Uniform TitleIdentification of a key regulatory pathway in bone regeneration using a novel mouse fracture model
NameManigrasso, Michaele Beth (author), O'Connor, James (chair), Parsons, John (internal member), Denhardt, David (internal member), Harten, Robert (outside member), Gaussin, Vinciane (outside member), Rutgers University, Graduate School - New Brunswick,
Bones--Wounds and injuries--Treatment
DescriptionFracture healing is the complex biological process that restores broken bones to their original shape and function. While the fracture repair process follows a definitive sequence of events, not all the molecular or chemical pathways are completely understood. The development of animals with targeted mutations has allowed for the examination of specific fracture healing pathways, making the use of the mouse model an increasingly valuable tool in the field of orthopaedics. Additionally, evaluating the healing tissues using a torsional mechanical testing protocol is more reproducible and provides a better estimate of the biomechanical properties. Therefore, the first section of this dissertation is focused on the development and characterization of a murine femoral fracture model suitable for torsional mechanical testing. The model developed was tested using radiography, histology and mechanical testing and was shown to be comparable to other published femoral fracture models. After validation of this model, the next experiment focused on exploring how a complex phenotype, such as bone mineral density, may affect bone healing. Using inbred strains of mice with established bone mineral density values, the radiographic, histologic and biomechanical analyses of the healing femurs were evaluated. This data showed that having a high bone mineral density actually results in lower mechanical properties and therefore may be deleterious to fracture repair. Finally, this mouse fracture model was used to see how altering the arachidonic acid pathway affects fracture healing. Using genetically modified mice and the fracture and mechanical testing protocols as described, the role of the arachidonic acid pathway in fracture repair was examined. This data showed that either inhibition or acceleration of fracture repair is achieved by manipulating this pathway.
NoteIncludes bibliographical references (p. 154-175).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.