Research units - Bone Cell Biology and Disease

Bone Cell Biology and Disease

While it may seem that our bones are unchanging, the structure 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. When this balance is disrupted, diseases like arthritis and osteoporosis develop. Cancers can also tip the balance when they occur in the bone marrow or blood (e.g. leukemias), or when they spread to bone (e.g. breast cancer).

Research Overview

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 (that distribute signals throughout the hard tissue of bone).

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.

Research Themes

Communication between osteoblasts, osteocytes and osteoclasts

Ephrin signalling in osteoblasts

The IL-6 / gp130 family of cytokines and bone

Osteoarthritis and Rheumatoid Arthritis

Osteoblast commitment and osteosarcoma (joint with Carl Walkley, Stem Cell Regulation Unit)

Honours and PhD Projects

The role of EphrinB2 signalling in bone remodelling

gp130 and oncostatin M signalling in bone

Prevention of joint deterioration in osteoarthritis

Staff

Staff image

A/Prof Natalie A Sims
Prof T.J. (Jack) Martin
A/Prof Kong Wah Ng
A/Prof Evange Romas
Dr Nicole C Walsh
Holly Brennan
Ling Yeong Chia
Blessing Crimeen-Irwin
Pat Ho
Narelle McGregor
Farzin Takyar
Brett Tonkin
Emma Walker
Dr Stephen Tonna
Dr Rachelle Johnson
Joshua Johnson
Ingrid Poulton

Publication Highlights

  1. Walker, E.C., McGregor, N.E., Poulton, I.J., Solano, M., Pompolo, S., Fernandes, T.J., Constable, M. J., Nicholson, G.C., Zhang, J.G., Nicola, N.A., Gillespie, M.T., Martin, T. J., & Sims, N.A. Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. Journal of Clinical Investigation. In Press.

  2. Walker, E.C., McGregor, N.E., Poulton, I.J., Pompolo, S., Allan, E.A., Quinn, J.M.W., Gillespie, M.T., Martin, T.J., & Sims, N.A.Cardiotrophin-1 is an Osteoclast-Derived Stimulus of Bone Formation Required for Normal Bone Remodeling. Journal of Bone and Mineral Research. 2008 23(12):2025-2032

  3. Allan, E.H., K.D. Häusler, T. Wei, J. H. Gooi, J.M. Quinn, B. Crimeen-Irwin, N.A. Sims, M.T. Gillespie, J E Onyia, T.J. Martin. EphrinB2 Regulation by Parathyroid Hormone (PTH) and PTHrP Revealed by Molecular Profiling in Differentiating Osteoblasts. J Bone Miner Res. 23(8):1170-81. 2008

  4. Martin, T.J., Sims, N.A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends in Molecular Medicine. 11:76-81, 2005.

  5. Sims, N.A., Green, J.R., Glatt, M., Schlict, S., Martin, T.J., Gillespie, M.T., Martin, T.J., Romas, E. (2004) Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis and Rheumatism. 50, 2338–2346.

  6. Sims, N.A., Jenkins, B.J., Quinn, J.M.W., Glatt, M., Gillespie, M.T., Ernst, M., Martin, T.J. gp130 regulates bone turnover and bone size by distinct downstream signaling pathways Journal of Clinical Investigation 113, 379-389; 2004.

  7. Henderson MA, Danks JA, Slavin JL, Byrnes GL, Choong PFM, Spillane JB, Hopper JL, Martin TJParathyroid hormone-related protein localization in breast cancer predicts improved prognosis. Cancer Research. 66: 2250-2256, 2006.

  8. Fisher JL, Thomas-Mudge RJ, Elliott J, Hards DK, Sims NA, Slavin JL, Martin TJ, Gillespie MT. Osteoprotegerin overexpression in breast cancer cells enhances orthotopic and osseous tumour growth and contrats with that delivered therapeutically. Cancer Research. 66: 3620-3628, 2006.

  9. McKinstry W, Polekhina G, Diefenbach-Jagger H, Ho P, Sato K, Onuma E, Gillespie MT, Martin TJ, Parker MW. Structural basis for antibody discrimination between two antibodies that recognize the parathyroid hormone receptor. J Biol Chem 284: 1557-1563, 2009.

  10. Martin TJ, Gooi JH, Sims NA. Molecular mechanisms in coupling of bone formation to resorption. Critical Reviews in Eukaryotic Gene Regulation. 19: 61-72, 2009.

  11. Fukumoto S, Martin TJ. Bone as an endocrine organ. Trends Endocrinol Metab50: 230-236, 2009.

  12. Askmyr M, Sims NA, Martin TJ, Purton LE. What is the true nature of the osteoblastic hematopoietic stem cell phenotype? Trends Endocrinol Metab 20: 303-309, 2009