Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

By using wide transcriptome analysis, these authors unraveled distinct fingerprints for human articular and growth plate cartilage and identified bone morphogenetic protein (BMP) and Wnt signaling inhibitors (GREM1, FRZB and DKK1) as the most differentially expressed. Furthermore, they confirmed the key role of these molecules by in vitro experiments with mouse tibiae explants as well as with human adult bone marrow-derived mesenchymal stem/stromal cells. These results not only provide deeper insights into the molecular divergences between persistent articular cartilage and endochondral tissue but also help to fill the gap between murine models and adult human cell-based studies towards a tighter exchange between the fields of developmental biology and regenerative medicine. Direct and immediate applications may result in improved protocols for stable chondrogenesis by human mesenchymal stem cells for cartilage tissue engineering purposes and, as suggested by the authors, in dissecting the mechanisms of osteoarthritis.