Inflammation-induced Osteosarcopenia: Mechanisms and Novel Treatments

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
A/Prof Kulmira Nurgali kulmira.nurgali@unimelb.edu.au Personal web page

Summary Inflammatory bowel disease (IBD), comprising two main pathologies ulcerative colitis and Crohn's disease, affects >85,000 Australians. Almost 50% of patients with IBD are affected by osteoporosis or osteopenia and with risk of bone fracture 40% higher than the general population. Many young Crohn’s disease patients have osteoporosis and 60% of CD patients have sarcopenia when they should be at the peak bone and muscle strength. To date, no therapy proven to be efficacious in IBD-related osteoporosis/sarcopenia.

Project Details

Gut-derived serotonin (GDS) regulates osteoblast proliferation and bone formation. Serotonin increases a cytokine, osteoprotegerin, which inhibits osteoclasts and thereby reduces bone turnover.Inhibition of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis stimulates bone formation in mouse model of ovariectomy-induced bone loss. However, the exact role of GDS on bone metabolism is not fully understood and needs further investigations. Other products of tryptophan metabolism are kynurenine (KYN) and its derivatives. This pathway metabolizes 95% of the dietary tryptophan, starting with the activation of indoleamine-2,3-dioxigenase-1 (IDO-1) converting tryptophan into KYN, which is then converted into picolinic acid. However, inflammation-induced changes in this pathway and its role in IBD-associated osteosarcopenia have not been elucidated. Studies mechanisms, prevention and treatment of IBD-related osteoporosis/sarcopenia are scarce mainly due to the lack of animal models.have an excellent mouse model of spontaneous chronic colitis associated with high level of GDS, fragile bones, low muscle mass and, therefore, are an excellent model to study mechanisms of IBD-related osteosarcopenia.

The main aims of this study are:

1) To determine progression of changes in GDS and KYN pathways and their role in mechanisms underlying osteosarcopenia associated with chronic intestinal inflammation.


School Research Themes

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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