About the Project
Bone loss associated with disuse osteoporosis leading to increased fracture risk, represents a huge burden to modern healthcare systems and is a source of great personal misery for those who suffer from this condition. Using an animal skeletal model at the ovine calcaneus, we will examine the effects of experimentally induced mechanical under-loading at both structural and cellular levels in order to mimic the pathological events occurring within disuse osteoporosis in humans.
The main aims of the project will be to determine the extent of bone loss (reduced bone mass) over a range of time points from 3 days to sixteen weeks following the induction of mechanical under-loading. The levels of cellular activity relating to bone turnover will be established as a marker of the onset of bone loss within this system. This will be achieved through histological analysis of tissue sections using tartrate resistant acid phosphatase (TRAP) staining, as a determinant of bone resorption.
Using immunohistchemical staining techniques, molecules expressed by osteocytes known to influence bone turnover will be assessed in relation to skeletal environments associated with low mechanical stain. These candidate molecules will include sclerostin (Poole et. al. 2005), Dkk1 (Power et. al. 2010) and nitric oxide synthase (Loveridge et. al. 2002). Together with an assessment of the contribution of osteocyte apoptosis (Noble et. al, 2003) as a potential driver of increased osteoclastic resportion (using TUNEL staining), determination of the relative expression of these and other important signalling molecules will provide mechanistic insight into the pathophysiological / temporal changes within bone tissue due to disuse osteoporosis.
Funding Notes
Entry requirements: A minimum of 2:1 honours degree or equivalent, in a Bioscience subject.
We welcome year-round applications from Home/EU/Overseas self-funded students and applicants able to secure funding to cover all costs involved with PhD study, including living costs, tuition fees (and bench fees where required).
Overseas candidates should also be competent in English and have achieved, as a minimum, IELTS-6.5
For further details regarding making an application, go to:
http://www.chester.ac.uk/research/degrees
or
For International students (PhD) go to:
http://www.chester.ac.uk/international/apply/research
For informal enquiries regarding this research project email 1st supervisor.
For further details regarding research in Biological Sciences go to:
http://www.chester.ac.uk/departments/biological-sciences/staff
References
Poole, K. E., van Bezooijen, R. L., Loveridge, N., Hamersma, H., Papapoulos, S. E., Löwik, C. W., & Reeve, J. (2005). Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. The FASEB journal, 19(13), 1842-1844.
Power, J., Poole, K. E., van Bezooijen, R., Doube, M., Caballero‐Alías, A. M., Lowik, C., ... & Loveridge, N. (2010). Sclerostin and the regulation of bone formation: effects in hip osteoarthritis and femoral neck fracture. Journal of Bone and Mineral Research, 25(8), 1867-1876.
Loveridge, N., Fletcher, S., Power, J., Caballero-Alias, A. M., Das-Gupta, V., Rushton, N., ... & Pitsillides, A. A. (2002). Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: differences between cases of intracapsular hip fracture and controls. Bone, 30(6), 866-871.
Noble, B. S., Peet, N., Stevens, H. Y., Brabbs, A., Mosley, J. R., Reilly, G. C., Reeve, J., Skerry, T.M., & Lanyon, L. E. (2003). Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. American Journal of Physiology-Cell Physiology, 284(4), C934-C943.
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