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Bone Growth and Repair Research Group

Bone Growth and Repair Research GroupAn 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. 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 Associate 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.

PeoplePeople

UniSA staff
Associate Professor Cory Xian - group leader
Dr Tetyana Shandala - research fellow
Dr Blair Hopwood - research fellow
Michaela Scherer- research associate
Stan Flavel - research associate and lab manager

Postgraduate students
Rosa Chung
Chiaming Fan
Laura Fong
Maria Garcia
Kristen Georgiou
Tristan King
Carmen Macsai
Rethi Raghu Nadhanan


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: Tetyana Shandala, Blair Hopwood, Michaela Scherer, Laura Fong, Stan Flavel, 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: Blair Hopwood, Carmen Macsai, Rosa Chung, Stan Flavel, 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: Michaela Scherer, Chiaming Fan, Tristan King, Kristen Georgiou, Rethi Raghu Nadhanan, Maria Garcia, Stan Flavel, Bruce Foster, 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.


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

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, R Chung, CE Macsai, and BK Foster (2008). Injury responses and repair mechanisms at the injured growth plate cartilage of growing long bones. In Research Advances in Histochemistry and Cytochemistry (Global Research Network, in press)


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 us on:

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

 

 

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