ScxLin cells directly form a subset of chondrocytes in temporomandibular joint that are sharply increased in Dmp1-null mice.

It has been assumed that the secondary cartilage in the temporomandibular joint (TMJ), which is the most complex and mystery joint and expands rapidly after birth, is formed by periochondrium-derived chondrocytes. The TMJ condyle has rich attachment sites of tendon, which is thought to be solely responsible for joint movement with a distinct cell lineage. Here, we used a Scx-Cre ERT2 mouse line (the tracing line for progenitor and mature tendon cells) to track the fate of tendon cells during TMJ postnatal growth. Our data showed a progressive differentiation of Scx lineage cells started at tendon and the fibrous layer, to cells at the prechondroblasts (Sox9 -/Col I +), and then to cells at the chondrocytic layer (Sox9 +/Col I -). Importantly, the Scx + chondrocytes remained as "permanent" chondrocytes to maintain cartilage mass with no further cell trandifferentiation to bone cells. This notion was substantiated in an assessment of these cells in Dmp1 -null mice (a hypophosphatemic rickets model), where there was a significant increase in the number of Scx lineage cells in response to hypophosphatemia. In addition, we showed the origin of disc, which is derived from Scx + cells. Thus, we propose Scx lineage cells play an important role in TMJ postnatal growth by forming the disc and a new subset of Scx + chondrocytes that do not undergo osteogenesis as the Scx - chondrocytes and are sensitive to the level of phosphorous.