Investigating lipotoxic impacts of fatty acid synthesis on: (1) osteoblasts, and (2) osteoclast, in vitro and (3) Skeletal Muscle

Research Opportunity
Masters by Research, Honours
Number of Honour Places Available
1
Department
Medicine and Radiology
Location
Western Health
Primary Supervisor Email Number Webpage
Associate Professor Damian Myers damianem@unimelb.edu.au Personal web page

Project Details

Bone is a dynamic organ that remodels and changes in composition throughout the lifespan. As a vital organ, bone is required for weight-bearing and motion, for haematopoiesis and energy storage, among others (Suchacki et al. 2017). Dysregulation of remodelling of bone can lead to pathological bone states such as osteoporosis and fractures (Frost 2003). Early in life, a beneficial relationship exists between body weight and bone density as fat mass positively correlates with bone strength and decreased fracture incidence in at-risk populations (Cornish et al. 2002). However, with ageing, high fat mass can have negative impacts on bone. In the elderly, evidence suggests that fat tissue can undergo a toxic shift in which adipocytes secrete excessive lipids, predominantly fatty acids such as palmitic acid (PA) (Gasparrini et al. 2009, Tagliaferri et al. 2015).  The transition for when the benefits of increased adipose tissue in bone results in pathological impacts is unclear (Ilich et al. 2014) and further research is needed into how lipotoxicity affects each of the cells that control bone turnover, the osteoblasts and the osteoclasts.

Hypothesis:  Fatty acid synthase inhibition by CER has been identified as a possible candidate for future treatments of musculoskeletal diseases but the mechanisms of action is not known. We propose that CER may affect either osteoblasts or osteoclasts, individually; however, CER may also affect the coupling that occurs between osteoblasts and pre-osteoclasts during osteoclastogenesis.

In this study we will investigate the impacts of CER on each of the osteoblasts and osteoclasts in in vitro culture as well as the effects of CER on co-cultures of osteoblasts and monocyte/macrophages, the pre-osteoclastic cells.

Outcomes: This project will define whether FAS inhibition affects osteoblasts and osteoclasts in in vitro culture and, also, whether CER may have an impact on bone turnover by affecting osteoclast coupling and osteoclast formation (osteoclastogenesis).


School Research Themes

Musculoskeletal



Research Opportunities

Masters by Research, Honours
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

Western Health

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