Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development.
Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development.
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DOI：
10.1186/ar4037
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发表时间：
2012-09-20
影响因子：
4.9
通讯作者：
Hamilton JA
中科院分区：
文献类型：
--
作者：
Cook AD;Pobjoy J;Steidl S;Dürr M;Braine EL;Turner AL;Lacey DC;Hamilton JA
粒细胞-巨噬细胞集落刺激因子（GM-CSF）已被证明在类风湿性关节炎炎症模型的发展中是重要的，并且有令人鼓舞的数据表明其阻断可能在类风湿性关节炎患者中具有临床意义。本研究的目的是确定GM-CSF是否对骨关节炎模型中的疾病和疼痛发展也很重要。使用胶原酶诱导的骨关节炎不稳定模型研究GM-CSF的作用。我们研究了GM-CSF-/-小鼠和野生型（C57 BL/6）小鼠用抗GM-CSF单克隆抗体进行免疫治疗或治疗。通过组织学评估疾病发展（早期和晚期），通过评估体重分布测量膝关节疼痛发展。在不存在GM-CSF的情况下，在疾病诱导后第2周存在较少的滑膜炎和基质金属蛋白酶介导的新表位表达，并且在第6周存在较少的软骨损伤。GM-CSF是疼痛发展所必需的。GM-CSF的治疗性中和不仅在3天内消除了疼痛，而且还导致软骨损伤显著减少。GM-CSF是实验性骨关节炎及其相关疼痛发展的关键。重要的是，通过治疗性单克隆抗体为基础的协议，GM-CSF中和迅速和完全消除现有的关节炎疼痛和抑制关节炎的发展程度。我们的研究结果表明，这将是值得探讨的重要性，GM-CSF的疼痛和疾病在其他骨关节炎模型，也许临床上这种形式的关节炎。
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. 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. 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. 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.
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影响因子：
27.4
作者：
Kortekaas, Marion C.;Kwok, Wing-Yee;Kloppenburg, Margreet
通讯作者：
Kloppenburg, Margreet
影响因子：
27.4
作者：
Burmester, Gerd R.;Feist, Eugen;Magrini, Fabio
通讯作者：
Magrini, Fabio
影响因子：
5.6
作者：
HAMILTON, JA;STANLEY, ER;SHADDUCK, RK
通讯作者：
SHADDUCK, RK
DOI：
10.1186/ar318
发表时间：
2001
期刊：
Arthritis research
影响因子：
--
作者：
Cook AD;Braine EL;Campbell IK;Rich MJ;Hamilton JA
通讯作者：
Hamilton JA
影响因子：
4
作者：
Iannone, F;Lapadula, G
通讯作者：
Lapadula, G