(A) Model of endochondral bone development beginning with mesenchymal cell condensation (i); chondrocyte differentiation and development of the cartilage template (ii); chondrocyte maturation and hypertrophy (iii); separation of cartilage growth regions, vascular invasion, and initiation of both cortical and trabecular bone (iv); and finally generation of the secondary center of ossification that separates AC and GP cartilage during postnatal bone development (v). MC, marrow cavity; 2°, secondary center of ossification. Red lines mark the vasculature, and yellow coloration marks mineralized bone. Black box outlines AC region magnified in B. (B) Graphical representation of the distinct cellular zones in postnatal AC. IZ, intermediate zone; RZ, radial zone; TM, tide mark; ZCC, zone of calcified cartilage; SB, subchondral bone; M, marrow. Vertical lines indicate zones of gene expression. (C) Model outlining the process of chondrogenesis and chondrocyte differentiation. Important markers at each stage of chondrocyte differentiation are listed below the stage at which the genes are expressed. Superscripts indicate the level of gene expression.

(A) Periosteum is a well-microvascularized tissue, consisting of an outer fibrous layer and an inner cambium layer. Children have thicker and better-vascularized cambium layers than adults (i versus ii). (B) The cambium layer contains abundant stem/progenitor cells that can differentiate into bone and cartilage (i). Following fracture or osteotomy, progenitor cells residing in the periosteum are activated and enter the cell cycle (ii), followed by differentiation into osteoblastic and chondrogenic (green) lineage cells (iii). Further differentiation of the osteoblasts and chondrocytes leads to intramembranous bone formation (gray) and a mature cartilage template (blue) (iv). The vascular invasion of the cartilage template (v) coupled with bone formation completes the process of endochondral bone repair (vi).