Dr Liza Raggatt

Honorary Fellow

Mater Research Institute-UQ
Faculty of Medicine

Overview

Delineation of osteal macrophage function in the bone microenvironment: dual roles in bone dynamics and stem cell niches.

Bone and joint diseases are a national and international health and research priority costing the Australian health system over $10 billion annually. The bony skeleton is a dynamic metabolically active tissue that is continuously remodelled and repaired to maintain calcium homeostasis and structural integrity. The microenvironment at the inner surface of long bones (endosteum), including the bone matrix and associated bone lining cells, is crucial to the dynamic processes of bone modelling and remodelling. I have recently characterized 'osteomacs' as a resident tissue macrophage population within bone lining tissues and have shown that they promote bone mineralization in vitro and are necessary for the maintenance of bone forming osteoblasts in vivo. Thus osteomacs are cellular constituents of endosteal niches and play an osteoblast-support function in this microenvironment. We are investigating the unique phenotype and expression profile (mRNA and protein) of osteomacs in order to fully delineate their functional potential in bone dynamics.

Recently it has been shown that the endosteal environment is also essential for the maintenance of mesenchymal stem cell (MSC) and haematopoietic stem cell (HSC) niches. Osteoblasts need to be present on the bone surface to ensure HSC maintenance in the endosteal niche. Therefore we hypothesised that osteomacs, as a consequence of their presence in the niche and osteoblast support-function, contribute both indirectly and directly to the generation of this stem cell nursery. We have shown that loss of osteomacs and subsequently osteoblasts occurs during G-CSF induced HSC mobilization. Importantly, in vivo depletion of osteomacs (using transgenic Mafia mice) also causes marked egress of HSC from bone marrow into the blood and spleen. These data provide compelling support that osteomacs are required for maintenance of osteoblast bone forming surfaces and provide caretaker support for the endosteal stem cell niches.

My research team has a number of projects that aim to understand the cellular architecture of the endosteal stem cell niches and the role of osteomacs in this environment. This is an essential step toward enhancing clinical HSC mobilization options in order to improve bone marrow transplantation outcomes in multiple myeloma and lymphoma and also ensuring that the promise of MSC therapy is translated into a clinical reality.

Qualifications

  • PhD, The University of Adelaide

Publications

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Supervision

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Available Projects

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Publications

Journal Article

Conference Publication

  • Levesque, Jean-Pierre, Kaur, Simranpreet, Jacobsen, Rebecca, Millard, Susan, Batoon, Lena, Winkler, Ingrid, Macdonald, Kelli, Perkins, Andrew, Hume, David, Raggatt, Liza and Pettit, Allison (2016). Radio-resistant recipient bone marrow (BM) macrophages (Macs) are necessary for hematopoietic stem cell (HSC) engraftment post transplantation. In: 45th Annual Scientific Meeting of the ISEH – International Society for Experimental Hematology. 45th Annual Scientific Meeting of the ISEH – International Society for Experimental Hematology, San Diego, CA, United States, (S43-S44). 25-28 August, 2016. doi:10.1016/j.exphem.2016.06.049

  • Kaur, S., Raggatt, L. J., Jacobsen, R. N., Millard, S., Batoon, L., Winkler, I. G., Macdonald, K. P. A., Perkins, A. C., Hume, D. A., Levesque, J. P. and Pettit, A. R. (2016). Recipient bone marrow (BM) macrophages (Macs) are vital for haematopoietic stem cell (HSC) engraftment post autologous transplantation. In: International Congress of Immunology (ICI), Melbourne, VIC, Australia, (762-762). 21-26 August 2016. doi:10.1002/eji.201670200

  • Pettit, A, Raggatt, L, Wullschleger, M, Alexander, K, Steck, R, Kaur, S and Wu, A (2013). Fracture Healing Via Periosteal Callus Formation Requires Macrophages for Both Initiation and Progression of Endochondral Ossification. In: Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Baltimore MD, (). OCT 04-07, 2013.

  • Jacobsen, Rebecca, Pettit, Allison, Barbier, Valerie, Nowlan, Bianca, Raggatt, Liza, Winkler, Ingrid and Levesque, Jean-Pierre (2013). Mobilising Doses of G-Csf Stop Medullary Erythropoiesis by Depleting Cd169+Macrophages. In: 42nd Annual Scientific Meeting of ISEH - Society for Hematology and Stem Cells — Abstracts. 42nd Annual Scientific Meeting of ISEH - Society for Hematology and Stem Cells, Vienna, Austria, (S59-S59). 22-25 August 2013. doi:10.1016/j.exphem.2013.05.230

  • Jacobsen, Rebecca, Pettit, Allison R., Raggatt, Liza J., Nowlan, Bianca, Barbier, Valerie, Forristal, Catherine E., Winkler, Ingrid G. and Levesque, Jean-Pierre (2013). Mobilizing Doses Of G-CSF Stop Medullary Erythropoiesis By Depleting F4/8o+VCAM1+ER-HR3+CD169+Erythroid-Island Macrophages. In: Blood. 55th Annual Meeting of the American-Society-of-Hematology, New Orleans, LA, United States, (). 7-10 December 2013.

  • Pettit, A. R., Kaur, S., Alexander, K. A., MacDonald, K. P. A. and Raggatt, L. J. (2011). B Cells Do Not Influence Intramembranous Bone Modelling in Vivo. In: Osteoporosis International. IOF Regionals 2nd Asia-Pacific Osteoporosis and Bone Meeting / ANZBMS Annual Scientific Meeting held with the JSBMR, Gold Coast Australia, (S537-S538). Sep 04-08, 2011.

  • Levesque, Jean-Pierre, Bendall, Linda J., Pettit, Allison R., Raggatt, Liza, Jacobsen, Rebecca, Barbier, Valarie, Nowlan, Bianca, Shen, Yi Shen, Sims, Natalie A. and Winkler, Ingrid G. (2011). Mobilizing agents G-CSF, cyclophosphamide or AMD3100 (Plerixafor) Have distinct effects on osteoblasts, hematopoietic stem cell niches, and B-Lymphopoiesis. In: Abstracts of the American Society of Hematology 53rd Annual Meeting. 53rd Annual Meeting and Exposition of the American Society of Hematology (ASH), San Diego CA, United States, (1713-1713). 10-13 December 2011.

  • Jacobsen, RN, Levesque, JP, Barbier, V, Raggatt, LJ and Pettit, AR (2010). DEPLETION OF BONE MARROW PHAGOCYTES CAUSES THE MOBILIZATION OF LONG-TERM RECONSTITUTING HEMATOPOIETIC STEM CELLS. In: EXPERIMENTAL HEMATOLOGY. 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells, Melbourne AUSTRALIA, (S93-S94). SEP 15-18, 2010.

  • Levesque, J. P., Raggatt, L. J., Pettit, A. R., Sims, N. A., Bendall, L. J. and Helwani, F. (2009). Endosteal Macrophages Maintain the Hematopoietic Stem Cell (Hsc) Niche and Participate in Hsc Mobilization Induced by G-Csf or Chemotherapy. In: Experimental Hematology. 38th Annual Scientific Meeting of the ISEH Society for Hematology and Stem Cells, Athens, Greece, (S31-S31). 9-12 September 2009.

  • Alexander, K. A., Raggatt, L., Chang, M., Maylin, E., Muller, R., Kohler, T., Wu, A., Hume, D. and Pettit, A. (2009). Osteomacs are Critical for Optimal Intramembranous Bone Formation in a Tibial Defect Model of Bone Healing. In: Journal of Bone and Mineral Research. Australian Society of Bone and Mineral Research (ASBMR) 31st Annual Meeting, Denver, Colorado, USA, (). 11-15 September, 2009.

  • Alexander, K. A., Raggatt, L. J., Chang, M. K., Maylin, E. R., Muller, R., Kohler, T., Wu, A. C. K., Hume, D. A. and Pettit, A. R. (2009). Osteomacs are critical for optimal intramembranous bone formation in a tibial defect model of bone healing. In: Bone. Abstracts from the 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society. 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society, Sydney, NSW, Australia, (S30-S30). 21-25 March 2009. doi:10.1016/j.bone.2009.01.076

  • Pettit, A. R., Sims, N. A., Winkler, I. G., Alexander, K. A., Helwani, F., Raggatt, L. J. and Levesque, J. P. (2009). Osteomacs maintain the endosteal hematopoietic stem cell niche and participate in mobilization. In: Bone. Abstracts from the 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society. 2nd Joint Meeting of the International Bone and Mineral Society/Australian New Zealand Bone and Mineral Society, Sydney, Australia, (S32-S33). 21-25 March, 2009. doi:10.1016/j.bone.2009.01.082

  • Raggatt, L., Chang, M., Alexander, K., Maylin, E., Walsh, N., Gravallese, E., Hume, D. and Pettit, A. (2009). Osteomacs: Osteoclast Precursors During Inflammatory Bone Disease but Regulators of Physiologic Bone Remodeling. In: Journal of Bone and Mineral Research. Australian Society of Bone and Mineral Research (ASBMR) 31st Annual Meeting, Denver, Colorado, USA, (). 11-15 September, 2009.

  • Raggatt, L. J., Chang, M. K., Alexander, K. A., Maylin, E. R., Walsh, N. C., Gravallese, E. M., Hume, D. A. and Pettit, A. R. (2009). Osteomacs: osteoclast precursors during inflammatory bone disease but regulators of physiologic bone remodelling. In: Bone. Abstracts from the 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society. 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society, Sydney, Australia, (S136-S137). 21-25 March, 2009. doi:10.1016/j.bone.2009.01.300

  • Chang, M. K., Pettit, A. R., Schroder, K., Ripoll, V. M., Alexander, K. A., Hume, D. A. and Raggatt, L. (2008). Primary murine osteoblast cultures contain macrophages that enhance osteoblast mineralisation. In: Abstracts of the 35th European Symposium on Calcified Tissues. ECTS 35th European Symposium on Calcified Tissues, Barcelona, Spain, (S98-S99). 24-28 May 2008. doi:10.1007/s00223-008-9118-5

  • Alexander, K. A., Chang, M. K., Hume, D. A., Pettit, A. R., Raggatt, L., Ripoli, V. M. and Schroder, K. (2008). Primary murine osteoblast cultures contain macrophages that enhance osteoblast mineralization. In: Calcified Tissue International. 35th European Symposium on Calcified Tissues, Barcelona, Spain, (S98-S99). 24-28 May 2008. doi:10.1007/s00223-008-9118-5

  • Raggatt, L. J., Chang, M. K., Alexander, K. A., Kuiliwaba, J. S., Fazzalari, N. L., Hume, D. A. and Pettit, A. R. (2007). Osteal Macrophages: Novel regulators of Bone Formation. In: Journal of Bone and Mineral Research: 29th Annual Meeting of the American Society for Bone and Mineral Research. 29th Annual Meeting of the American Society for Bone and Mineral Research, Honolulu, HI, (s53-s53). 16th -19th September, 2007.

  • Raggatt, L. J., Alexander, K. A., Kuliwaba, J. S., Fazzalari, N. L., Hume, D. A. and Pettit, A. R. (2007). Osteal macrophages: Novel regulators of bone formation. In: Journal of Bone and Mineral Research. 29th Annual Meeting of the American Society for Bone and Mineral Research, Honolulu, HI, United States, (S53-S53). 16-19 September 2007.

  • Chang, M., Hume, D. A., Pettit, A. R., Raggatt, L., Ripoll, V. M. and Schroder, K. (2007). Primary Murine Osteoblast Cultures Contain Macrophages that Enhance Osteoblast Mineralisation. In: Journal of Bone and Mineral Research. 29th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR), Honolulu, Hawaii, USA, (S139-S139). 16th - 19th September, 2007.

  • Pettit, A. R., Chang, M. K., Alexander, K. A., Wu, A. C., Hume, D. A. and Raggatt, L. J. (2007). The endosteal bone niche contains macrophages that regulate osteoblast function. In: Bone. 17th Scientific Meeting of the International Bone & Mineral Society, Montreal, Canada, (S127-S127). 24-29 June 2007. doi:10.1016/j.bone.2007.04.166

  • Grondahl, L, Keen, I, Raggatt, L, Chandler-Temple, A. F., Cool, S M and Trau, M (2006). Tailoring poly(3-hydroxybutyrate-co-3-hydroxyvalerate) for bone tissue engineering. In: 28th Australasian Polymer Symposium & Aust Society for Biomaterials. 28th Australasian Polymer Symposium & Aust Society for Biomat, Rotorua, (Abstract). 5-9 Feb, 2006.

  • Raggatt, LJ, Qin, L, Cool, S, Nurcombe, V and Partridge, N (2005). Parathyroid hormone stimulation of syndecan-4 in osteoblastic cells.. In: Journal of Bone and Mineral Research. 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Nashville Tn, (S429-S429). Sep 23-27, 2005.

  • Raggatt, J. L., Qin, L., Cool, S. M., Nurcombe, V. and Partridge, N. C. (2005). Parathyroid hormone regulation of syndecan-4 in osteoblast cells. In: Journal of Bone and Mineral Research. 27th Annual Meeting of the American Society for Bone and Mineral Research, Nashville, Tennessee, U.S., (S429-S429). 23-27 September 2005.

  • Raggatt, J. L., Qin, L., Cool, S. M., Nurcombe, V. and Partridge N. C. (2005). Parathyroid hormone stimulation of Syndecan-4 in osteoblastic cells. In: Journal of Bone and Mineral Research. 27th Annual Meeting of the American Society for Bone and Mineral Research, Nashville, Tennessee, U.S., (). 24-26 September, 2005.

  • Keen, I., Raggatt, L., Cool, S. M., Nurcombe, V., Fredericks, P., Trau, M. and Grondahl, L. (2005). Response of osteoblast cells to the surface properties of Poly(3-hydroxybutyrate-co-hydroxyvalerate) PHBV. In: 2nd ARC Centre For Functional Nanomaterials Annual Conference. 2nd ARC Centre For Functional Nanomaterials Annual Conference, Maroochydore, (Seminar). Nov, 2005.

  • Qin, L., Tamasi, J., Raggatt, L., Li, X., Feyen, J., Lee, D., DiCicco-Bloom, E. and Partridge, N. C. (2004). Amphiregulin is a novel growth factor in bone stimulated by parathyroid hormone and required for normal bone development. In: FASEB Journal. Annual Meeting of the American Society for Biochemistry-and-Molecular-Biology/8th Congress of the International Union for Biochemistry and Molecular Biology, Boston, MA, USA, (C299-C299). 12-16 June 2004.

  • Keen, I., Grondahl, L., Raggatt, L., Fredericks, P.M., Nurcombe, V., Trau, M. and Cool, S. M. (2004). Influence of solvent on the surface properties of PHBV solvent cast films. In: 27th Australasian Polymer Symposium. 27th Australasian Polymer Symposium, Adelaide, (Abstract). Nov, 2004.

  • Qin, L, Raggatt, L, Li, X, Tamasi, J, Feyen, JHM and Partridge, NC (2003). Amphiregulin: A possible mediator of parathyroid hormone's anabolic actions in bone.. In: Journal of Bone and Mineral Research. 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Minneapolis Minnesota, (S100-S100). Sep 19-23, 2003.

  • Raggatt, LJ, Qin, L and Partridge, NC (2003). Parathyroid hormone stimulation of IL-18 in osteoblastic cells.. In: Journal of Bone and Mineral Research. 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Minneapolis Minnesota, (S398-S398). Sep 19-23, 2003.

  • Qin, Ling, Raggatt, L., Li, X., Tamasi, J., Feyen, J. H. M. and Partridge, N. C. (2003). Amphiregulin: A possible mediator of parathyroid hormone's anabolic actions in bone. In: Journal of Bone and Mineral Research: 25th Annual Meeting of the American Society for Bone and Mineral Research. 25th Annual Meeting of the American Society for Bone and Mineral Research, Minneapolis, Minnesota, U.S.A., (S100-S100). 19-23 September, 2003.

  • Choudhury, I., Williams, S., Raggatt, L. J, Byrne, M. H., Krane, S. M. and Partridge, N. C. (2003). Interaction of Collagenase-3 with its Specific Receptor and LRP-1. In: The FASEB Journal: Experimental Biology 2003 Meeting. Experimental Biology 2003 Meeting, San Diego, California, USA, (A998-A999). 11th - 15th April, 2003.

  • Raggatt, Liza Jane, Qin, Ling and Partridge, Nicola (2003). Parathyroid hormone stimulation of IL-18 gene expression in osteoblasts. In: Vincent T. Marchesi, FASEB Journal. Experimental Biology 2003: Meeting Abstracts. AAA Annual Meeting at Experimental Biology 2003, San Diego, CA, U.S.A., (A188-A189). 11-15 April 2003.

  • Raggatt, L. J., Qin, L. and Partridge, N. C. (2003). Parathyroid hormone stimulation of IL-18 in osteoblastic cells. In: Journal of Bone and Mineral Research. 25th Annual Meeting of the American Society for Bone and Mineral Research, Minneapolis, U.S., (S398-S398). 19-23 September, 2003.

  • Raggatt, LJ, Choudhury, I, Williams, S, Tiku, ML and Partridge, NC (2002). Characterization of collagenase-3 binding and internalization by rabbit chondrocytes.. In: Journal of Bone and Mineral Research. 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, San Antonio Texas, (S223-S223). Sep 20-24, 2002.

  • Choudhury, I, Williams, S, Raggatt, LJ, Byrne, MH, Krane, SM and Partridge, NC (2002). Characterization of collagenase-3 binding to the collagenase-3 specific receptor and LRP1.. In: Journal of Bone and Mineral Research. 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, San Antonio Texas, (S171-S171). Sep 20-24, 2002.

  • Raggatt, L. J., Choudhury, I., Williams, S., Tiku ,M. L. and Partridge, N. C. (2002). Characterization of Collagenase-3 Binding and Internalization by Rabbit Chondrocytes. In: Journal of Bone and Mineral Research: 24th Annual Meeting of the American Society for Bone and Mineral Research. 24th Annual Meeting of the American Society for Bone and Mineral Research, San Antonio, Texas, USA, (S223-S223). 20th - 24th September, 2002.

  • Choudhury, I., Williams, S., Raggatt, L. J., Byrne, M. H., Krane, S. M. and Partridge, N. C (2002). Characterization of Collagenase-3 Binding to the Collagenase-3 Specific Receptor and LRP1. In: Journal of Bone and Mineral Research: 24th Annual Meeting of the American Society for Bone and Mineral Research. 24th Annual Meeting of the American Society for Bone and Mineral Research, San Antonio, Texas, USA, (S198-S198). 20th - 24th September, 2002.

  • Raggatt, LJ, Evdokiou, A and Findlay, DM (1999). Activation of the insert negative human calcitonin receptor: Phosphorylation of MAP kinase and inhibition of cellular proliferation.. In: Journal of Bone and Mineral Research. , , (S319-S319). .

  • Evdokiou, A, Raggatt, L, Atkins, GJ and Findlay, DM (1998). Growth inhibition by calcitonin of HEK293 cells is accompanied by induction of p21/WAF1/CIP1 and G2/M arrest. In: Molecular Biology of the Cell. , , (484A-484A). .

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.