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Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions

Author

Listed:
  • Mojca Frank-Bertoncelj

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Michelle Trenkmann

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Kerstin Klein

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Emmanuel Karouzakis

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Hubert Rehrauer

    (Functional Genomics Center Zurich, ETH Zurich and University of Zurich)

  • Anna Bratus

    (Functional Genomics Center Zurich, ETH Zurich and University of Zurich)

  • Christoph Kolling

    (Schulthess Clinic, Lengghalde 2)

  • Maria Armaka

    (Biomedical Sciences Research Center ‘Alexander Fleming’)

  • Andrew Filer

    (Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital)

  • Beat A. Michel

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Renate E. Gay

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich)

  • Christopher D. Buckley

    (Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital)

  • George Kollias

    (Biomedical Sciences Research Center ‘Alexander Fleming’
    School of Medicine, National and Kapodistrian University of Athens)

  • Steffen Gay

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich
    Center of Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich)

  • Caroline Ospelt

    (Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich
    Center of Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich)

Abstract

A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.

Suggested Citation

  • Mojca Frank-Bertoncelj & Michelle Trenkmann & Kerstin Klein & Emmanuel Karouzakis & Hubert Rehrauer & Anna Bratus & Christoph Kolling & Maria Armaka & Andrew Filer & Beat A. Michel & Renate E. Gay & C, 2017. "Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14852
    DOI: 10.1038/ncomms14852
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