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The first human ind...
The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway
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- Liu, Huan (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Wu, Cuiyan (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Zhao, Hongmou (author)
- Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
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- Zhang, Feng'e (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Zhao, Guanghui (author)
- Department of Joint Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
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- Lin, Xialu (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Wang, Sen (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Wang, Xi (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Yu, Fangfang (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Ning, Yujie (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Yang, Lei (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Liu, Peilong (author)
- Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
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- Zhang, Feng (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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- Xu, Peng (author)
- Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
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- Qu, Chengjuan, 1967- (author)
- Umeå universitet,Institutionen för odontologi
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- Lammi, Mikko, 1961- (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),School of Public Health, Health Science Center of Xi'an Jiaotong University, China,Chondrogenic and osteogenic differentiation
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- Guo, Xiong (author)
- School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China
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School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, PR. China Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (creator_code:org_t)
- 2021-08-06
- 2022
- English.
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In: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:1, s. 279-293
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Ortopedi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Orthopaedics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Chondrogenesis
- Disease model
- Heparan sulfate proteoglycans
- Human induced pluripotent stem cells
- Kashin-Beck disease
- cellforskning
- cell research
- Orthopaedics
- ortopedi
- reumatologi
- rheumatology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Liu, Huan
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Wu, Cuiyan
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Zhao, Hongmou
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Zhang, Feng'e
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Zhao, Guanghui
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Lin, Xialu
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show more...
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Wang, Sen
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Wang, Xi
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Yu, Fangfang
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Ning, Yujie
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Yang, Lei
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Liu, Peilong
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Zhang, Feng
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Xu, Peng
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Qu, Chengjuan, 1 ...
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Lammi, Mikko, 19 ...
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Guo, Xiong
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- Articles in the publication
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The FEBS Journal
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Umeå University