ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization
ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization
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DOI：
10.1016/j.joca.2009.11.013
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发表时间：
2010-04-01
影响因子：
7
通讯作者：
Mogil, J. S.
中科院分区：
文献类型：
--
作者：
Malfait, A. M.;Ritchie, J.;Mogil, J. S.
目的：研究野生型（WT）和ADAMTS-5缺失小鼠中由内侧半月板失稳（DMM）引起的膝关节骨性关节炎（OA）过程中疼痛相关行为的特征。方法：对CD-1小鼠右膝行DMM手术。在术后8周的定期间隔内，对小鼠进行以下参数评估：机械异常性痛（通过后爪或尾部施加von Frey纤维的戒断阈值），热痛感过敏，运动活动和步态分析。此外，在DMM手术后的C57BL/6 WT或ADAMTS-5小鼠中测试机械异常性疼痛。结果：在CD-1小鼠中，DMM后双后爪的戒断阈值明显下降，但假手术后无明显下降。异常性疼痛早在术后14天就出现了。术后并发机械异常性痛，男女均出现OA改变。术后8周未发现其他与疼痛相关的行为改变。在C57BL/6小鼠中，遗传背景是只有雄性在DMM后发生OA变化，雄性而雌性没有在同侧后爪发生异位性疼痛。相比之下，C57BL/6 ADAMTS-5缺失小鼠在术后8周内未发生OA变化或机械异常性疼痛。结论：小鼠DMM手术后关节病理与进行性机械异常性痛相关。ADAMTS-5缺失小鼠对dmm诱导的oa样病变和相关的机械异常性疼痛具有抗性。(C) 2010年由Elsevier Ltd代表国际骨关节炎研究学会出版。
Objective: To characterize pain-related behavior during the course of knee osteoarthritis (OA) induced by destabilization of the medial meniscus (DMM) in wild type (WT) and in ADAMTS-5 null mice.Methods: DMM surgery was performed in the right knee of CD-1 mice. At regular intervals up to 8 weeks after surgery, mice were assessed for the following parameters: mechanical allodynia (via withdrawal thresholds to von Frey filaments applied to the plantar surface of both hind paws or to the tail), thermal hyperalgesia, locomotor activity and gait analysis. In addition, mechanical allodynia was tested in C57BL/6 WT or ADAMTS-5 null mice following DMM surgery.Results: In CD-1 mice, a robust and progressive decrease in withdrawal threshold was observed in both hind paws after DMM but not sham surgery. Allodynia was apparent as early as 14 days postoperatively. Both sexes developed OA changes after surgery with concurrent mechanical allodynia. No other pain-related behavioral changes were detected up to 8 weeks post-surgery. In C57BL/6 mice, a genetic background in which only males develop OA changes after DMM, males but not females developed allodynia in the ipsilateral hind paw. In contrast, C57BL/6 ADAMTS-5 null mice did not develop OA changes or mechanical allodynia up to 8 weeks post-surgery.Conclusion: Joint pathology following DMM surgery in mice is associated with progressive mechanical allodynia. ADAMTS-5 null mice are resistant to DMM-induced OA-like lesions and to the associated mechanical allodynia. (C) 2010 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.