Expression of Bone Morphogenetic Proteins in Fracture Healing

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Abstract
Fracture healing involves a complex interaction of many local and systemic regulatory factors. Recently, the presence of several bone morphogenetic proteins and their receptors in the fracture healing process has been described. During the early stages of fracture healing, only a minimum number of primitive cells are expressing bone morphogenetic proteins in the fracture callus. As the process of endochondral ossification proceeds, the presence of bone morphogenetic proteins and their receptors increases dramatically, especially in the primitive mesenchymal and chondrocytic cells. While the cartilaginous component of the callus matures with a concomitant decrease in the number of primitive cells, there is a concomitant decrease in presence of bone morphogenetic protein expressing cells. As osteoblasts start to lay down woven bone on the chondroid matrix, these osteoblastic cells express bone morphogenetic proteins and their receptors. The presence of bone morphogenetic proteins decreases, however, as lamellar bone replaces the primitive woven bone. A similar observation is seen in the areas of the callus undergoing intramembranous ossification. Initially, within several days after the fracture, periosteal cells and osteoblasts show intense expression of bone morphogenetic proteins and their receptors. As the woven bone is replaced with mature lamellar bone, the expression of bone morphogenetic protein decreases. These data and the knowledge of bone morphogenetic proteins' strong osteoinductive capacities suggest that individual bone morphogenetic proteins play important yet different roles during fracture repair.