Joint morphogenetic cells in the adult mammalian synovium

Nat Commun. 2017 May 16:8:15040. doi: 10.1038/ncomms15040.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Animals
  • Cartilage, Articular / cytology
  • Cartilage, Articular / injuries
  • Cartilage, Articular / physiology*
  • Cell Cycle Proteins
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Chondrocytes / physiology*
  • Female
  • Growth Differentiation Factor 5 / metabolism
  • Humans
  • Hyperplasia / physiopathology
  • Joint Diseases / physiopathology
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Morphogenesis / physiology
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Regeneration / physiology*
  • Synovial Membrane / cytology*
  • Synovial Membrane / injuries
  • Synovial Membrane / metabolism
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • GDF5 protein, human
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5
  • Nuclear Proteins
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YY1AP1 protein, human
  • Yap1 protein, mouse