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.
Highlights
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
Given that the major functions of Granulocyte-macrophage colony-stimulating factor (GMCSF) appear to be as a pro-survival and ‘activating’ factor for myeloid cells [2], in the current study we investigated whether this experimental OA model is dependent on GM-CSF
To determine whether an OA-like model was dependent on GMCSF, histology was performed on the joints of C57BL/6 and GM-CSF-/- mice at 6 weeks post collagenase intra-articular injection and disease scored according to the published protocol [31]
Summary
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 be important for disease and pain development in a model of osteoarthritis. Granulocyte-macrophage colony-stimulating factor (GMCSF) was originally defined as a hemopoietic growth factor [1]. It can act on mature myeloid cells [2] and it has other functions, acting as a proinflammatory cytokine [2,3,4,5] and in dendritic cell function [6].
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