Maninchedda Ugo, Lepage Olivier M, Gangl Monika, Hilairet Sandrine, Remandet Bernard, Meot Francoise, Penarier Geraldine, Segard Emilie, Cortez Pierre, Jorgensen Christian, Steinberg Régis
Equine Research Centre, University of Lyon, VetAgro Sup, Veterinary Campus of Lyon, GREMERES-ICE, Marcy l'Etoile, France.
Exploratory Unit, Sanofi-aventis Recherche, Montpellier, France.
PLoS One. 2015 Feb 13;10(2):e0115089. doi: 10.1371/journal.pone.0115089. eCollection 2015.
The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.
这项工作的目的是开发一种诱导骨关节炎的马掌指关节模型,该模型并非主要由不稳定或炎症介导。该研究涉及六匹标准赛马。通过关节镜在随机选择的一侧肢体的外侧和内侧掌骨髁远端背侧创建标准化的软骨表面损伤或“凹槽”。对侧肢体进行假手术。在厩内休息2周后,马匹每隔一天小跑30分钟,持续8周,然后评估跛行情况并进行X光检查。分析滑液的细胞学和生物标志物。术后10周,对马匹实施安乐死以进行关节的宏观和组织学评估。关节镜下开槽可对所有动物的软骨造成精确且相同的损伤。在受控的运动方案下,这种骨关节炎凹槽模型显示出显著的X光、宏观和微观退行性及反应性变化。组织学显示手术诱导的凹槽一致,仅限于未钙化的软骨,并伴有继发性相邻软骨病变、软骨细胞坏死、软骨细胞簇、软骨基质软化、裂隙、轻度软骨下骨炎症、水肿和成骨细胞边缘。滑液生物化学和细胞学显示总蛋白显著升高,而前列腺素E2、中性粒细胞或软骨细胞未增加。这种马掌指关节凹槽模型表明,标准化的未钙化软骨损伤伴运动引发了骨软骨形态改变和软骨退变,修复极少或无效,炎症反应轻微。该模型若经验证,将可用于评估疾病进程及治疗效果。