FIGURE 3.

Development and elongation of endochondral bones. Phases of endochondral bone development: A, cell adhesion and ECM secretion (green lines); increased cell division may also occur, B, chondrocyte commitment and cartilaginous matrix production including collagen fibrils (blue), C, perichondrium formation, and D, establishment of the chondrocyte zones and articular cartilage. Proliferation occurs in the reserve zone, proliferating and prehypertrophic zones; orientation of cell division is indicated by arrows. ¹⁹² In the proliferating and prehypertrophic layers, orientated divisions generate a clonal column of cells. The boxed area highlights a dividing cell shown in detail in the higher power schematic; the two daughter cells (blue) initially maintain contact through an N‐CADHERIN rich domain (green) which changes orientation until the cells finally divide. ¹⁹³ , ¹⁹⁴ E, Sheets and rods grow by different mechanisms. ¹⁸⁴ Cell behaviors within the straight and curved regions of the nasal capsule which is shaped by the adjacent epithelium. Gray box: A cell (yellow) within the perichondrium generates a column of cells across the width of the rudiment increasing its length. Orange box: Localized regions of higher BMP signaling generate a disorganized aggregate of cells from a single perichondral stem cell (shown in blue) and cause bending. ¹⁸⁴ , ¹⁹⁷ Purple box: Additional condensations can be recruited into the cartilage element. ¹⁸⁴ The arrows show direction of elongation. F,G, Additional mechanisms of long bone growth: (F) intercalations of short adjacent columns of proliferating cells and, G, hypertrophy, and increased matrix production (dark blue shading) increase the length of the bone. In D,F,G, the short horizontal lines indicate time; LHS, start, RHS, end of process; the orientation of long bone shown in, D