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

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.