Characterizing a Novel and Adjustable Noninvasive Murine Joint Loading Model
Characterizing a Novel and Adjustable Noninvasive Murine Joint Loading Model
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DOI：
10.1002/art.27765
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Pitsillides, Andrew A.
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文献类型：
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作者：
Poulet, Blandine;Hamilton, Richard W.;Pitsillides, Andrew A.
客观的。通过机械适应性反应产生的机械负荷会改变关节软骨结构并导致骨关节炎 (OA)。然而，与关节健康和疾病有关的具体机械刺激仍然不清楚，部分原因是缺乏受控负荷的体内模型。本研究的目的是开发和表征一种新型非手术小鼠模型，其中施加到膝关节的负载是高度可调的。方法。除装载期间外，动物均经历正常运动。对 8 周龄 CBA 小鼠的右膝施加负荷，每周 3 次，持续 2 周（立即或无负荷 3 周后评估），或持续 5 周，或仅一次（立即或无负荷 2 周后评估）。检查了负载和对照对侧关节的组织学特征，包括关节软骨病变、骨赘形成和病理特征。通过微焦计算机断层扫描 (micro-CT) 进行加载过程中的离体可视化。结果。显微 CT 显示，两周的负载仅在最大接触部位产生关节软骨损伤； 3周后没有进一步负载，另一组相同负载的小鼠的关节显示平均病变严重程度显着增加至负载5周后的水平。单次施加负荷也会引起病变，但在本例中，仅习惯使用两周并不会导致进一步恶化。只有重复加载才会导致番红 O 染色丢失。负荷还导致骨赘形成、半月板骨化、滑膜增生和纤维化以及十字韧带病理，其严重程度取决于所采用的负荷方案。结论。我们首次描述了小鼠膝关节负荷的非侵入性模型。这将进一步研究关节健康以及骨关节炎发生和进展中的机械和遗传相互作用。
Objective. Mechanical loading through a mechano-adaptive response modifies articular cartilage structure and contributes to osteoarthritis (OA). However, the specific mechanical stimuli involved in joint health and disease remain poorly defined, partly due to a lack of in vivo models of controlled loading. The present study was undertaken to develop and characterize a novel nonsurgical murine model in which applied loads to the knee joint are highly adjustable.Methods. Animals experienced normal locomotion, except during loading. Loads were applied to the right knees of 8-week-old CBA mice, 3 times a week for 2 weeks (and assessed immediately or after 3 weeks of nonloading), or for 5 weeks, or just once (and assessed immediately or after 2 weeks of nonloading). Histologic features of loaded and control contralateral joints, including articular cartilage lesions, osteophyte formation, and pathologic features, were examined. Ex vivo visualization during loading was performed by microfocal computed tomography (micro-CT).Results. Two weeks of loading produced articular cartilage lesions only at sites of maximal contact as exhibited by micro-CT; after 3 weeks without further loading, joints in another group of mice identically loaded revealed significant increases in mean lesion severity to levels seen following 5 weeks of loading. Single application of load also induced lesions, but in this case, 2 weeks of solely habitual use did not lead to further deterioration. Only repetitive loading induced loss of Safranin O staining. Loading also led to osteophyte formation, meniscal ossification, synovial hyperplasia and fibrosis, and cruciate ligament pathology, with a severity that was dependent upon the loading regimen utilized.Conclusion. We describe for the first time a non-invasive model of murine knee joint loading. This will further the study of mechanical and genetic interactions in joint health and in OA initiation and progression.