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Open Access Research article

Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development

Andrew D Cook1*, Jarrad Pobjoy1, Stefan Steidl2, Manuela Dürr2, Emma L Braine1, Amanda L Turner1, Derek C Lacey1 and John A Hamilton1

Author Affiliations

1 Arthritis and Inflammation Research Centre, Department of Medicine, The University of Melbourne, Victoria, 3010, Australia

2 MorphoSys AG, Lena-Christ-Strasse 48, Martinsried/Planegg, 82152, Germany

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Arthritis Research & Therapy 2012, 14:R199  doi:10.1186/ar4037

Published: 20 September 2012

Abstract

Introduction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be important in the development of inflammatory models of rheumatoid arthritis and there is encouraging data that its blockade may have clinical relevance in patients with rheumatoid arthritis. The aims of the current study were to determine whether GM-CSF may also be important for disease and pain development in a model of osteoarthritis.

Methods

The role of GM-CSF was investigated using the collagenase-induced instability model of osteoarthritis. We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease development (both early and late) was evaluated by histology and knee pain development was measured by assessment of weight distribution.

Results

In the absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated neoepitope expression at week 2 post disease induction, and less cartilage damage at week 6. GM-CSF was absolutely required for pain development. Therapeutic neutralization of GM-CSF not only abolished the pain within 3 days but also led to significantly reduced cartilage damage.

Conclusions

GM-CSF is key to the development of experimental osteoarthritis and its associated pain. Importantly, GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly and completely abolished existing arthritic pain and suppressed the degree of arthritis development. Our results suggest that it would be worth exploring the importance of GM-CSF for pain and disease in other osteoarthritis models and perhaps clinically for this form of arthritis.