There are many diseases that affect the skeleton: these range from common conditions like osteoporosis through to rare bone diseases like osteogenesis imperfecta. Unfortunately, even though we have therapies that can treat the symptoms of bone diseases, there are no cures that can give a patient a healthy skeleton. But we have hope! While it may seem that our bones are unchanging, the skeleton is constantly being renewed so it can adapt to changes in diet and activity levels: some cells dissolve old bone and new replacement bony substance is formed by other cells. By discovering the way these cells behave, we will learn ways to control them so that conditions like osteoporosis and osteogenesis imperfecta can be treated, and so that we can find ways to stop cancers of the bone marrow or blood (e.g. leukemias), and cancers spread to bone (e.g. breast cancer).
Bone is a surprisingly dynamic tissue, continually changing its shape and composition in response to physical exercise, diet and other factors. This is controlled by three cell types within the bone tissue – osteoblasts (that form bone), osteoclasts (that destroy bone) and osteocytes (a network of cells that signal to osteoblasts and osteoclasts).
Our research is focussed on understanding the way these cells communicate with each other to control bone health. Understanding these pathways will help us to develop new methods for the treatment of bone and joint diseases including osteoporosis and arthritis, as well as helping us to understand the growth of cancer within bone, particularly breast cancer, prostate cancer and osteosarcoma.
Our laboratory has defined the mechanisms by which IL-6 family cytokines (including IL-6, IL-11, Oncostatin M, Cardiotrophin-1 and ciliary-neurotrophic factor) influence osteoblasts, osteoclasts and osteocytes. Most recently, we have discovered that these cytokines control the process by which cortical bone (the hard outer shell of the skeleton) forms, and may explain why men have stronger cortical bone than women. In our ongoing work, we are defining which of these cytokines are most important for this process, and how they are controlled in osteocytes by sex-steroid hormones.
Our team discovered PTHrP in 1987 and are continuing to discover new things about how this protein influences the function of cells within the skeleton, including osteocytes. We have recently shown that osteocytes produce PTHrP, and use it to control osteocyte differentiation, bone matrix composition, and bone size. Our ongoing work is defining how different regions of this molecule control osteocyte gene expression, and how this molecule affects embryonic and neonatal bone development.
The amount of bone in the skeleton is not the only thing that makes it strong. If bone is of poor material quality (e.g. less, or more mineralised than normal), it can be weak, and more likely to break. Through our work on the Eph/Ephrin family of tyrosine kinases, we discovered that this protein is important for osteoblasts and osteocytes to control the way that bone becomes a hardened, mineralized tissue. This work, in collaboration with the Australian Synchrotron, is helping us to discover how bone mineral becomes incorporated into the skeleton in a way that makes it strong.