| 1. |
- Guo, Xiong, et al.
(author)
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Kashin-Beck Disease (KBD)
- 2017
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In: Endemic disease in China. - Beijing : People's Medical Publishing House. - 9787117247139 ; , s. 150-211
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Book chapter (peer-reviewed)
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| 2. |
- Liu, Huan, et al.
(author)
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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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In: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:1, s. 279-293
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Journal article (peer-reviewed)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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| 3. |
- Liu, Huan, et al.
(author)
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The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions
- 2017
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In: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 25:5, s. 616-624
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Research review (peer-reviewed)abstract
- The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA.
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| 4. |
- Wang, Sen, et al.
(author)
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Roles of glycoprotein glycosylation in the pathogenesis of an endemic osteoarthritis, Kashin–Beck disease, and effectiveness evaluation of sodium hyaluronate treatment
- 2020
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In: Turkish Journal of Medical Sciences. - : TÜBİTAK (the Scientific and Technological Research Council of Turkey). - 1300-0144 .- 1303-6165. ; 50:4, s. 1028-1037
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Journal article (peer-reviewed)abstract
- Background/aim: We aimed to explore the roles of glycoprotein glycosylation in the pathogenesis of Kashin–Beck disease (KBD), and evaluated the effectiveness of sodium hyaluronate treatment.Materials and methods: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups.Results: In saliva lectin microarray, bindings to Sophora japonica agglutinin (SJA), Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I), Euonymus europaeus lectin (EEL), Maackia amurensis lectin II (MAL-II), Sambucus nigra lectin (SNA), Hippeastrum hybrid lectin (HHL), and Aleuria aurantia lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels of HHL, MAL-II, and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and control groups. In serum lectin microarray, HHL and peanut agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris agglutinin (E+L) (PHA- E+L), and Psophocarpus tetragonolobus lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and control groups. Hyaluronate treatment appeared to normalize SNA, AAL, and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I, and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between the groups in SNA and Jacalin, in particular for GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA, and AAL levels returned to normal levels after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL, and Jacalin in saliva, and HHL, PNA, PHA-E+L, and AAL in serum.Conclusion: HHL in saliva and serum may be a valuable diagnostic biomarker of KBD, and it may be used as follow-up for the hyaluronate treatment.
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| 5. |
- Wang, Sen, et al.
(author)
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The importance of Se-related genes in the chondrocyte of Kashin-Beck disease revealed by whole genomic microarray and network analysis
- 2019
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In: Biological Trace Element Research. - : Springer. - 0163-4984 .- 1559-0720. ; 187:2, s. 367-375
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Journal article (peer-reviewed)abstract
- Kashin-Beck disease (KBD) is an endemic, chronic, and degenerative osteoarthropathy. Selenium (Se) deficiency plays important role in the pathogenesis of KBD. We aimed to screen Se-related gene from chondrocytes of patients with KBD. Whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. qRT-PCR was used to confirm the microarray results. Comparative Toxicogenomics Database (CTD) was used to screen Se-related genes from differentially expressed genes. Gene Ontology (GO) classifications and network analysis of Se-related genes were constituted by STRING online system. Three hundred ninety-nine differentially expressed genes were obtained from microarray. Among them, 54 Se-related genes were identified by CTD. The qRT-PCR validation showed that four genes expressed similarly with the ones in the microarray transcriptional profiles. The Se-related genes were categorized into 6 cellular components, 8 molecular functions, 44 biological processes, 10 pathways, and 1 network by STRING. The Se-related gene insulin-like growth factor binding protein 2 (IGFBP2), insulin-like growth factor binding protein 3 (IGFBP3), interleukin 6 (IL6), BCL2, apoptosis regulator (BCL2), and BCL2-associated X, apoptosis regulator (BAX), which involved in many molecular functions, biological processes, and apoptosis pathway may play important roles in the pathogenesis of KBD.
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| 6. |
- Wang, Xi, et al.
(author)
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Gene expression signature in endemic osteoarthritis by microarray analysis
- 2015
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In: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI. - 1661-6596 .- 1422-0067. ; 16:5, s. 11465-11481
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Journal article (peer-reviewed)abstract
- Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based gene signature for the detection of KBD. Previously published gene expression profile data on cartilage and peripheral blood mononuclear cells (PBMCs) from adults with KBD were compared to select potential target genes. Microarray analysis was conducted to evaluate the expression of the target genes in a cohort of 100 KBD patients and 100 healthy controls. A gene expression signature was identified using a training set, which was subsequently validated using an independent test set with a minimum redundancy maximum relevance (mRMR) algorithm and support vector machine (SVM) algorithm. Fifty unique genes were differentially expressed between KBD patients and healthy controls. A 20-gene signature was identified that distinguished between KBD patients and controls with 90% accuracy, 85% sensitivity, and 95% specificity. This study identified a 20-gene signature that accurately distinguishes between patients with KBD and controls using peripheral blood samples. These results promote the further development of blood-based genetic biomarkers for detection of KBD.
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| 7. |
- Wang, Ying, et al.
(author)
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Preliminary exploration of hsa_circ_0032131 levels in peripheral blood as a potential diagnostic biomarker of osteoarthritis
- 2019
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In: Genetic Testing and Molecular Biomarkers. - : Mary Ann Liebert. - 1945-0265 .- 1945-0257. ; 23:10, s. 717-721
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Journal article (peer-reviewed)abstract
- Background: Osteoarthritis (OA) is a common chronic degenerative joint disease characterized by articular cartilage degeneration and synovitis. CircRNAs are increasingly being recognized as functional endogenous RNAs with a stable structure and high tissue specificity. Recent studies have shown that some circRNAs may be involved in the initiation and progression of OA and that there is differential expression of circRNAs in chondrocytes in vitro isolated from patients with OA.Purposes: In this study, we aimed to determine if circRNA levels in the peripheral blood of Chinese Han patients with OA would be diagnostic based on the previous in vitro studies.Methods: We collected peripheral blood samples from 25 patients suffering from OA and 25 healthy controls and measured hsa_circ_0032131_CBC1 RNA levels through quantitative RT-PCR (qRT-PCR). The statistical basis for evaluating the diagnostic value was to calculate the area under the receiver operator characteristic (ROC) curve.Results: The results of the qRT-PCR for hsa_circ_0032131_CBC1 were consistent with those of the microarray analysis. The ROC curve shows that hsa_circ_0032131 holds diagnostic value for OA (0.8455, p < 0.01).Conclusions: Our research indicates that differentially expressed circRNAs may be involved in the development of OA and could be used diagnostically.
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| 8. |
- Wang, Ying, et al.
(author)
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Screening for differentially expressed circRNA between Kashin–Beck disease and osteoarthritis patients based on circRNA chips
- 2020
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In: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 501, s. 92-101
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Journal article (peer-reviewed)abstract
- Objective: This research aims to explore differentially expressed circRNA between OA and KBD and potential diagnostic biomarkers.Methods: Total RNA was extracted from 5 pairs of KBD and OA knee joint cartilage specimens, and the expression of circRNAs was analyzed by Chip Scanning Analysis. The microarray data was verified by quantitative polymerase chain reaction (qRT-PCR). CircRNA-miRNA network was constructed to predict targeting microRNAs of circRNA genes. Peripheral blood samples from 25 KBD patients and 25 OA patients were collected for verification by qRT-PCR. Diagnostic value was evaluated by the area under the receiver operator characteristic (ROC) curve.Results: A total of 1627 circRNAs were differentially expressed between OA and KBD. Five bone and joint disease-related circRNAs were chosen for qRT-PCR validation. The difference in expression profile of hsa_circRNA_0020014 was confirmed by qRT-PCR, and its circRNA-miRNA regulation network was set up. The ROC curve demonstrated that hsa_circ_0020014_CBC1 in peripheral blood could distinguish patients with KBD and OA.Conclusion: The expression profiles of circRNA were significantly different between OA and KBD. hsa_circRNA_0020014 is a potential biomarker for differential diagnosis between these two diseases.
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| 9. |
- Wang, Ying, et al.
(author)
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Screening for Differentially Expressed Circular RNAs in the Cartilage of Osteoarthritis Patients for Their Diagnostic Value
- 2019
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In: Genetic Testing and Molecular Biomarkers. - : Mary Ann Liebert. - 1945-0265 .- 1945-0257. ; 23:10, s. 706-716
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Journal article (peer-reviewed)abstract
- Background: Osteoarthritis (OA) is the most prevalent osteoarticular disease, which typically involves chronic cartilage degeneration and synovitis. The latest research shows that circular RNAs (circRNAs) play a role in the development of a variety of diseases, including osteoarthrosis.Purposes: The aim of this study was to explore the expression of circRNAs in OA chondrocytes and predict biomarkers for diagnosis.Materials and Methods: The circRNA expression profile was analyzed through use of the Gene Spring software V13.0; differentially expressed circRNAs were screened by comparing OA chondrocytes and normal articular chondrocytes. We validated the microarray data by quantitative real-time polymerase chain reaction analyses of OA chondrocytes and chondrocytes from normal controls. TargetScan software and miRanda software were used to predict networks of circRNA–miRNA interactions in cartilage. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were applied to predict the functions of differentially expressed circRNAs.Results: Overall, 1380 circRNAs were differentially expressed between OA chondrocytes and normal articular chondrocytes (fold-change ≥2, p ≤ 0.05), including 215 that were upregulated and 1165 that were downregulated circRNAs. After analyzing the differentially expressed circRNA genes, the top 20 enriched GO entries and KEGG pathways were annotated. The hsa_circrna_0032131 was identified for further analysis. A circRNA–miRNA network was constructed to represent the 10 most likely target genes associated with the validated circRNA.Conclusions: Our research suggests that some of the differentially expressed circRNAs in OA chondrocytes compared to normal chondrocytes are etiologically associated with the pathological process of OA. It was found that hsa_circRNA_0032131 likely participates in the initiation and progression of OA and has potential as a diagnostic marker.Clinical Relevance: To analyze the difference of circRNA expression profiles between OA and normal controls and explore biomarkers for diagnosis.
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| 10. |
- Wu, Cuiyan, et al.
(author)
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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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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Journal article (peer-reviewed)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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