Comparison of gait and pathology outcomes of three meniscal procedures for induction of knee osteoarthritis in sheep
Comparison of gait and pathology outcomes of three meniscal procedures for induction of knee osteoarthritis in sheep
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DOI：
10.1016/j.joca.2012.10.001
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Little, C. B.
中科院分区：
文献类型：
--
作者：
Cake, M. A.;Read, R. A.;Little, C. B.
目的：羊半月板切除术（MX）诱导建立人骨关节炎（OA）动物模型。本研究比较了单侧完整内侧MX与两种创伤较小且更容易实施的半月板不稳定手术的临床（跛行）和病理结果。方法：采用假手术、颅极松解术（CPR）、中体横断术（MBT）或内侧半月板全切除术（MX）对4岁大的新生儿（6例/组）进行治疗。术后12周，对关节进行大体病理（软骨糜烂和骨癣）、组织形态学、两种组织病理学评分方法（改良的mankin型和Pritzker评分）以及ADAMTS和mmp切割新表位的免疫组织学评估。在基线、术后2.5周、8周和12周，通过力板测定各组（n = 4/组）的地面反作用力（GRFs）。结果：手术组大体病理评分与假手术组比较差异有统计学意义（P < 0.05），但两组间差异无统计学意义（P < 0.05），但存在定性差异：CPR羊出现更多的颅脑和局灶性病变，而MBT和MX关节出现更广泛的病变和骨赘形成。同样，与假手术相比，组织病理学评分显著升高，但在手术组之间没有差异（P < 0.05），除了MBT中下胫软骨组织病理学的趋势与该模型中聚集酶酶切割新表位减少的免疫组织学模式一致。心肺复苏术绵羊较少出现股骨软骨下硬化症，提示失稳但完整的半月板存在一些残留的生物力学效应。在力板分析中，手术组之间没有明显差异，尽管步态异常在心肺复苏术羊中最少，在MBT动物中最持久（bb0 - 12周）。结论：经过验证的羊MX模型和更简单的半月板不稳定手术导致了广泛相似的关节病理和跛行。半月板心肺复苏术或MBT作为更容易和更具有临床相关性的手术，可能是诱导OA和评估潜在疾病改善疗法的首选模型。(C) 2012国际骨关节炎学会。Elsevier Ltd.出版。版权所有。
Objective(s): Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures.Methods: Four-year old wethers (n = 6/group) underwent sham operation, cranial pole release (CPR), mid-body transection (MBT) or total MX of the medial meniscus. Joints were assessed for gross pathology (cartilage erosion and osteophytes), histomorphometry, two histopathology scoring methods (modified Mankin-type and Pritzker score), and immunohistology for ADAMTS- and MMP-cleaved neoepitopes, at 12 weeks post-op. Ground reaction forces (GRFs) were determined by force plate in a subset (n = 4/group) at baseline, 2.5, 8, and 12 weeks post-op.Results: Gross pathology scores of operated groups differed significantly from sham animals (P < 0.05) but not from each other, though qualitative differences were noted: CPR sheep developed more cranial and focal lesions, while MBT and MX joints showed more widespread lesions and osteophyte formation. Similarly, histopathology scores were significantly elevated vs sham but did not differ between operated groups at P < 0.05, except for a trend for lower tibial cartilage histopathology in MBT consistent with the immunohistologic pattern of reduced aggrecanase-cleavage neoepitope in that model. CPR sheep developed less femoral subchondral sclerosis, suggesting some residual biomechanical effect from the destabilised but intact meniscus. Few significant differences were noted between operated groups in force plate analyses, though gait abnormalities appeared to be least in CPR sheep, and most persistent (>12 weeks) in MBT animals.Conclusion: The well-validated ovine MX model and the simpler meniscal destabilisation procedures resulted in broadly similar joint pathology and lameness. Meniscal CPR or MBT, as easier and more clinically relevant procedures, may represent preferred models for the induction of OA and evaluation of potential disease-modifying therapies. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.