Joint morphogenetic cells in the adult mammalian synovium

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 -GFP high 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. The stem cells that maintain and repair adult joint tissues in mammals, including articular cartilage, remain incompletely defined. Here the authors perform lineage tracing studies in adult mice and find an ontogenetically defined progenitor cell population that is functional in the synovial joint and distinct from previously reported mesenchymal stem cell populations.