Bone marrow adipose tissue and the control of bone mass (HORWOODU19MED)

In the UK over 3 million people have osteoporosis leading to over 300,000 fragility fractures per year: this costs £1.9 billion for hip fractures alone. Low bone mass arises from a number of different causes including diet, ageing, genetic predisposition, autoimmune disorders and diabetes (1, 2). Human cross-sectional studies have established an inverse correlation between bone mass and bone marrow adipose tissue (BMAT) particularly in skeletal ageing and osteoporosis, where high marrow adiposity is closely linked to reduced bone integrity and increased fracture risk (3). Study of different osteoporotic models; induced by ageing, sex hormone deficiency and glucocorticoids, supports these findings (4, 5). BMAT and bone forming osteoblasts arise from the same precursor in the bone marrow, mesenchymal stromal cells (MSCs). Adipokines (i.e. adiponectin, leptin), incretins (GLP1 and GIP), and hormones (i.e. GH and insulin) are involved in the modulation of bone remodelling, marrow adipogenesis, and energy metabolism. Hence, metabolic diseases such as diabetes mellitus greatly affect BMAT, bone strength and fracture risk.

We hypothesise that this relationship relates to fate-switching of MSCs between osteoblastic and adipogenic fates. This project will advance our understanding of how the ageing bone marrow environment selects for the differentiation of MSC into adipocytes at the expense of osteoblasts. We have identified a new receptor involved in this process and will test its role in osteoporosis and diabetes models and in patient cohorts. To do this work we will employ in-vitro assays with clinical samples from the metabolic bone clinic at the Norfolk and Norwich University Hospital as well as in-vivo disease models. As disease prevalence increases with our ageing population, understanding how to alter the balance between bone and BMAT will provide insights to disease mechanisms and importantly, future treatments to ameliorate bone loss.

For more information on the supervisor for this project, please go here: https://people.uea.ac.uk/en/persons/n-horwood
The type of programme: PhD
The start date of the project: OCT 2019
Acceptable first degree in Medicine, Biological Sciences and minimum entry requirements is 2:1.