FIGURE 2.

Plasticity of chondrocytes in differentiation, de-differentiation and transdifferentiation. (A) Mesenchymal condensation contains progenitor cells for both joint and growth plate cartilage formation. Cells at the site of future joint undergo dedifferentiation to form the interzone which eventually give rise to different joint components including the articular cartilage. (B) Chondroprogenitors outside the interzone become part of the growth plate cartilage and differentiate into chondrocytes which are located inside individual lacunae and bound with pericellular matrix. Each of these cocoon-like structures is called a “chondron.” Bones elongate through a developmental event called endochondral ossification. Chondrocytes at the central region of the cartilage analgen first undergo hypertrophy. Blood vessels are invaded to induce remodeling of cartilage matrix to mineralized bone matrix. Cartilage is then separated by the primary ossification center into the distal and proximal parts where the growth plates are formed. Before the end of puberty, chondrocytes in the growth plate actively undergo programmed differentiation and transdifferentiation as shown in (C,D), contributing to the formation and elongation of bones. Invasion of blood vessels in-between the articular surface and the growth plates leads to hypertrophy of cells and hence formation of secondary ossification centers at bone ends of a long bone. (C) This roadmap shows the changes of matrix production with the differentiation status of chondroprogenitors-descendant cells. Same color scheme is applied in (A–C) to indicate the fate of each lineage in skeletal tissues. (D) Chondrocytes are not actively migrating to the ossification front during endochondral ossification. Instead, they stay at the same position receiving external cues at specific moment to differentiate and remodel its surrounding matrix. Hypertrophic chondrocytes at the chondro-osseous junction produce enzymes to remove matrix and release themselves to the bone marrow, and transit to stem-cell like progenitors for osteoblasts which will finally differentiate into osteocytes buried in bone. RC, reserved chondrocyte; PC, proliferating chondrocyte; PHC, Pre-hypertrophic chondrocyte; HC, Hypertrophic chondrocyte; SCLP, Stem cells-like progenitors; OB, Osteoblast; OCY, Osteocyte.