GLUCOCORTICOID EFFECTS ON BONE: THE ROLE OF THE OSTEOBLAST

Funded Activity Summary

Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, cartilage and skin, causing osteoporosis, muscle wasting and skin damage. As a matter of fact, cortisone-induced muscle and bone disease is one of the most frequent and serious side effects associated with glucocorticoid treatment, and substantially affects quality of life and co-morbidity in many patients. In the present project, we aim to develop new strategies for the understanding and prevention of costisone-induced bone disease. The first step is to investigate the mechanisms of actions of glucocorticoids in bone. To this aim, we have generated a model in which a cortisone- inactivating enzyme is produced in excess in the bone forming cells (osteoblasts). Previous studies have shown that these cells are protected against the effects on cortisone, while other cells not producing this enzyme remained vulnerable. We now intend to use this model to study the mechanisms of glucocorticoid action on bone and muscle under normal and diseased conditions (e.g. in a model of glucocorticoid excess and in a model of rheumatoid arthritis). We also intend to study how internal glucocorticoids affect the development of bone forming cells. Our long-term aim is to uncover new ways to target drug action to the desired tissues and cells, while protecting other tissues and cells from deleterious side effects.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $464,520.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Endocrinology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

11beta-hydroxysteroid dehydrogenase | Bone Biology | Glucocorticoid Prereceptor Regulation and Metabolism | Glucocorticoid-induced Osteoporosis and Bone Loss | Musculoskeletal side effects of glucocorticoids | Osteoblasts and Osteogenesis | Osteoporosis and Metabolic Bone Disease | Prevention of glucocorticoid-induced side effects | Transgenesis | Transplantation, Asthma and Rheumatoid Arthritis

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