Browsing by Subject "Oral biology"

Now showing 1 - 3 of 3
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    Analysis of Skeletal Phenotypes of Matrix-Gla Protein (MGP) and Twisted Gastrulation (Twsg1) Deficient Mice.
    (2010-08) Emery, Ann Elizabeth
    Matrix Gla-Protein (MGP) and Twisted Gastrulation (Twsg) are secreted proteins that reside in the extracellular matrix. MGP is a potent inhibitor of mineralization in both softand hard- tissues. MGP-/- mice exhibit numerous abnormalities, the most severe being aortic calcification that leads to death by approximately two months of age. Despite extensive studies using cartilage and cardiovascular tissues in these mice, little is known about how MGP deficiency affects bone development, specifically the impact on osteoblasts and osteoclasts. Twisted Gastrulation is a modulator of BMP signaling in many tissues. Twsg1 deficient mice exhibit several phenotypes including craniofacial, salivary gland defects, and skeletal defects. Twsg1 has also been implicated in embryo patterning and cartilage development but to date, there has been no study of the bone in these mice. Preliminary analysis using faxitron (x-ray) analysis of MGP and Twsg1 wild type and homozygous deficient mice revealed reduced bone and an osteopenic bone phenotype. The goal of my thesis project was to characterize 1) the in vivo (both dynamic and static) phenotype of Twsg-/- mice and 2) both in vivo and in vitro (static) skeletal phenotype of MGP-/- mice. Using microcomputer tomography (μCT), both static, and in the case of Twsg1, dynamic, histomorphometric analysis was performed to characterize the skeletal phenotype in the animals. In both mouse models there was a significant decrease in both cortical and trabecular bone present. Primary osteoblasts and osteoclasts were used to further characterize the in vitro phenotype in the MGP-/- mouse model. Primary osteoblasts showed premature mineralization and differentiation. Bone sialoprotein (BSP) and osteoclacin (OCN) mRNA levels were both elevated. Surprisingly, osteoclast differentiation also showed enhancement with increased number and larger multinuclear TRAP+ osteoclasts. They also showed increases in DC-STAMP and TRAP mRNA levels compared to the wild type animals. The data collected in this study was used to evaluate the skeletal phenotype of the MGP and Twsg1-knockout mouse models to better understand the relationship of osteoporosis, BMP signaling, and mineral metabolism.
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    Investigation of the role of chondroitin sulfate proteoglycan in causing treatment resistance in melanoma to PI3k/mTOR inhibition.
    (2012-07) Javaid, Sehrish
    Melanoma is one of the deadliest tumors. Despite the advances in understanding the melanoma cell biology and drug discoveries, treatment resistance remains a challenge. Chondroitin sulfate proteoglycan (CSPG4) is expressed on the surface of melanoma cells, and its role in metastatic progression has been established. One known mechanism responsible for this activity is modulation of the activity of ERK1,2. PI3k/mTOR pathway is also frequently deregulated in melanomas . We therefore investigated if CSPG4 has an impact on PI3K/mTOR pathway activity. Our results indicate that CSPG4 causes resistance to growth inhibition and apoptosis in early stage melanoma cell lines. The knockdown of CSPG4 sensitized the advanced disease stage cell lines to growth inhibition. CSPG4 also induced resistance at various levels of mTOR pathway in different cell lines, and resulted in inhibition of motility and invasion in response to treatment with PF-05212384, a potent PI3K/mTOR inhibitor. Melanoma cell lines derived from all stages of melanoma growth showed resistance to inhibition of 4ebp1. Our results indicate that CSPG4 play a role in decreased sensitivity of melanoma cells to mTOR pathway inhibition.
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    Nature-inspired shape optimization of dental restoration for replacing single missing tooth
    (2014-08) Chen, Yung-Chung
    The purpose of this research was to explore the various features of a natural tooth's inherent structural design of a natural tooth that enable it to perform its mechanical functions effectively, and then to apply the principles and techniques inspired by these investigations to the design of prostheses for replacing a single missing tooth. The biomechanical analysis of the natural tooth was performed on both a macroscopic (overall shape as determined by its anatomy) and a microscopic (effect of microstructures on bulk material properties and their distribution) scale. The nature-inspired design guidelines were then implemented within a FE framework for optimizing dental prostheses designs. Finally, the mechanical performances of the optimal designs derived from the numerical models were validated with in vitro tests.