Bone turnover has important impacts on bone health. The process modifies weak primary woven bone into the strong lamellar bone, repairs damage in bone, and maintains appropriate calcium homeostasis. The process relies heavily on controlled osteoclastic resorption by dissolution of mineral in the area undergoing remodelling. Bone degenerative diseases occur when the balance between bone resorption and deposition of new bone in the turnover process is altered. Bone is a nanocomposite material composed of a mineral phase (calcium phosphate) deposited within an organic matrix. In spite of the intensive research on the subject, the precise molecular structure of the bone mineral is still an open question. The incorporation of citrate within the mineral structure introduced by Davies et al has provide a more comprehensive structural model that could explain many observations in terms of the mineral structure. Based on this new structural model, a hypothesis has been proposed: that other metabolites similar to citrate can be incorporated into the mineral structure, and differences in metabolite incorporation cause fundamental differences in the physical properties of bone mineral. Thus understanding the effect of metabolite incorporation on the physical properties of bone mineral will lead to insight into the molecular mechanisms of bone degenerative diseases and provide a link between bone quality and bone cell function that is currently missing. Chapter 1 provides overview of the bone composite and formation, and changes in its properties during ageing. The development of the mineral structural model is described and the shortcoming of existing models are assessed. Chapter 2 introduces the theoretical foundations of solid-state NMR spectroscopy, which is the primary analytical method employed in this study, followed by specific experimental techniques that have been used in this work. Chapter 3 described the characterisation of seven different OCP-metabolite composites that have been synthesized in this work, and proposes possible structural model for these composites based on an NMR crystallography approach to determine a structural model for one of the synthetic OCP-metabolite compounds, OCP-SUC. In Chapter 4, the dissolution rate of OCP-metabolites is measured in acidic solution to mimic the resorption process by osteoclasts and assess the possible effects of different incorporated metabolites on the solubility of bone mineral. Finally, Chapter 5 summarises the conclusions from the work and suggests the next steps that arise from this work to uncover the complete molecular structure of bone mineral and its variability in disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:744705 |
| Date | January 2018 |
| Creators | Li, Yang |
| Contributors | Duer, Melinda |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.repository.cam.ac.uk/handle/1810/274877 |
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