Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament

SRY-box containing gene 9 (Sox9) and scleraxis (Scx) regulate cartilage and tendon formation, respectively. Here we report that murine Scx+/Sox9+ progenitors differentiate into chondrocytes and tenocytes/ligamentocytes to form the junction between cartilage and tendon/ligament. Sox9 lineage tracing in the Scx+ domain revealed that Scx+ progenitors can be subdivided into two distinct populations with regard to their Sox9 expression history: Scx+/Sox9+ and Scx+/Sox9− progenitors. Tenocytes are derived from Scx+/Sox9+ and Scx+/Sox9− progenitors. The closer the tendon is to the cartilaginous primordium, the more tenocytes arise from Scx+/Sox9+ progenitors. Ligamentocytes as well as the annulus fibrosus cells of the intervertebral discs are descendants of Scx+/Sox9+ progenitors. Conditional inactivation of Sox9 in Scx+/Sox9+ cells causes defective formation in the attachment sites of tendons/ligaments into the cartilage, and in the annulus fibrosus of the intervertebral discs. Thus, the Scx+/Sox9+ progenitor pool is a unique multipotent cell population that gives rise to tenocytes, ligamentocytes and chondrocytes for the establishment of the chondro-tendinous/ligamentous junction.