Figure 1. Steps in endochondral bone formation (non-demineralized methacrylate sections, toluidine blue and von Kossa stain, developing mouse).

Panel A shows condensations of chondrocytes (*) forming metatarsal anlagen in the paw, with pink-purple metachromasia indicating cartilage matrix being secreted. In panel B, showing sternebrae, chondrocytes in the central area have become hypertrophic (hc). In C, mineralized cartilage (mc, stained black) is seen due to the secretion of matrix vesicles containing mineral by the hypertrophic chondrocytes before blood vessel invasion. The bone collar (bc) is forming (arrow) by the action of osteoblasts differentiated from the perichondrium. In D, bone formation is taking place, with abundant, mineralized bone and a marrow cavity hosting active, hematopoietic bone marrow (bm). Through openings in the bone matrix such as the one indicated by the asterisk (*), vessels have invaded and brought with them stromal cells and mesenchymal stem cells. The position of the chondroosseous junction (coj) at either end of the growing bone is indicated by the arrows, where septoclasts are degrading matrix to permit capillaries to bud into the mineralized cartilage zone. As capillaries elongate, osteoclasts/chondroclasts follow and remove most of the mineralized cartilage. The distance between the COJs increases due to chondrocyte proliferation and hypertrophy at both ends.