Professor Christopher Little

Director Raymond Purves Bone and Joint Research Labs
Surgery, Northern Clinical School
Kolling Institute of Medical Research

E25 - Royal North Shore Hospital
The University of Sydney
NSW 2006 Australia

T: 02 9926 4800
F: 02 9926 5266
E:

Curriculum vitae

Biographical details

Professor Christopher Little is director of the Raymond Purves Bone and Joint Research Labs at the Kolling Institute of Medical Research at Royal North Shore Hospital, Australia. Chris is a qualified Veterinarian with specialist surgery training and ACVS certification. He was awarded a PhD degree from the University of Sydney in 1996 for his studies of cartilage degradation in a sheep model of osteoarthritis (OA). Following a 5-year postdoctoral position at Cardiff University (UK), he was awarded an Arthritis Foundation of Australia Fellowship at the University of Melbourne. In 2004 he moved to his current position in the University of Sydney Faculty of Medicine. Chris’s research interests focus on defining the biochemical and molecular mechanisms of joint pathology in OA, and tendon and intervertebral disc degeneration, and are based on the belief that it is only though a better understanding the mechanisms that drive the initiation and progression of these diseases that new therapies can be developed. Chris is recognized internationally for his expertise in the development and use of animal models of bone and joint disease. He has served as an Associate Editor of Osteoarthritis and Cartilage, and a leader of the OARSI international initiative to establish standardised methods for evaluation of animal models of OA. Chris received the 2010 Barry Preston Award from the Matrix Biology Society of Australia and New Zealand, presented to an outstanding leader in the field. He has authored/co-authored 104 scientific papers and 7 book chapters.

Current national competitive grants*

2013

Synovial macrophages and T-cells are therapeutic targets in osteoarthritis
Little C, Hunter D
NHMRC Project Grant ($632,127 over 3 years)

2012

Nano-mechanical and nano-structural investigation of dentine: unravelling a novel nano-scale regulator of high durability of mineralised tissues.
Swain M, Little C
ARC Discovery Projects ($370,000 over 3 years)

The calcium channel TRPV4 in skeletal development and arthritis
Little C, McIntyre P
NHMRC Project Grant ($96,000 over 3 years)

Sclerostin Is A Key Regulator Of Wnt Signalling In Bone And Cartilage Pathology In Osteoarthritis
Little C, Sambrook P
NHMRC Project Grants ($571,010 over 3 years)

* Grants administered through the University of Sydney

Publications

2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008

2014

   
  • El-Hoss, J., Kolind, M., Jackson, M., Deo, N., Mikulec, K., McDonald, M., Little, C., Little, D., Schindeler, A. (2014), Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib). Bone. 59C, 151-161. [Abstract]
  • Hodges, P., James, G., Blomster, L., Hall, L., Schmid, A., Shu, C., Little, C., Melrose, J. (2014), Can Pro-Inflammatory Cytokine Gene Expression Explain Multifidus Muscle Fiber Changes After an Intervertebral Disc Lesion?. Spine. 39(13), 1010-1017. [Abstract]
  • Jackson, M., Moradi, B., Smith, M., Jackson, C., Little, C. (2014), Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 are activated by Activated Protein C (APC) in human osteoarthritic cartilage chondrocytes. Arthritis & Rheumatology. 66(6), 1525¿1536. [Abstract]
  • Xue, M., Shen, K., McKelvey, K., Li, J., Chan, Y., Hatzis, V., March, L., Little, C., Tonkin, M., Jackson, C. (2014), Endothelial protein C receptor associated invasiveness of rheumatoid synovial fibroblasts is likely driven by group V secretory phospholipase A2. Arthritis Research & Therapy. 16(1), R44. [Abstract]
  • Riordan, E., Little, C., Hunter, D. (2014), Pathogenesis of post-traumatic OA with a view to intervention. Best Practice & Research: Clinical Rheumatology. 28(1), 17-30. [Abstract]
  • Smith, R., McIlwraith, W., Schweitzer, R., Kadler, K., Cook, J., Caterson, B., Dakin, S., Heinegård, D., Screen, H., Stover, S., Crevier-Denoix, N., Clegg, P., Collins, M., Little, C., Frisbie, D., Kjaer, M., van Weeren, R., Werpy, N., Denoix, J., Carr, A., Goldberg, A., Bramlage, L., Smith, M., Nixon, A. (2014), Advances in the understanding of tendinopathies: a report on the Second Havemeyer Workshop on equine tendon disease. Equine Veterinary Journal. 46(1), 4-9. [Abstract]

2013

   
  • Melrose, J., Smith, M., Smith, S., Ravi, V., Young, A., Dart, A., Sonnabend, D., Little, C. (2013), Altered stress induced by partial transection of the infraspinatus tendon leads to perlecan (HSPG2) accumulation in an ovine model of tendinopathy. Tissue & Cell. 45(1), 77-82. [Abstract]
  • Malfait, A., Little, C., McDougall, J. (2013), A commentary on modelling osteoarthritis pain in small animals. Osteoarthritis and Cartilage. 21(9), 1316-1326. [Abstract]
  • Gossan, N., Zeef, L., Hensman, J., Hughes, A., Bateman, J., Rowley, L., Little, C., Piggins, H., Rattray, M., Boot-Handford, R., Meng, Q. (2013), The circadian clock in murine chondrocytes regulates genes controlling key aspects of cartilage homeostasis. Arthritis and Rheumatism. 65(9), 2334-2345. [Abstract]
  • Smith, M., Russell, A., Schiavinato, A., Little, C. (2013), A hexadecylamide - derivative of hyaluronan (HYMOVIS(R)) has superior beneficial effects on human osteoarthritic chondrocytes and synoviocytes than unmodified hyaluronan. Journal of Inflammation. 10(1), 26. [Abstract]
  • Shu, C., Hughes, C., Smith, S., Smith, M., Hayes, A., Caterson, B., Little, C., Melrose, J. (2013), The ovine newborn and human foetal intervertebral disc contain perlecan and aggrecan variably substituted with native 7D4 CS sulphation motif: spatiotemporal immunolocalisation and co-distribution with Notch-1 in the human foetal disc. Glycoconjugate Journal. 30(7), 717-725. [Abstract]
  • Smith, M., Jacobson, E., Dart, A., Little, C. (2013), Large proteoglycan metabolism in tendinopathy. British Journal of Sports Medicine. 47(9), e2. [Abstract]
  • Smith, M., Ravi, V., Dart, A., Sonnabend, D., Little, C. (2013), Factors affecting tendinopathogenesis. British Journal of Sports Medicine. 47(9), e2. [Abstract]
  • Bateman, J., Rowley, L., Belluoccio, D., Chan, B., Bell, K., Fosang, A., Little, C. (2013), Transcriptomics of Wild-Type Mice and Mice Lacking ADAMTS-5 Activity Identifies Genes Involved in Osteoarthritis Initiation and Cartilage Destruction. Arthritis and Rheumatism. 65(6), 1547-1560. [Abstract]
  • Little, C., Hunter, D. (2013), Post-traumatic osteoarthritis: from mouse models to clinical trials. Nature Reviews Rheumatology. 9(8), 485-497. [Abstract]
  • Shu, C., Smith, S., Little, C., Melrose, J. (2013), Comparative immunolocalisation of perlecan, heparan sulphate, fibroblast growth factor-18, and fibroblast growth factor receptor-3 and their prospective roles in chondrogenic and osteogenic development of the human foetal spine. European Spine Journal. 22(8), 1774-1784. [Abstract]
  • Cake, M., Read, R., Corfield, G., Daniel, A., Burkhardt, D., Smith, M., Little, C. (2013), Comparison of gait and pathology outcomes of three meniscal procedures for induction of knee osteoarthritis in sheep. Osteoarthritis and Cartilage. 21(1), 226-236. [Abstract]
  • Belluoccio, D., Rowley, L., Little, C., Bateman, J. (2013), Maintaining mRNA integrity during decalcification of mineralized tissues. PloS One. 8(3), e58154. [Abstract]

2012

   
  • Maher, A., Coles, C., White, J., Bateman, J., Fuller, E., Burkhardt, D., Little, C., Cake, M., Read, R., McDonagh, M., Rochfort, S. (2012), 1H NMR spectroscopy of serum reveals unique metabolic fingerprints associated with subtypes of surgically induced osteoarthritis in sheep. Journal of Proteome Research. 11(8), 4261-4268. [Abstract]
  • Chan, B., Little, C. (2012), The interaction of canonical bone morphogenetic protein- and Wnt-signaling pathways may play an important role in regulating cartilage degradation in osteoarthritis. Arthritis Research & Therapy. 14(3), 119. [Abstract]
  • Melrose, J., Isaacs, M., Smith, S., Hughes, C., Little, C., Caterson, B., Hayes, A. (2012), Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochemistry and Cell Biology. 138(3), 461-475. [Abstract]
  • Little, C., Zaki, S. (2012), What constitutes an "animal model of osteoarthritis"--the need for consensus?. Osteoarthritis and Cartilage. 20(4), 261-267. [Abstract]
  • Melrose, J., Shu, C., Young, C., Ho, R., Smith, M., Young, A., Smith, S., Gooden, B., Dart, A., Podadera, J., Appleyard, R., Little, C. (2012), Mechanical destabilization induced by controlled annular incision of the intervertebral disc dysregulates metalloproteinase expression and induces disc degeneration. Spine. 37(1), 18-25. [Abstract]
  • Fuller, E., Smith, M., Little, C., Melrose, J. (2012), Zonal differences in meniscus matrix turnover and cytokine response. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 20(1), 49-59. [Abstract]
  • Boeuf, S., Graf, F., Fischer, J., Moradi, B., Little, C., Richter, W. (2012), Regulation of aggrecanases from the ADAMTS family and aggrecan neoepitope formation during in vitro chondrogenesis of human mesenchymal stem cells. European Cells & Materials. 23, 320-332. [Abstract]

2011

   
  • Stanton, H., Melrose, J., Little, C., Fosang, A. (2011), Proteoglycan degradation by the ADAMTS family of proteinases. Biochimica et Biophysica Acta. 1812(12), 1616-1629. [Abstract]
  • Lamandé, S., Yuan, Y., Gresshoff, I., Rowley, L., Belluoccio, D., Kaluarachchi, K., Little, C., Botzenhart, E., Zerres, K., Amor, D., Cole, W., Savarirayan, R., McIntyre, P., Bateman, J. (2011), Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nature Genetics. 43(11), 1142-1146. [Abstract]
  • Bernardo, B., Belluoccio, D., Rowley, L., Little, C., Hansen, U., Bateman, J. (2011), Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis. The Journal of Biological Chemistry. 286(43), 37758-37767. [Abstract]
  • Glasson, S., Little, C. (2011), The recent paper "Multimodal imaging demonstrates concomitant changes in bone and cartilage after destabilization of the medial meniscus and increased joint laxity". Osteoarthritis and Cartilage. , 1076-1077. [Abstract]
  • Chan, B., Fuller, E., Russell, A., Smith, S., Smith, M., Jackson, M., Cake, M., Read, R., Bateman, J., Sambrook, P., Little, C. (2011), Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthritis and Cartilage. 19(7), 874-885. [Abstract]
  • Stanton, H., Golub, S., Rogerson, F., Last, K., Little, C., Fosang, A. (2011), Investigating ADAMTS-mediated aggrecanolysis in mouse cartilage. Nature Protocols. 6(3), 388-404. [Abstract]

2010

   
  • Schollum, M., Appleyard, R., Little, C., Melrose, J. (2010), A Detailed Microscopic Examination of Alterations in Normal Anular Structure Induced by Mechanical Destabilization in an Ovine Model of Disc Degeneration. Spine. 35(22), 1965-1973. [Abstract]
  • Glasson, S., Chambers, M., Van Den Berg, W., Little, C. (2010), The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 18 Suppl 3, S17-23. [Abstract]
  • Little, C., Smith, M., Cake, M., Read, R., Murphy, M., Barry, F. (2010), The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in sheep and goats. Osteoarthritis and Cartilage. 18(Suppl 3), S80-S92. [Abstract]
  • Melrose, J., Little, C. (2010), Immunolocalization of lymphatic vessels in human fetal knee joint tissues. Connective tissue research. 51(4), 289-305. [Abstract]
  • Nguyen, T., Little, C., Yenson, V., Jackson, C., McCracken, S., Warning, J., Stevens, V., Gallery, E., Morris, J. (2010), Anti-IgD antibody attenuates collagen-induced arthritis by selectively depleting mature B-cells and promoting immune tolerance. Journal of autoimmunity. 35(1), 86-97. [Abstract]
  • Little, C., Fosang, A. (2010), Is cartilage matrix breakdown an appropriate therapeutic target in osteoarthritis--insights from studies of aggrecan and collagen proteolysis?. Current Drug Targets. 11(5), 561-575. [Abstract]
  • Zreiqat, H., Belluoccio, D., Smith, M., Wilson, R., Rowley, L., Jones, K., Ramaswamy, Y., Vogl, T., Roth, J., Bateman, J., Little, C. (2010), S100A8 and S100A9 in experimental osteoarthritis. Arthritis research & therapy. 12(1), R16. [Abstract]
  • Little, C., Kim, Y. (2010), Targeting Cartilage Breakdown in Osteoarthritis. Journal of American Academy of Orthopaedic Surgeons. 18(4), 243-246.
  • Fosang, A., Last, K., Stanton, H., Golub, S., Little, C., Brown, L., Jackson, D. (2010), Neoepitope antibodies against MMP-cleaved and aggrecanase-cleaved aggrecan. Methods in molecular biology (Clifton, N.J.). 622, 312-47. [Abstract]

2009

   
  • Little, C., Barai, A., Burkhardt, D., Smith, S., Fosang, A., Werb, Z., Shah, M., Thompson, E. (2009), Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis and rheumatism. 60(12), 3723-33. [Abstract]
  • Smith, S., Whitelock, J., Iozzo, R., Little, C., Melrose, J. (2009), Topographical variation in the distributions of versican, aggrecan and perlecan in the foetal human spine reflects their diverse functional roles in spinal development. Histochemistry and Cell Biology. 132(5), 491-503. [Abstract]
  • Melrose, J., Burkhardt, D., Taylor, T., Dillon, C., Read, R., Cake, M., Little, C. (2009), Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 18(0), 479-89. [Abstract]
  • Xue, M., Smith, M., Little, C., Sambrook, P., March, L., Jackson, C. (2009), Activated Protein C Mediates a Healing Phenotype In Cultured Tenocytes. Journal of cellular and molecular medicine. 13(4), 749-57. [Abstract]
  • Jackson, M., Smith, M., Smith, S., Jackson, C., Xue, M., Little, C. (2009), Activation of cartilage matrix metalloproteinases by activated protein C. Arthritis and Rheumatism. 60(3), 780-791. [Abstract]

2008

   
  • Cake, M., Read, R., Edwards, S., Smith, M., Burkhardt, D., Little, C., Ghosh, P. (2008), Changes in gait after bilateral meniscectomy in sheep: effect of two hyaluronan preparations. Journal of Orthopaedic Science. 13(6), 514-523. [Abstract]
  • Fitzgerald, J., Rich, C., Burkhardt, D., Allen, J., Herzka, A., Little, C. (2008), Evidence for articular cartilage regeneration in MRL/MpJ mice. Osteoarthritis and Cartilage. 16(11), 1319-1326. [Abstract]
  • Wilson, R., Belluoccio, D., Little, C., Fosang, A., Bateman, J. (2008), Proteomic characterization of mouse cartilage degradation in vitro. Arthritis and Rheumatism. 58(10), 3120-3131. [Abstract]
  • Melrose, J., Smith, S., Little, C., Moore, R., Vernon-Roberts, B., Fraser, R. (2008), Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 17(9), 1131-48. [Abstract]
  • Fosang, A., Little, C. (2008), Drug insight: aggrecanases as therapeutic targets for osteoarthritis. Nature clinical practice. Rheumatology. 4(8), 420-427. [Abstract]
  • Smith, M., Cake, M., Ghosh, P., Schiavinato, A., Read, R., Little, C. (2008), Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy. Rheumatology (Oxford, England). 47(8), 1172-8. [Abstract]
  • Melrose, J., Hayes, A., Whitelock, J., Little, C. (2008), Perlecan, the "jack of all trades" proteoglycan of cartilaginous weight-bearing connective tissues. BioEssays : news and reviews in molecular, cellular and developmental biology. 30(5), 457-469. [Abstract]
  • Smith, M., Sakurai, G., Smith, S., Young, A., Melrose, J., Stewart, C., Appleyard, R., Peterson, J., Gillies, R., Dart, A., Sonnabend, D., Little, C. (2008), Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain. Arthritis and rheumatism. 58(4), 1055-1066. [Abstract]
  • Melrose, J., Smith, S., Smith, M., Little, C. (2008), The use of Histochoice for histological examination of articular and growth plate cartilages, intervertebral disc and meniscus. Biotechnic & Histochemistry. 83(1), 47-53. [Abstract]
  • Melrose, J., Smith, S., Appleyard, R., Little, C. (2008), Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 17(0), 314-24. [Abstract]
  • Gauci, S., Golub, S., Tutolo, L., Little, C., Sims, N., Lee, E., Mackie, E., Fosang, A. (2008), Modulating chondrocyte hypertrophy in growth plate and osteoarthritic cartilage. Journal of musculoskeletal & neuronal interactions. 8(4), 308-10. [Abstract]
  • Alini, M., Eisenstein, S., Ito, K., Little, C., Kettler, A., Masuda, K., Melrose, J., Ralphs, J., Stokes, I., Wilke, H. (2008), Are animal models useful for studying human disc disorders/degeneration?. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 17(0), 2-19. [Abstract]
  • Little, C., Smith, M. (2008), Animal models of osteoarthritis. Current Rheumatology Reviews. 4, 175-182.
  • Melrose, J., Fuller, E., Roughley, P., Smith, M., Kerr, B., Hughes, C., Caterson, B., Little, C. (2008), Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis research & therapy. 10(4), R79. [Abstract]