Browsing by Subject "Osteoclastogenesis"
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Item Analyzing Loss of HDAC4 Expression: Effect on Osteoclastogenesis(2016-06) Lelich, RosemaryHistone deacetylases (HDACs) are intracellular enzymes that directly affect chromatin structure and transcription factor activity. HDACs have become an important focus in research due to their role in many fundamental processes including differentiation, growth arrest and apoptosis. It has been demonstrated that skeletal formation is regulated by HDACs in their ability to repress transcription factors required in osteoblastogenesis and osteoclastogenesis. These findings have immense clinical implications for HDACs as therapeutic agents. In this study, I seek to understand more about the role of a specific HDAC during osteoclast differentiation. It has recently been shown that HDAC7, a Class IIa HDAC, suppresses osteoclastogenesis when over-expressed and that loss of expression increases osteoclastogenesis. These effects are opposite of those reported with loss of Class I HDAC expression and broad spectrum HDAC inhibitors. My experiments are the first to examine another Class IIa HDAC, HDAC 4 and its role during osteoclastogenesis. My results demonstrate loss of HDAC4 expression leads to enhanced osteoclast differentiation and activity. Furthermore in the absence of HDAC7, loss of HDAC4 expression leads to a further enhancement of osteoclast differentiation and activity. Overall my results demonstrate a role for HDAC4 in regulating osteoclast differentiation and activity unique from the role previously demonstrated for HDAC7.Item Histone deacetylase 3 and histone deacetylase 7 Have opposite effects on osteoclast differentiation.(2010-06) Romsa, Amanda MarieHistone deacetylases (HDACs) are negative regulators of transcription. Endochondral bone formation including chrondocyte and osteoblast maturation is regulated by HDACs. Very little is known about the role HDACs play in osteoclast differentiation. This study found that suppression of HDAC3 expression represses osteoclastogenesis, while osteoclasts suppressed for HDAC7 expression had accelerated differentiation compared to control cells.Item The regulation of osteoclastogenesis by bone morphogenetic proteins, twisted gastrulation, and histone deacetylases.(2012-08) Pham, Lan DangBone morphogenetic proteins (BMPs) are well-studied regulators of osteoblasts, and are used in a number of craniofacial and orthopedic procedures to promote localized bone formation. Studies of skeletal tissue has shed light on BMPʼs role as an inducer of chondrocytic and osteoblastic differentiation and function. BMPs have been used successfully in studies to: treat critical sized defects in both long and craniofacial bones; enhance fracture healing; treat nonunions and lumbar spinal fusion; and regenerate alveolar bone and portions of teeth such as dentin and pulp. However, it has been difficult to determine the optimal concentrations, appropriate temporal release, and regulation of BMPs, as both a deficiency and an excess of BMPs may lead to pathologic states. Furthermore, the cellular and molecular origin of this BMP-associated stimulation of bone resorption remains poorly understood. The data presented in this thesis will help us better understand the modulation of osteoclastogenesis and bone resorption by the regulatory proteins BMP-2, Twisted gastrulation, and Histone deacetylase 3 and 7. The knowledge gained by studying these regulators in osteoclasts should provide important new insight into the use of BMPs in bone generation procedures, its role in pathogenesis of bone resorptive disorders, and provide a conceptual framework for the development of successful therapies and bone regenerative strategies for diseases associated with increased bone loss and defective bone formation.