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  • Liu, HuanSchool 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 (author)

The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2021-08-06
  • John Wiley & Sons,2022
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:umu-186450
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-186450URI
  • https://doi.org/10.1111/febs.16143DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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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.

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  • Wu, CuiyanSchool 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 (author)
  • Zhao, HongmouDepartment of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (author)
  • Zhang, Feng'eSchool 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 (author)
  • Zhao, GuanghuiDepartment of Joint Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (author)
  • Lin, XialuSchool 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 (author)
  • Wang, SenSchool 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 (author)
  • Wang, XiSchool 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 (author)
  • Yu, FangfangSchool 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 (author)
  • Ning, YujieSchool 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 (author)
  • Yang, LeiSchool 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 (author)
  • Liu, PeilongDepartment of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (author)
  • Zhang, FengSchool 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 (author)
  • Xu, PengDepartment of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (author)
  • Qu, Chengjuan,1967-Umeå universitet,Institutionen för odontologi(Swepub:umu)chqu0007 (author)
  • Lammi, Mikko,1961-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(Swepub:umu)mila0077 (author)
  • Guo, XiongSchool 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 (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. ChinaDepartment of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China (creator_code:org_t)

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  • In:The FEBS Journal: John Wiley & Sons289:1, s. 279-2931742-464X1742-4658

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