English: Endochondral Fracture Schematic: A fracture that is not rigidly stabilized will heal through a combination of intramembranous and endochondral ossification. Fracture healing progression: bone is depicted in red and cartilage in blue, time course corresponds to healing in a mouse tibia. (A) The first stage of fracture healing is formation of a hematoma to initiate an inflammatory cascade characterized in part by an abundance of pro-inflammatory M1 macrophages, low pH, and elevated lactate level. (B) Next, local osteochondral progenitors differentiate into bone and cartilage to initiate healing. Intramembranous ossification occurs primarily at the periosteum and endosteum of the fracture callus, while the soft cartilage callus forms in the central portion of the fracture where there is maximal mobility. For healing to progress normally, inflammation must be down-regulated and there is a shift in the macrophage population from a pro-inflammatory M1 state to an anti-inflammatory M2 state. (B’) Within the cartilage callus chondrocytes differentiate and mature in a parallel fashion to the growth plate. (C) Conversion of cartilage to bone during endochondral ossification occurs concomitantly with the invasion of blood vessels. (C’) Blood vessels lead to mineralization of the cartilage matrix and new data suggest that these cells transform directly into osteoblasts. Chondrocytes do not undergo significant apoptosis and may re-enter the cell cycle. (D) The cartilage callus becomes fully converted to a trabeculated bone that will bridge the full fracture defect. This trabeculated structure will be remodeled into a cortical bone that is almost indistinguishable in form and function from the native bone.