Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis

Fracture healing and distraction osteogenesis have important applications in orthopedic, maxillofacial, and periodontal treatment. In this review, the cellular and molecular mechanisms that regulate fracture repair are contrasted with bone regeneration that occurs during distraction osteogenesis. While both processes have many common features, unique differences are observed in the temporal appearance and expression of specific molecular factors that regulate each. The relative importance of inflammatory cytokines in normal and diabetic healing, the transforming growth factor beta superfamily of bone morphogenetic mediators, and the process of angiogenesis are discussed as they relate to bone repair. A complete summary of biological activities and functions of various bioactive factors may be found at COPE ( Cytokines & Cells Online Pathfinder Encyclopedia), http://www.copewithcytokines.de/cope.cgi. Abbreviations: TGF, tumor-derived growth factor; BMP, bone morphogenetic protein; TNF, tumor necrosis factor; IL, interleukin; RANKL, receptor activator of nuclear factor-kappaB ligand; Rank, receptor activator of nuclear factor-kappaB receptor; OPG, osteoprotegerin; M-CSF, macrophage colony-stimulating factor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; VEGI, vascular endothelial growth inhibitor; Ang, angiopoietin; PDGF, platelet-derived growth factor; IGF, insulin-derived growth factor; FGF, fibroblast-derived growth factor; PEDF, pigment epithelium-derived factor; and Nrp, neuropilin. All other abbreviations and acronyms are denoted in the text.