Embryonic development of endochondral and membranous bones.
Top: Endochondral and membranous bone development begins with the formation of mesenchymal condensations. Membranous bones are formed directly from condensations of mesenchymal cells, without the formation of a cartilage intermediate cell.
Bottom: These mesenchymal cells give rise to osteoblasts, from which osteocytes arise, in a process termed membranous ossification. In endochondral bone formation, chondrocytes arise from the mesenchymal condensations, while cells at the periphery of the condensations form a perichondrium. Centrally localized chondrocytes actively proliferate before exiting the cell cycle and differentiating into hypertrophic chondrocytes. The sequential differentiation of chondrocytes establishes a unique cellular organization that constitutes the epiphyseal growth plate. At the distal end of the epiphyseal growth plate, hypertrophic chondrocytes further mineralize their own cartilaginous matrix. In parallel to this multistep differentiation pathway, cells form a thin layer of mesenchymal cells, called the periosteum (i.e., osteoblasts), that envelop the cartilage matrix and invade the zone of hypertrophic chondrocytes. Whereas invading osteoclasts degrade the matrix of the zone of hypertrophic chondrocytes, osteoblasts deposit a bone-specific matrix. The partially degraded mineralized cartilage matrix forms a template for deposition of bone matrix by osteoblasts.