on food and feed. Although T-2 toxin and DON have been suggested as the etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, little is known about the mechanism when human chondrocytes are exposed to T-2 toxin and DON. The purpose of this study is to identify the gene expression differences and underlying molecular changes modulated by T-2 toxin and DON in vitro in human chondrocytes. After the experiments of cell viability, the gene expression profiles were analyzed in cells that were treated with 0.01 μg/ml T-2 toxin and 1.0 μg/ml DON for 72 h by Affymetrix Human Gene Chip. The array results showed that 882 and 2118 genes were differentially expressed for T-2 toxin and DON exposure, respectively. Enrichment analysis revealed that diverse cellular processes including DNA damage, cell cycle regulation and metabolism of extracellular matrix were affected when human chondrocytes were exposed to T-2 toxin and DON. These results demonstrate the gene expression differences and molecular mechanism of cultured human chondrocytes exposure to T-2 toxin and DON, and provide a new insight into future research in the etiology of KBD.
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