LD2668 .T4 1950 B83 / Master of Science

"February 2005" / Coursework / Bibliography: leaves 212-222. / 222 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / "Distraction osteogenesis is a surgical technique employed for bone lengthening and reconstruction of skeletal deformities. It is a biological process of new bone formation between bone segments gradually separated by incremental traction". "The purpose of this research was to conduct a pilot study to determine whether immersion fixation is adequate for evaluation of BMP-2, VEGF, Type X collagen expression in a sheep model using immunohistochemical techniques, and to evaluate the expression of these factors during the different stages of distraction osteogenesis." --leaf 14. / Thesis (D.Clin.Dent.)--University of Adelaide, Dental School (Orthodontics), 2005

Typescript (photocopy) / 214 leaves, [80] leaves of plates : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 1982

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Dentistry / Master / Master of Orthodontics

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Kinesins are motor proteins responsible for the anterograde transport on microtubules. Kinesin-1 is the first characterized kinesin, and it consists of two heavy chains and two light chains. KIF5B is a form of Kinesin-1 heavy chains that is ubiquitously expressed in mammals. The head domain of KIF5B is responsible for ATP-dependent mechanical movement along microtubules, while the tail region is well-known for its interaction with cell specific cargos. Recent studies reveal a second microtubule binding site in the tail, suggesting special functions of KIF5B in microtubule sliding and bundling. To understand the role of KIF5B in long bone development, a conditional knockout mouse model was generated, in which Kif5b is deleted in early limb mesenchyme using Prx1-cre/LoxP mediated recombination. Unlike Col2a1-cre directed Kif5b knockout in chondrocytes, the expression of Prx1-cre in limb mesenchyme results in Kif5b knockout in both chondrocyte and osteoblast lineages. The Prx1-cre mediated Kif5b conditional knockout mice develop malformed long bones characterized by their bowed shape, shortened length and multiple fractures, which reflects a combination of defects in bone matrix and growth plate. The mutant mice demonstrate impaired bone matrix formation, as indicated by both collagen density reduction and collagen matrix disorganization. Also, the growth plate does not retain its normal organization, and the hypertrophic zone is absent. The KIF5B deficient chondrocytes not only lose planar cell polarity, but also undergo early apoptosis and fail in terminal differentiation. Interestingly, the binucleation rate is significantly increased in these chondrocytes, suggesting a severe cytokinesis defect. Besides, the intracellular retention of extracellular matrix (ECM) molecules and the uneven distribution of ECM in the cartilage imply both blockage and inappropriate direction of secretion. Cytokinetic defect in chondrocytes is closely associated with growth plate abnormality and growth retardation. In Kif5b knockout chondrocytes, cytokinetic defect is also one of the earliest and principal phenotypes. Therefore the underlying mechanism of cytokinetic defect was further investigated at cellular level. Since Kif5b knockout chondrocytes cannot survive in primary culture, RNA interference approach was adopted to generate a Kif5b-knockdown chondrogenic cell line. As expected, the Kif5b knockdown cells demonstrate cytokinetic defects characterized by increased binucleation rate and prolonged cytokinesis phase. In control cells, KIF5B becomes concentrated in the midbody during cytokinesis, and the midbody organization is disrupted in Kif5b knockdown cells. Furthermore, transient expression of full-length KIF5B significantly reduces the binucleation rate of these KIF5B deficient cells, whereas over-expression of a truncated KIF5B (without microtubule binding sites in tail region) cannot rescue the defect. Additionally, KIF5B is found to interact with midbody components PRC1 and Aurora B kinase by GST pull-down assay. This study demonstrates the multiple functions of KIF5B in long bone development and emphasizes its significant role as a key modulator in chondrocyte cytokinesis. More importantly, the study also brings new insights into the mechanisms of cytokinesis: we propose that KIF5B may participate in cytokinesis by regulating the midbody organization and stability via microtubule bundling and transporting or anchoring important components to the midbody. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Increased bone density has been observed following physical training. However, it is not known whether the mechanical forces of muscular contraction, gravitational pull, or a combination of these forces are required to cause this adaptation. Therefore, the purpose of this study was to determine which mechanical force, muscular contraction or gravitational pull, offered the greatest contribution to increased bone mineral content observed following either swim or run training. METHODS: Female Wistar rats were randomly assigned to one of three groups: 1) Sedentary Control (SC; n = 12), 2) Run Trained (RT; 27.7 m/m, 8% incline, 2 hrs/day; n = 20), and 3) Swim Trained (ST; 2 hrs/day, 2Y/ body weight; n = 14). The animals were sacrificed after 9 weeks of training and the humeri and femurs were removed for analysis.RESULTS: Femur weight, length, diameter, and ponderal index (a measure of robustness), and bone mineral content (BMC) were not different between the three treatment groups. However, femur cortical thickness was significantly (p < 0.01) smaller in the RT when compared to ST and SC rats. The ST humeri were significantly (p < 0.05) heavier, wider, and had a greater BMC when compared with those of the RT and SC rats, while cross sectional area was unaffected by physical training. CONCLUSION: The results of this study indicate that the mechanical forces applied by the swim training protocol produced marked bone adaptation in the ST animals following 9 weeks of physical training. Whereas, the combined mechanical and gravitational forces applied during running by the RT rats produced minimal adaptation of bone following 9 weeks of physical training.