Speaker: Thomas A. Einhorn, MD, Boston University School of Medicine
Location: Seminar Room A, 17th Floor, The Forsyth Institute, 245 First Street, Cambridge
Abstract: Skeletal healing is a highly reproducible process that recapitulates events of skeletal development in utero. Although the method of fracture treatment can influence the cellular and tissue responses, most fractures worldwide heal by a process of endochondral ossification. Using a laboratory model of endochondral fracture healing, we have demonstrated the a membranous bone response from the periosteum and a simultaneous endochondral response adjacent to the fracture site. Mesenchymal stem cells differentiate into chondroblasts and lay down cartilage. Once a critical mass is achieved, and mechanical loads can be transferred across the fracture gap, the newly formed cartilage becomes mineralized, becomes a target for chondroclasts that resorb decalcified cartilage, and is ultimately replaced by woven bone. A related process, known as distraction osteogenesis, is driven by angiogenic events. While in fracture healing, endochondral ossification prevails, in distraction osteogenesis, bone is produced by direct membranous ossification from elements in the bone marrow space. Several experiments have demonstrated that vascular endothelial growth factor and HIF-1ƒÑ are involved in this process.