• Recombinant Bone Morphogenetic Protein-2 Induces Up-Regulation of Angiogenesis and Inflammatory Transcripts: Role of Reactive Oxygen Species

      Akeel, Sara K; Department of Oral Biology (2012-12)
      Large bone defects in the oral and maxillofacial region are mostly secondary to tumor resection, gunshot wounds or craniofacial anomalies. Reconstruction of large bone defects remains a clinical challenge despite the ability of bone to regenerate itself after fracture, mainly because bone regeneration requires recruitment of new cells as well as development of new bone tissue in order to restore anatomical and mechanical functions. Several biological and mechanical factors regulate bone formation. Early vascularization plays a critical role in skeletal bone development and bone fracture repair, and without a vascular supply, osteogenesis is impaired (Glowacki 1998; Akeno, Czyzyk-Krzeska et al. 2001; Carano and Filvaroff 2003). Furthermore, in the treatment of bone defects, vascularized bone grafts show less bone remodeling when compared to non-vascularized bone grafts (Cutting and McCarthy 1983; Wang, Yamazaki et al. 1996). This highlights the importance of angiogenesis in bone formation and remodeling. The close proximity of osteoblasts and osteoclasts to endothelial cells during bone formation suggests there is a cross-talk between these cells. Osteogenesis-inducing growth factors, such as bone morphogenetic proteins (BMPs), especially BMP-2 and -7, and vascular endothelial growth factor (VEGF) which is known to have a major role in angiogenesis, have been reported in many studies to play a major role in osteoblast-endothelial cell communication (Mayer, Bertram et al. 2005). The general goal of this study is to understand some of the molecular events that occur at the site of bone healing and the interaction of local growth factors produced by resident cells such as osteoprogenitor and endothelial cells. This will help us in developing techniques that enhance bone formation and provide better integration of bone grafts in the recipient site. Specifically, the aim of this study is to understand the mechanism by which recombinant bone morphogenetic protein-2 (rhBMP-2) induces bone formation and whether or not the effect of rhBMP-2 is through enhancing angiogenesis and inflammation.