The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse
The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse
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DOI：
10.1016/j.joca.2007.03.006
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发表时间：
2007-09-01
影响因子：
7
通讯作者：
Morris, E. A.
中科院分区：
文献类型：
--
作者：
Glasson, S. S.;Blanchet, T. J.;Morris, E. A.
目的：评估129/SvEv小鼠膝关节骨关节炎（OA）的前交叉韧带横断（ACLT）和内侧半月板失稳（DMM）手术不稳定模型。
设计：在直视下使用显微外科技术进行ACLT或DMM操作。对多个切片进行组织学评分以评估整个关节的软骨损伤情况。
结果：ACLT模型导致严重的OA、关节囊软骨形成，在某些情况下，胫骨平台后部出现严重的软骨下骨侵蚀。手术性DMM比ACLT手术的侵入性小，主要导致胫骨内侧平台和股骨内侧髁的中央负重区域出现病变。DMM模型中的病变在术后4周从轻度至中度软骨退变进展，到术后8周从中度至重度软骨退变。在DMM模型中从未观察到软骨下骨破坏。
结论：由于ACLT对手术熟练程度要求高且可能导致涉及软骨下骨侵蚀的严重OA，因此不建议在小鼠中使用。DMM后的病变严重程度和位置与在老年自发性小鼠OA模型中观察到的病变一致。如在含ADAMTS - 5基因敲除（KO）小鼠中所观察到的，DMM模型对显示疾病改善具有足够的敏感性。DMM模型应该是对具有骨关节炎潜在靶点基因缺失的小鼠进行研究的首选。（C）2007国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To evaluate anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgical instability models of osteoarthritis (OA) in the 129/SvEv mouse knee joint.Design: Micro-surgical techniques were used to perform ACLT or DMM under direct visualization. Histological scoring was performed on multiple sections to assess cartilage damage across the entire joint.Results: The ACLT model gave severe OA, chondrogenesis of the joint capsule and, in some cases, severe subchondral erosion of the posterior tibial plateau. Surgical DMM was less invasive than the ACLT procedure and resulted in lesions primarily on the central weight-bearing region of the medial tibial plateau and medial femoral condyles. Lesions in the DMM model progressed from mild-to-mode rate CA at 4 weeks, to mode rate-to-severe CA at 8 weeks post-surgery. Destruction of the subchondral bone was never observed in the DMM model.Conclusions: ACLT is not recommended in the mouse due to the high surgical proficiency required and the development of severe OA that may involve subchondral bone erosion. The severity and location of lesions following DMM are consistent with lesions observed in aged spontaneous mouse models of OA. The DMM model has sufficient sensitivity to show disease modification, as observed with the ADAMTS-5 knock out (KO) mouse. The DMM model should be a first choice to challenge mice with gene deletions of potential targets in OA. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.