Jump to Content

Bone Growth and Repair Research Group

Bone Growth and Repair Research Group An international leader in paediatric bone biology research, the Sansom Institute's Bone Growth and Repair Research Group (BGRRG) explores the mechanisms and regulation of children's bone growth, bone growth defects, growth plate and bone injury and repair, as well as the pathobiology and prevention of cancer chemotherapy-induced bone loss and marrow adiposity. The group's research is aimed at developing biological treatments that impact on children's bone growth, bone mass accumulation, and adult bone health.

Headed by NHMRC Senior Research Fellow Professor Cory Xian, the BGRRG was established in 2008 and expanded from the former Bone Growth Research Laboratory based at the Adelaide's Women's and Children's Hospital, South Australia.

Using in vivo, ex vivo and in vitro models and a wide range of histological, cellular and molecular techniques, the group's research activities can be classified into three areas: the mechanisms of bone growth, bone mass accumulation, and nutritional regulation; growth plate injury responses, repair mechanisms, and growth factor and/or stem cell-based regeneration; and pathophysiology for and prevention of cancer chemotherapy-induced bone growth defects and bone loss.

People

Bone Growth PicUniSA staff

Professor Cory Xian - group leader
Dr Fiona Zhou - NHMRC CJ Martin research fellow
Dr Rosa Chung - research fellow
Dr Alice Lee - research fellow
Dr Kristen Georgiou - research fellow
Dr Chiaming Fan - research fellow
Ms Tina Vincent - research associate

Postgraduate students

Laura Fong
Tristan King
Michelle Yu-Wen Su
Rethi Raghu Nadhanan
Long Nguyen
Carla Toop

Collaborators

The Bone Growth and Repair Research Group enjoys productive relationships with various collaborators, including:

Projects

Below is a brief description in broad terms of our current and recent research projects.

Mechanisms of bone growth, bone mass accumulation, and nutritional regulation
Researchers: Laura Fong, Long Nguyen, Bev Muhlhausler, Cory Xian
Funding: NHMRC, Bone Growth Foundation
We are interested in understanding the mechanisms for normal bone growth and bone lengthening, and bone mass accumulation. Our current focus is on understanding the growth plate biology, its molecular regulation, osteocyte biology and bone remodelling. We are also investigating whether some micro-nutrients can be used to positively modulate bone growth, bone mass accumulation, populations of skeletal stem cells, and prevention of age-related bone loss and osteoporosis.

Mechanisms for growth plate trauma injury-induced growth defects
Researchers: Rosa Chung, Fiona Zhou, Michelle Su, Bruce Foster, Cory Xian
Funding: NHMRC, Channel-7 Children's Research Foundation, Bone Growth Foundation
Growth plate trauma injury is a major problem as 20 per cent childhood bone fractures involve growth plate and the inured growth plate cartilage is often undesirably repaired by bony tissue leading to growth defects. Our group has been investigating mechanisms for the faulty repair and developing growth factor - and stem cell - based repair.

Mechanisms for and prevention of chemotherapy-induced growth defects
Researchers: Chiaming Fan, Tristan King, Kristen Georgiou, Alice Lee, Tina Vincent, Rethi Raghu Nadhanan, Cory Xian
Funding: NHMRC, Channel-7 Children's Research Foundation, Bone Growth Foundation
While chemotherapy-based cancer treatment is becoming more successful and thus intensified, chemotherapy-induced long-term side effects are becoming more obvious: it stunts bone growth and causes osteoporosis and frequent bone fractures which persist into adulthood. Our group is investigating the underlying cellular and molecular mechanisms for chemo-induced bone growth defects and the regeneration potentials of bone and bone marrow. We also aim to develop supplementary preventative treatment that will preserve bone growth during chemotherapy.

Pathophysiology for and prevention of breast cancer chemotherapy-induced bone loss
Researchers: Chiaming Fan, Kristen Georgiou, Rethi Raghu Nadhanan, Peter Howe, Ross McKinnon, Dorothy Keefe, Cory Xian
Funding: NHMRC
Combination cytotoxic chemotherapy is the current optimal approach for treating breast cancer in premenopausal women. However, long term skeletal defects (osteoporosis and fractures) caused by the chemotherapy have become an increasingly serious problem due to its intensified use and improved patient survival rate. This project seeks to elucidate the mechanisms for chemotherapy-induced bone defects and to initiate development of a preventative treatment using natural bioactive micronutrients.

 

Publications

Below is a list of selected research publications involving members of the Bone Growth and Repair Research Unit (UniSA researchers are indicated in bold):

Zhang J, Lou X, Xian CJ, Liu Z, Zhou X-F (2001). Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur. J. Neurosci. 12, 4171-4180.

Troyer KL, Luetteke NC, Saxon ML, Qiu TH, Xian CJ, & Lee DC (2001). Growth retardation, duodenal lesions and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin and TGF-alpha. Gastroenterology 121, 68-78.

Xian CJ, Li L, Deng YS, Zhou SP, & Zhou XF (2001). Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. Exp. Neurol. 172, 182-188.

Xian CJ, Cool J, Howarth GS, & Read LC (2002). Effects of TGF-a gene knock out on intestinal epithelial cell proliferation, migration, apoptosis, and mucosal recovery from methotrexate-induced damage. Journal of Cellular Physiology 191, 105-115.

Li L, Xian CJ, Zhong JH, Zhou X-F (2002). Effect of lumbar 5 ventral root transection on pain behaviors: a novel rat model for neuropathic pain without axotomy of primary sensory neurons. Exp. Neurol. 175, 23-34

Li L, Xian CJ, Zhong JH, Zhou XF (2003). Lumbar 5 ventral root transection induced upregulation of nerve growth factor in sensory neurons and their target tissues: a mechanism in neuropathic pain. Mol. Cell. Neurosci.23, 232-250.

Xian CJ, Zhou FH, McCarty RC, & Foster BK (2004). Intramembranous ossification mechanism for bone bridge formation at the growth plate cartilage injury site. J. Orthop. Res. 22, 417-426.

Xian CJ, Howarth GS, Cool JC, and Foster BK (2004). Effects of acute 5-fluorouracil chemotherapy and insulin-like growth factor-I pretreatment on growth plate cartilage and metaphyseal bone in rats. Bone 35, 739-749.

Zhou FH, Foster BK, Sander G, and Xian CJ (2004). Expression of inflammatory cytokines and growth factors at the injured growth plate of young rats. Bone 35, 1307-1315.

Zhou X-F, Li WP, Zhong JH, Mi JX, and Xian CJ (2005). Differential effects of endogenous BDNF on the survival of axotomized sensory neurons in dorsal root ganglia: a possible role for the p75 neurotrophin receptor. Neuroscience 132, 591-603

Xian CJ, JC Cool, T Pyragius, BK Foster (2006). Damage and recovery of the bone growth mechanism in young rats following 5-fluorouracil acute chemotherapy. Journal of Cellular Biochemistry 99, 1688-1704

Arasapam G, J Cool, M Scherer, BK Foster, CJ Xian (2006). Roles of iNOS and Cox-2 in the bony repair of the injured growth plate cartilage. Journal of Cellular Biochemistry 99, 450-461

Ngo T, M Scherer, FH Zhou, BK Foster, CJ Xian (2006). Expression of Bone Morphogenetic Proteins and Receptors at Injured Growth Plate Cartilage in Young Rats. J Histochem. Cytochem. 54, 845-854

Zhou FH, BK Foster, XF Zhou, CJ Xian (2006). TNF-alpha mediates p38 MAP kinase activation and negatively regulates bone formation at the growth plate injury site in rats. Journal of Bone and Mineral Research 21, 1075-1088

Chung R, J Cool, M Scherer, BK Foster, CJ Xian (2006). Roles of neutrophil-mediated inflammatory response in the bony repair of the injured growth plate cartilage in rats. J Leukocyte Biol 80, 1272-80

Xian CJ, JC Cool, J van Gangelan, BK Foster, GS Howarth (2007). Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and metaphyseal bone inrats. Cancer Biology & Therapy 6, 170-177

Xian CJ, JC Cool, MA Scherer, CE Macsai, CM Fan, M Covino, BK Foster (2007). Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects. Bone 41, 842-850

Xian CJ, JC Cool, MA Scherer, CM Fan, BK Foster (2008). Folinic acid attenuates methotrexate chemotherapy-induced damages on bone growth mechanisms and pools of bone marrow stromal cells. Journal Cellular Physiology 214, 777-785

Fan C, Cool JC, Scherer MA, Foster BK, Shandala T, Tapp H, Xian CJ (2009). Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment. Bone 44(1):61-70.

McCarty R.C., Gronthos S., Zannettino A.C.W., Foster B.K., Xian C.J (2009). Characterisation and Developmental Potential of Ovine Bone Marrow Derived Mesenchymal Stem Cells. Journal of Cellular Physiology 219: 324-33

Chung R, BK Foster, AC Zannettino, CJ Xian (2009). Potential roles of growth factor PDGF-BB in the bony repair of injured growth plate. Bone 44, 878-885

Gronthos S, RC McCarty, DMrozik, S Fitter, S Paton, D Menicanin, S Itescu, P M Bartold, CJ Xian, and AC Zannettino (2009). Heat Shock Protein-90 beta is Expressed at the Surface of Multipotential Mesenchymal Precursor Cells: Generation of a Novel Monoclonal Antibody, STRO-4, with Specificity for MPC from Human and Ovine Tissues. Stem Cells and Development 18:1253-62

Fong L, K Tan, C Tran, JC Cool, MA Scherer, R Elovaris, P Coyle, BK Foster, AM Rofe, and CJ Xian (2009). Interaction of dietary zinc and intracellular binding protein metallothionein in postnatal bone growth. Bone 44, 1151–1162

Li F, Li L, Song X-Y, Zhong J-H, Luo X-F, Xian CJ, and Zhou X-F (2009). Preconditioning selective ventral root injury promotes plasticity of ascending sensory neurons in the injured spinal cord of adult rats – possible roles of brain-derived neurotrophic factor, TrkB and p75 neurotrophin receptor. European Journal of Neuroscience 30, 1280–1296
 
McCarty RC, Xian CJ, Gronthos S, Zannettino ACW, and Foster BK (2010). Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury. The Open Orthopaedics Journal 4, 220-226

Tran CD, JC Cool, Xian CJ (2010). Dietary zinc and metallothionein on small intestinal disaccharidases activity in mice. World J Gastroenterol 17(3):354-360

Ma HP, Ming LG, Ge BF, Zhai YK, Song P, Xian CJ, Chen KM (2011). Icariin is more potent than genistein in promoting osteoblast differentiation and mineralisation in vitro. J Cell Biochem. 112:916-23

KR Georgiou, MA Scherer, CM Fan, JC Cool, TJ King, BK Foster and CJ Xian (2011). Methotrexate chemotherapy reduces osteogenesis but increases adipogenic potential in the bone marrow. J Cell Physiol (in press: doi: 10.1002/jcp.22807). [Epub ahead of print]

 

Review Articles and Book Chapters:

Xian CJ (2003). Roles of growth factors in chemotherapy-induced intestinal mucosal damage repair. Current Pharmaceutical Biotechnology 4, 260-269 (Invited review)

Xian CJ & Zhou XF (2004). EGF family of growth factors: essential roles and functional redundancy in the nerve system. Frontiers in Bioscience 9, 85-92 (Invited review)

Xian CJ and BK Foster (2006). Repair of injured articular and growth plate cartilage using mesenchymal stem cells and chondrogenic gene therapy. Current Stem Cell Research and Therapy 1, 213-229 (Invited review)

Xian CJ and Foster BK. (2006). The biological aspects of children's fractures. In: Fractures in Children. (6th edition). Eds: Beaty J and Kasser J. Lippincott Williams and Wilkins, Philadelphia. Pages 21-50 (Invited book chapter)

Xian CJ (2007). Roles of epidermal growth factor family in the regulation of postnatal somatic growth. Endocrine Reviews 28, 284-296

Macsai CE, BK Foster, CJ Xian (2008). Roles of Wnt signalling in bone growth, remodelling, skeletal disorders and fracture repair. Journal of Cellular Physiology 215, 578-587

Xian CJ and Zhou X-F (2009). Treating skeletal pain: limitations of conventional anti-inflammatory drugs and anti-neurotrophic factor as a possible alternative. Nature Reviews Rheumatology 5, 92-98. (Invited review)

Georgiou KR, Foster BK, Xian CJ (2010). Damage and Recovery of the Bone Marrow Microenvironment Induced by Cancer Chemotherapy - Potential Regulatory Role of Chemokine CXCL12/Receptor CXCR4 Signalling. Current Molecular Medicine 10:440-53

Xian CJ (2010). Mechanisms of bony repair at the injured growth plate cartilage. In Bone Regeneration: Growth Factors, Augmentation Procedures and Tissue Engineering Applications. Nova Science Publishers, Inc, Hauppauge, NY 11788. Pages 263-273. ISBN 978-1-60876-621-5 (Invited book chapter).

Xian CJ and T Shandala (2010). Roles of EGF family of growth factors in growth. In: VR Preedy (ed) The Handbook of Growth and Growth Monitoring in Health and Disease. Springer (Invited chapter, in press).

Chung R, Foster BK, Xian CJ (2010). Injury responses and repair mechanisms at injured growth plate. Frontiers in Bioscience (Schol Ed) 2011 Jan 1;3:117-125 (invited review)

Fan CM, Georgiou KR, King TJ, Xian CJ (2011). Methotrexate toxicity in growing long bones of young rats: a model for studying cancer chemotherapy-induced bone growth defects in children. Journal of Biomedicine and Biotechnology (doi:10.1155/2011/903097)

Fan CM, Foster BK, Wallace WH and Xian CJ (2011). Pathobiology and prevention of cancer chemotherapy-induced bone growth arrest, bone loss and osteonecrosis. Current Molecular Medicine 11:140-51

Contact

The Bone Growth and Repair Research Group is situated in the Reid Building, Sansom Institute, at the University of South Australia's City East campus in Adelaide.

For more information about the group and its activities, please contact:

Professor Cory Xian
Phone: +61 8 8302 1944
Fax: +61 8 8302 1087
Email: cory.xian@unisa.edu.au  

 

top^