School of Veterinary and Biomedical Sciences, Murdoch University, Perth, WA 6150, Australia.
Osteoarthritis Cartilage. 2013 Jan;21(1):226-36. doi: 10.1016/j.joca.2012.10.001. Epub 2012 Oct 13.
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.
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.
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.
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.
羊的半月板切除术（MX）可诱导出一种成熟的人类骨关节炎（OA）动物模型。本研究比较了单侧、完全内侧半月板 MX 与两种创伤较小且更容易实施的半月板不稳定处理方法的临床（跛行）和病理结果。
4 岁的绵羊（每组 n = 6）接受了假手术、颅极点释放（CPR）、中体横断（MBT）或内侧半月板全切除术。术后 12 周，通过大体病理（软骨侵蚀和骨赘）、组织形态计量学、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 切割的新表位的免疫组化，对关节进行评估。在亚组（每组 n = 4）中，通过测力板在基线、术后 2.5、8 和 12 周时确定地面反力（GRF）。
手术组的大体病理评分与假手术动物有显著差异（P < 0.05），但彼此之间没有差异，尽管存在定性差异：CPR 绵羊出现更多的颅侧和局灶性病变，而 MBT 和 MX 关节表现出更广泛的病变和骨赘形成。同样，组织病理学评分与假手术相比显著升高，但在术后 12 周时，各组之间没有差异（P < 0.05），除了 MBT 模型中胫骨软骨组织病理学评分较低的趋势，这与该模型中聚集酶裂解新表位减少的免疫组化模式一致。CPR 绵羊的股骨软骨下硬化程度较低，这表明不稳定但完整的半月板仍有一定的生物力学作用。在测力板分析中，各组之间很少有显著差异，尽管 CP 绵羊的步态异常似乎最少，而 MBT 动物的异常持续时间最长（>12 周）。
经过充分验证的绵羊 MX 模型和更简单的半月板不稳定处理方法导致了广泛相似的关节病理和跛行。半月板 CPR 或 MBT 作为更简单且更具临床相关性的方法，可能代表了诱导 OA 和评估潜在疾病修饰治疗的首选模型。
