Joint morphogenetic cells in the adult mammalian synovium

Anke J Roelofs, Janja Zupan, Anna Helene Katrin Riemen, Karolina Kania, Sharon Ansboro, Nathan White, Susan M Clark, Cosimo De Bari

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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.
Original languageEnglish
Article number15040
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 16 May 2017

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Keywords

  • cartilage
  • mesenchymal stem cells
  • stem-cell research

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