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Joint morphogenetic cells in the adult mammalian synovium

Author

Listed:
  • Anke J. Roelofs

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Janja Zupan

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Anna H. K. Riemen

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Karolina Kania

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Sharon Ansboro

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Nathan White

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Susan M. Clark

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

  • Cosimo De Bari

    (Arthritis & Regenerative Medicine Laboratory, Institute of Medical Sciences, University of Aberdeen)

Abstract

The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life.

Suggested Citation

  • Anke J. Roelofs & Janja Zupan & Anna H. K. Riemen & Karolina Kania & Sharon Ansboro & Nathan White & Susan M. Clark & Cosimo De Bari, 2017. "Joint morphogenetic cells in the adult mammalian synovium," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15040
    DOI: 10.1038/ncomms15040
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    Cited by:

    1. Robin Caire & Estelle Audoux & Mireille Thomas & Elisa Dalix & Aurélien Peyron & Killian Rodriguez & Nicola Pordone & Johann Guillemot & Yann Dickerscheit & Hubert Marotte & François Vandenesch & Fréd, 2022. "YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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