Diabetic osteoarthritis : Investigating its causes and discovering interventions using tissue engineered human cartilage
OVERVIEW: People with diabetes have more than twice the risk of developing osteoarthritis than the general population. The aim of this project is to investigate the causal link between diabetes and osteoarthritis using tissue engineered human cartilage and search for effective interventional therapies which can be taken as dietary supplements.
BACKGROUND: The link between diabetes and osteoarthritis is not well-understood, and is not linked to obesity or higher BMI, but considered to be due to the build-up of damaging metabolic end-products in joint cartilage. Despite the huge and increasing incidences of both diabetes and osteoarthritis throughout the world, research on diabetic osteoarthritis (DiOA) is very limited. This is partly because animal models and traditional cell culture are incapable of replicating the disease: e.g. rodent joints are not comparable to humans and cartilage does not grow normally in standard cell culture.
We have overcome this challenge by developing an authentic 3D human cartilage tissue culture model which combines human cells with a hydrogel in order to investigate the causes of disease under controlled in vitro conditions and discover effective treatments. Our 3D-cultured human tissue engineered cartilage system can bridge the critical knowledge gap in understanding diabetes-induced osteoarthritis and lead to the development of effective treatments. Our current data shows that both aspirin and dietary ‘nutraceuticals’ may partially or even completely reverse the damaging effects of elevated glucose levels on cartilage, and therefore present a hugely exciting clinical opportunity to prevent diabetes leading to osteoarthritis.
TRAINING: You will be mentored to develop the skills and confidence of an independent scientific investigator by the end of your PhD, and you will be encouraged to develop your own unique skills portfolio, attend technical training courses and establish novel methods for conducting this highly original research. You will be trained in a wide range of techniques, including human joint biology & dissection, primary cell culture, bioreactor design and development, advanced 3D microscopy, FACS, qPCR and Western analysis. A number of original techniques such as intracellular nanoparticle reporters and mitochondrial analysis are currently being developed in our group. This project has excellent opportunities for extremely interdisciplinary training in tissue engineering, clinical translation and fundamental cell biology.
You will be joining a highly energetic and dynamic lab group, and you will have access to a wide ranging academic and public engagement activities, including patient outreach groups and connections to government science policy. Our lab regularly attends UK and international conferences, and the successful student will have exceptionally good travel opportunities for collaborating with partner laboratories around the world and presenting their research.
The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
This opportunity will remain open until a suitable candidate has been found.
To apply, please send your CV and a covering letter to [Email Address Removed] with a copy to [Email Address Removed]
The successful applicant will be expected to provide the funding for tuition fees and all living expenses as well as research and travel costs of £5000 per year. We currently have funding for a preliminary study from the Dowager Countess Eleanor Peel Trust which supports additional research associated with the project. Details of costs can be found on the University website.
1. Louati K, Vidal C, Berenbaum F, Sellam J. Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis. RMD Open. 2015;1:e000077.
2. Foster NC, Henstock JR, Reinwald Y, El Haj AJ (2015) Dynamic 3D culture: Models of chondrogenesis and endochondral ossification. Birth Defects Res C: Embryo Today 105, 19-33. [link]
3. Kelly TA, Ng KW, Ateshian GA, Hung CT. Analysis of radial variations in material properties and matrix composition of chondrocyte-seeded agarose hydrogel constructs. Osteoarthritis Cartilage. 2009;17:73-82.