Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.

摘要: The sequence of events that leads to the formation a functionally graded enthesis is not clearly defined. current study demonstrates clonal expansion Gdf5 progenitors contributes linear growth enthesis. Prior mineralization, Col1+ cells in appose Col2+ underlying primary cartilage. At onset at base express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. mineralization front then extends towards tendon midsubstance above become encapsulated mineralized fibrocartilage over time. hedgehog (Hh) pathway regulates this process, Hh-responsive Gli1+ within developing mature from unmineralized fibrochondrocytes response activated signaling. Hh signaling required for tissue-specific deletion its obligate transducer Smoothened significant reductions apposition fibrocartilage. Together, these findings provide spatiotemporal map – embryonic progenitor pool synthesis collagen template finally zonal These results can inform future tendon-to-bone repair strategies create mechanically functional which fibers are anchored bone through