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




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Arthritis Research and Therapy

, 14:R199

First Online: 20 September 2012Received: 27 April 2012Revised: 02 August 2012Accepted: 20 September 2012

Abstract

IntroductionGranulocyte-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.

MethodsThe 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.

ResultsIn 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.

ConclusionsGM-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.

AbbreviationsGM-CSFgranulocyte-macrophage colony-stimulating factor

H and Ehematoxylin and eosin

ILinterleukin

mAbmonoclonal antibody

MMPmatrix metalloproteinase

OAosteoarthritis

PBSphosphate-buffered saline

RArheumatoid arthritis

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4037 contains supplementary material, which is available to authorized users.

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