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Journal of Dental Research
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CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE

Molecular Mechanisms Controlling Bone Formation during Fracture Healing and Distraction Osteogenesis

Z.S. AI-Aql1,2, A.S. Alagl3, D.T. Graves4, L.C. Gerstenfeld1 and T.A. Einhorn1,*

1 Orthopaedic Surgical Research Laboratory, Department of Orthopaedic Surgery, Boston University Medical Center, Doctors’ Office Building, Suite 808, 720 Harrison Avenue, Boston, MA 02118, USA;
2 Department of Orthodontics and
4 Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA; and
3 Department of Preventive Dental Sciences, College of Dentistry, King Faisal University, Alkhobar, Saudi Arabia, 31952

Correspondence: * corresponding author, Thomas.Einhorn{at}bmc.org

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.

Key Words: Fracture healing • distraction osteogenesis • morphogens • cytokines

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 • Nrp, neuropilin • All other abbreviations and acronyms are denoted in the text

Journal of Dental Research, Vol. 87, No. 2, 107-118 (2008)
DOI: 10.1177/154405910808700215
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