Under the direction of Dr. Samuel Lynch at the Institute of Molecular Biology and at the Harvard School of Medicine. I have had the opportunity to focus by research training on the molecular and cellular biology of bone. Within the scope of my current work, three key areas are being explored: (1) The molecular mechanisms of bone formation due to polypeptide growth factors, (2) the in vivo application of growth factors in periodontal wound healing, and (3) the role of bone matrix proteins (osteocalcin and ICIP telopeptide) as markers of periodontal osseous destruction. Polypeptides growth factors are a class of biologic mediators which promote the proliferation, migration, and matrix synthesis of nearly all cells. Polypeptide growth factors have been found in large quantities in bone matrix. The role of growth factors in bone formation is not well understood, however it is hypothesized that they are produced by osteoblasts, sequestered in bone matrix and can be released by and act on bone cells in an autocrine or paracrine manner. The in vitro bone cell culture studies described here utilize a fetal bovine osteoblast system which appears to follow in vivo bone formation in a temporal manner. Various techniques in cellular and molecular biology are being utilized to explore the role of endogenous growth factors during bone formation in this system. Preliminary results have demonstrated the release of Platelet-derived growth factor (PDGF)-like mitogens from the mineralizing osteoblasts by the use of immunoneutralization, immunofluorsecence and in situ hybridization by correlating PDGF-expression with mineral deposition, osteoblast differentiated phenotype and collagen expression. Moreover, other studies have assessed the effects of exogenous growth factors singularly and in combination of osteoblast mitogenesis and collagen biosynthesis. These studies have found that combinations of growth factors (e.g. bFGF + IGF-I or PDGF + IGF-I) promote greater proliferation and matrix synthesis of cells than the single factors. The second component of these studies investigates the use of polypeptide growth factors in in vivo periodontal wound healing. In these experiments the topical application of PDGF, IGF-I, and the combination of both factors was assessed in promoting periodontal regeneration. The studies utilized cynamolgous monkeys with ligature-induced periodontitis. The growth factor treatments were divided into 3 groups in a split-mouth design with the contralateral quadrants serving as controls. The results of growth factor treatment at 4 and 12 weeks post-application demonstrated enhanced periodontal regeneration with the PDGF/IGF-I growth factor combination. Results were attained by histomorphometric analysis of tissue sections showing increases in new bone height and area, as well as new connective tissue attachment. The results from this study further substantiate the use of growth factors in promoting osteogenesis and periodontal wound healing, The third component of my research training involves the diagnosis of periodontal bone destruction following active disease induction. These ongoing studies have utilized Beagle dogs with ligature-induced disease and measure gingival crevicular fluid (GCF) components of bone specific proteins (i.e. osteocalcin and telopeptide pyridinoline cross-links (ICTP). Preliminary results have demonstrated that ICTP can be detected in GCF prior to radiographic bone loss while osteocalcin is found coincident with periodontal bony destruction. The findings of these studies seek to extend the basic and clinical knowledge of factors responsible for bone formation and resorption as it relates to both periodontal and orthopedic bone metabolism. Key Words: Growth Factors, Bone Formation, Regeneration, Periodontal diagnosis.
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