The aim of this thesis was to study mechanotransduction in bone, focusing first on the mechanical stimulus <i>per sé</i> and then looking at the regulation of response to mechanical stimuli in osteoblastic cells, specifically looking at the regulation of nitric oxide. A new system was designed to produce fluid flow and eliminate, or at least reduce, strain and pressure. A system to induce only hydrostatic pressure was also designed. Using these systems, cells were tested for response to pressure and fluid flow. The responses measured were the early expression of the transcription factor c-Fos, and the translocation of β-catenin to the nucleus. Although both types of mechanical stimuli induced the translocation of β-catenin, pressure did not produce an increases in expression of <i>c-fos</i>. This showed the differences in response as a result of different types of stimuli, and is likely caused by the initiation of different signalling pathways by each stimulus. A comprehensive study of the distribution and quantity of caveolae in cells of the osteoblastic lineage was conducted, and this revealed that osteocytes have significantly more caveolae than osteoblasts. The connection between eNOS and mechanotransduction was studied with eNOS null mice, in whole bones and in cultured bone cells. The mechanical and material properties of eNOS null bones were compared to wild type bones. Differences between these were found but were few, indicating the role of eNOS in bone might be minimal and suggesting that the enzyme is only involved in osteoblasts differentiation during development. Nitric oxide production was monitored in bone cells from eNOS null mice. Surprisingly they produced an increased in nitric oxide in response to stimulation by fluid flow. This nitric oxide was inhibited with a specific inducible nitric oxide synthase (iNOS) inhibitor, pointing to iNOS as the enzyme responsible for nitric oxide synthesis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499687 |
| Date | January 2008 |
| Creators | Huesa, Carmen |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25468 |
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