Figure 7.

Model for the Contribution and Divergence of Progenitor Cells in Joint Formation

A schematic diagram showing the developmental processes of a knee joint.

(A) Formation of the cartilage anlagen containing Sox9-expressing chondrocytes.

(B) Dedifferentiation of Sox9⁺ chondrocytes to Gdf5⁺ interzone cells at the presumptive joint site.

(C) Expansion of the interzone through recruitment of mesenchymal cells from the surrounding and limited proliferation of peripheral Lgr5⁺ cells, and the partitioning of the interzone into specific regions.

(D) Lgr5⁺ interzone cells undergo lineage divergent and differentiate into cells for the different tissues in a mature joint.

(E) Lgr5⁺ interzone cells are multipotent progenitors contributing to all interior structures of the knee joint including cruciate ligaments, articular cartilage, and menisci. Lgr5⁺/Scx⁻/Col22a1⁺ cells are committed progenitors for articular chondrocyte lineage and menisci, whereas Lgr5⁺/Scx⁺/Col22a1⁻ cells are restricted within the ligament lineage.