Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis
Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis
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DOI：
10.1016/j.joca.2012.04.014
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发表时间：
2012-07-01
影响因子：
7
通讯作者：
Haudenschild, D. R.
中科院分区：
文献类型：
--
作者：
Christiansen, B. A.;Anderson, M. J.;Haudenschild, D. R.
目的：创伤后骨关节炎（PTOA）是创伤性关节损伤的常见后果，50%的前交叉韧带（ACL）断裂患者在10-20年内发生PTOA。目前接受的PTOA小鼠模型使用各种方法引发症状，其中没有一种方法忠实地模拟临床相关的损伤状况。在这项研究中，我们描述了一种新的非侵入性小鼠PTOA模型，该模型在胫骨压缩过载的单一载荷下损伤ACL。我们利用这个模型来确定的时间过程中的关节软骨和软骨下骨的变化后knee injure.Design：小鼠被安乐死1，3，7，14，28，或56天后，非侵入性膝关节损伤。使用显微计算机断层扫描（mu CT）扫描膝关节，以量化软骨下骨小梁、软骨下骨板和非原生骨形成（异位骨化）。使用国际骨关节炎研究协会（OARS！）结果：受伤后，我们观察到一个快速的损失，在受伤的膝盖骨小梁相比，未受伤的膝盖受伤后7天，然后由一个部分恢复到一个新的稳定状态，由28天后受伤后。我们还观察到相当大的非原生骨形成损伤后56天。组织学切片的分级显示关节软骨损伤后56天恶化，符合轻度OA的发展。结论：本研究建立了一种新的小鼠模型PTOA，并描述了膝关节损伤后肌肉骨骼变化的时间过程，有助于建立预防性治疗的机会窗口。(C)2012年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Post-traumatic osteoarthritis (PTOA) is a common consequence of traumatic joint injury, with 50% of anterior cruciate ligament (ACL) rupture patients developing PTOA within 10-20 years. Currently accepted mouse models of PTOA initiate symptoms using various methods, none of which faithfully mimic clinically-relevant injury conditions. In this study we characterize a novel non-invasive mouse model of PTOA that injures the ACL with a single load of tibial compression overload. We utilize this model to determine the time course of articular cartilage and subchondral bone changes following knee injury.Design: Mice were euthanized 1, 3, 7, 14, 28, or 56 days after non-invasive knee injury. Knees were scanned using micro-computed tomography (mu CT) in order to quantify subchondral trabecular bone, subchondral bone plate, and non-native bone formation (heterotopic ossification). Development of osteoarthritis (OA) was graded using the osteoarthritis research society international (OARS!) scale on histological sections of injured and uninjured knees.Results: Following injury we observed a rapid loss of trabecular bone in injured knees compared to uninjured knees by 7 days post-injury, followed by a partial recovery of trabecular bone to a new steady state by 28 days post-injury. We also observed considerable non-native bone formation by 56 days post-injury. Grading of histological sections revealed deterioration of articular cartilage by 56 days post-injury, consistent with development of mild OA.Conclusions: This study establishes a novel mouse model of PTOA, and describes the time course of musculoskeletal changes following knee injury, helping to establish the window of opportunity for preventative treatment. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.