Bone 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.
University of Minnesota Ph.D. dissertation. August 2012. Major: Oral Biology. Advisor: Kim Mansky PhD. 1 computer file (PDF); xii, 170 pages.
Pham, Lan Dang.
The regulation of osteoclastogenesis by bone morphogenetic proteins, twisted gastrulation, and histone deacetylases..
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