Marrow Adipose Tissue Functions: Studying Lipotoxicity in Hip Replacement Candidates

Research Opportunity
PhD students, Masters by Research, Honours students
Number of Honour Places Available
1
Number of Master Places Available
1
Department / Centre
Medicine and Radiology
Location
Western Health
Primary Supervisor Email Number Webpage
Professor Gustavo Duque gustavo.duque@unimelb.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr Ebrahim Bani Hassan ebrahim.bani@unimelb.edu.au Personal web page

Summary Seven million Australians (28%) have musculoskeletal conditions, resulting in the fourth largest overall contributor to direct health expenditure in Australia, accounting for 8.7% ($5.690 billion) of total health-care expenditure, above all types of cancers combined (AIHW 2014).1 The majority of expenses are spent on two conditions: osteoporosis (OP) with associated fractures and osteoarthritis (OA). Yearly 144,000 older Australians sustain osteoporotic fractures at a significant cost of greater than $3.36 billion, excluding the burden, morbidity and mortality associated with osteoporotic fractures.2

Project Details

We already know that as we age fat moves from under skin (subcutaneous fat) into our abdomen and bone marrow (ectopic fat). This relocation and expansion of marrow adipose tissue (MAT) is accompanied by severe decline in human bone volume. To investigate whether expansion of MAT in the bone marrow can drive osteoporosis, we have shown in a mouse model that with ageing, MAT accumulates in bone marrow and causes a state called lipotoxicity. Lipotoxicity involves production of many inflammatory factors and fatty acids by fat cells (adipocytes) that have been shown to be toxic to other cells. Lipotoxicity can severely impair function and survival of osteoblasts (bone-forming cells). Consequently, osteoblasts may produce an anomalous bone organic matrix and mineralise it abnormally too; rendering fragile bone. Armed concrete analogy applies to bones where collagen fibres act like metal rods and hydroxyapatite functions like cement around the metal; and low quality or quantity of each can decrease concrete strength by many folds. However, the roles of lipotoxicity in initiation and progression of OP and risk of fractures has not been studied in humans; and if it is proven in a human study that marrow lipotoxicity drives osteoporosis, the treatment of osteoporosis and prevention of osteoporotic fractures can significantly improve.

We will study the molecular mechanisms of lipotoxicity in the samples collected from hip fracture patients and controls, and will investigate the bone and hematopoietic marrow (HPM) to study the effects of lipotoxicity using histology and also studying the molecular pathways. The results of this study will shed light on bone, fat and HPM biology, and more importantly might identify mechanisms to prevent or treat OP and OA. The possible main outcomes of the study include: a. A MAT imaging tool to accurately predict bone loss and fracure risk; b. Identification of possible blood markers for MAT expansion and associated marrow lipotoxicity; c. Discovery of possible drug targets to prevent marrow lipotoxicity and associated bone and red marrow atrophy.


School Research Themes

Ageing, Musculoskeletal



Research Opportunities

PhD students, Masters by Research, Honours students
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 / Centre

Medicine and Radiology

Research Node

Western Health

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