Articular cartilage and joint development from embryogenesis to adulthood

Abstract

Within each synovial joint, the articular cartilage is uniquely adapted to bear dynamic compressive loads and shear forces throughout the joint's range of motion. Injury and age-related degeneration of the articular cartilage often lead to significant pain and disability, as the intrinsic repair capability of the tissue is extremely limited. Current surgical and biological treatment options have been unable to restore cartilage de novo. Before successful clinical cartilage restoration strategies can be developed, a better understanding of how the cartilage forms during normal development is essential. This review focuses on recent progress made towards addressing key questions about articular cartilage morphogenesis, including the origin of synovial joint progenitor cells, postnatal development and growth of the tissue. These advances have provided novel insight into fundamental questions about the developmental biology of articular cartilage, as well as potential cell sources that may participate in joint response to injury.

Keywords: Articular cartilage; Cartilage development; Joint formation; Lineage tracing; Progenitor cells.

Fig. 1

Selective labeling of Gdf5-expressing cells in Gdf5^CreERT2 mice. At birth, Gdf5^Cre;R26R^zsGreen labeled cells are found throughout the joint, including within the articular cartilage (white arrow) and the putative secondary ossification center (yellow arrowhead) (A). After tamoxifen administration at E17.5, Gdf5^CreERT2; R26R^tdTomato labeled cells are less numerous, and more restricted towards the articular cartilage (white arrow) (B). Gdf5^Cre;R26R^zsGreen remain present in all joint tissues through 6 months of age, including within the secondary ossification center (yellow arrowhead, C) as well as the entire thickness of the articular cartilage (E). Gdf5^CreERT2; R26R^tdTomato labeled cells remain restricted primarily to the articular cartilage (white arrows, D-F).

Fig. 2

Cells with a Prg4+ lineage respond to articular cartilage injury. Safranin-O/Fast green staining of mature mouse femoral articular cartilage before (A) and 7 days (B) after creation of a full-thickness chondral defect. After tamoxifen administration to Prg4^CreERT2/R26R^tdTomato mice at 1month of age, labeled cells are found throughout several layers of the articular cartilage (C). One week after injury, cells within the defect site (dotted line) are Prg4+, indicating that cells with a Prg4-expressing lineage participate in the acute injury response (D).