Articular Cartilage: Structural and Developmental Intricacies and Questions

Abstract

Articular cartilage has obvious and fundamental roles in joint function and body movement. Much is known about its organization, extracellular matrix, and phenotypic properties of its cells, but less is known about its developmental biology. Incipient articular cartilage in late embryos and neonates is a thin tissue with scanty matrix and small cells, while adult tissue is thick and zonal and contains large cells and abundant matrix. What remains unclear is not only how incipient articular cartilage forms, but how it then grows and matures into a functional, complex, and multifaceted structure. This review focuses on recent and exciting discoveries on the developmental biology and growth of articular cartilage, frames them within the context of classic studies, and points to lingering questions and research goals. Advances in this research area will have significant relevance to basic science, and also considerable translational value to design superior cartilage repair and regeneration strategies.

Keywords: Articular cartilage; Extracellular matrix; Joint disease; Joint formation; Lineage tracing; Progenitor cells.

Figure 1

Prenatal and postnatal analyses of developing and growing mouse limb joints. (A–C) In situ hybridization showing that at E13.5 Gdf-5 is expressed in interzone cells as well as cells immediately surrounding the joint site and outside the cartilaginous anlagen (dashed vertical lines) (A), and becomes more restricted to the developing joint by E14.5 and E15.5 (B–C). Hybridization signal is pseudo-colored in green. (D) Genetic cell lineage tracing with Gdf5Cre/ROSAmTmG mice reveals that Gdf-5-lineage cells (green) give rise to multiple joint tissues, including the articular cartilage (AC), synovial lining (SL) and capsule tissue. It should be noted that majority of cells within these tissues are reporter-positive. (E–G) Images of proximal tibia articular cartilage sections from neonatal to juvenile mice stained with Safranin O-Fast green. (E) At P0, the incipient articular cartilage (AC) is thin, matrix-poor and made of small flat cells. At this stage, the tissue is molecularly defined by expression of genes including Prg4 and tenascin-C and lack of expression of matrillin-1 and Ucma and is made entirely of Gdf5-lineage cells (see text). (F) By P14, articular cartilage is much thicker and contains abundant matrix and large cells many of which are scattered isotropically through the tissue. (G) By 6 weeks of age, the tissue exhibits a mature organization with distinct zones and a columnar organization of the chondrocytes.