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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, conditions like bone spurs and osteoporosis develop, or if the new bone formed is not good quality, other disorders like osteogenesis imperfect or hypophosphatemia could be involved. 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

Ephrin signalling in osteoblasts and osteocytes

This project seeks to identify the contributions of Ephrin B2 : Eph B4 signalling in bone formation and to the effects of PTH on bone
Staff: Christina Vrahnas, Blessing Crimeen-Irwin, Ingrid Poulton, Patricia Ho

The IL-6 / gp130 family of cytokines and bone

Local factors that signal through the gp130 receptor play critical roles in a number of diseases. Our group has identified a range of these family members that contribute to normal bone physiology, including cardiotrophin-1, IL-6, IL-11, oncostatin M, and ciliary neurotrophic factor. This project seeks to understand these factors work within bone, and their importance in normal bone physiology.
Staff: Emma Walker, Narelle McGregor, Ingrid Poulton, Holly Brennan, Nicole Walsh, Dae-Chul Cho

Honours and PhD Projects

Staff

  • A/Prof Natalie Sims
  • Prof T.J (Jack) Martin
  • A/Prof Kong Wah Ng
  • A/Prof Evange Romas
  • Blessing Crimeen-Irwin
  • Emma McGowan (nee Walker)
  • Pat Ho
  • Brett Tonkin
  • Narelle McGregor
  • Ingrid Poulton
  • Christina Vrahnas
  • Dae-Chul Cho
  • Niloufar Ansari
  • Melissa Murat

Publication Highlights

  1. Buenzli P, Sims NA Quantifying the osteocyte network in the human skeleton. Bone. Feb 20(75)144-150.
  2. Ng AJM, Walia MK, Smeets MF, Mutsaers AJ, Russell MR, Sims NA, Purton LE, Walsh NC, Martin TJ & Walkley CR. The DNA helicase Recql4 is essential for normal osteoblast proliferation and osteosarcoma formation. PLoS Genetics. 2015 Apr 10;11(4):e1005160.
  3. Chia LY, Martin TJ, Walsh NC, Sims NA. Isolation and gene expression of haematopoietic cell-free preparations of highly purified murine osteocytes. Bone. 2015 Jan;71(1):34-42. 
  4. Standal T, Johnson RW, Brennan HJ, Poulton IJ, McGregor NE, Walker EC, Martin TJ, Sims NA. gp130 signalling in osteocytes is required for the anabolic action of parathyroid hormone. Journal of Endocrinology. 2014 Nov;223(2):181-90.
  5. Seeman E, Martin TJ. Co-administration of Antiresorptive and Anabolic Agents: A Missed Opportunity. J Bone Miner Res. 2015 May;30(5):753-64.
  6. Tonna S, Takyar FM, Vrahnas C, Crimeen-Irwin B, Ho PWM, Poulton IJ, Brennan HJ, McGregor NE, Allan EH, Nguyen H, Forwood MR, Tatarczuch L, Mackie EJ, Martin TJ, Sims NA. EphrinB2 controls osteoblast differentiation and limits apoptosis. FASEB J. 2014 Oct;28(10):4482-96.
  7. Ho PW, Goradia A, Russell MR, Chalk AM, Milley KM, Baker EK, Danks JA, Slavin JL, Walia M, Crimeen-Irwin B, Dickins RA, Martin TJ, Walkley CR. Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo. Oncogene. 2014 Jul 21.
  8. Johnson RW,  Brennan HJ, Vrahnas C, Poulton IJ, McGregor NE, Standal T, Walker EC, Koh T-T, Nguyen H, Walsh NC, Forwood MR, Martin TJ, Sims NA. The primary function of gp130 signalling in osteoblasts is to maintain bone formation and strength, rather than promote osteoclast formation. Journal of Bone and Mineral Research. 2014 Jun;29(6):1492-505.
  9. Gooi JH*, Chia LY*, Walsh NC, Karsdal MA, Quinn JMW, Martin TJ, Sims NA. Decline in calcitonin receptor expression in osteocytes with age. *, equal first authors. Journal of Endocrinology. 2014 221(2):181-191.
  10. Sims NA, Ng KW. Implications of osteoblast-osteoclast interactions in the management of osteoporosis by anti-resorptive agents Denosumab and Odanacatib. Current Osteoporosis Reports. 2014 12(1):98-106.
  11. Johnson RW, White JD, Walker EC, Martin TJ, Sims NA. Myokines (muscle-derived cytokines and chemokines) including ciliary neurotrophic factor (CNTF) inhibit osteoblast differentiation. Bone. 2014 64:47-56.
  12. Takyar FM, Tonna S, Ho PWM, Crimeen-Irwin B, Baker EK, Martin TJ, Sims NA. EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone. Journal of Bone and Mineral Research. 2013 Apr;28(4):912-25. Awarded the Sol Posen Award for Research Excellence by the ANZBMS.
  13.  Walker EC, Poulton IJ, McGregor NE, Ho PWM, Allan EH, Quach JM, Martin TJ, Sims NA. Sustained RANKL response to parathyroid hormone in oncostatin M receptor-deficient osteoblasts converts anabolic treatment to a catabolic effect. Journal of Bone and Mineral Research. 2012;27:902-912.
  14. Poulton IJ, McGregor NE, Pompolo S, Walker EC, Sims NA. Contrasting roles of leukemia inhibitory factor (LIF) in neonatal bone development and adult bone remodeling involve regulation of vascular endothelial growth factor (VEGF). Journal of Bone and Mineral Research. 2012;27:586-595.
  15. McCauley LK, Martin TJ. Twenty-five years of PTHrP progress: from cancer hormone to multifunctional cytokine. J Bone Miner Res. 2012 Jun;27(6):1231-9.
  16. Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, Kikuchi Y, Takada I, Kato S, Kani S, Nishita M, Marumo K, Martin TJ, Minami Y, Takahashi N. Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat Med. 2012 Feb 19;18(3):405-12.
  17. Quach JM, Walker EC, Allan E, Solano M, Yokoyama A, Kato S, Sims NA, Gillespie MT, Martin TJ. Zinc finger protein 467 is a novel regulator of osteoblast and adipocyte commitment. J Biol Chem. 2011 Feb 11;286(6):4186-98.
  18. Winkler IG*, Sims NA*, Pettit AR*, Barbier V, Nowlan B, Helwani F, Poulton IJ, van Rooijen N, Alexander KA, Raggatt LJ, Lévesque J-P. Bone marrow macrophages are essential to hematopoietic stem cell (HSC) niches and their depletion mobilizes HSC. Blood. *, contributed equally. Dec 2;116(23):4815-28 (2010). ISI Highly Cited.
  19. Sims, N.A., Walsh, N.C. gp130 cytokines and bone remodeling in health and disease. BMB Reports. 2010 Aug;43(8):513-22.
  20. Gooi JH, Pompolo S, Karsdal M, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PWM, Walsh NC, Chia LY, Gillespie MT, Quinn JMW, Martin TJ & Sims NA. Calcitonin impairs the anabolic effect of PTH and stimulates sclerostin expression by osteocytes. Bone 46(6):1486-1497 (2010)
  21. 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. J Clin Invest. 2010 Feb 1;120(2):582-92
  22. 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.