Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
Merck Healthcare KGaA, Darmstadt, Germany.
FASEB J. 2021 Apr;35(4):e21451. doi: 10.1096/fj.202002009R.
Osteoarthritis (OA) etiopathogenesis is complex with strong environmental/lifestyle determinants that, in laboratory animals, extend to social context and stress levels. This study seeks to identify whether colony housing of rats exerts a social impact on locomotion behaviors to influence alignment between symptomatic (gait) and structural (bone micro-CT measures, cartilage morphometry, and histology) OA outcome measures. Rats were randomly allocated to conventional (type IV; n = 48) or rat colony cage (RCC; n = 30) housing, further randomized to OA surgical models (ACLT + tMx, MMT or DMM) or no surgery (control), and maintained for 19 weeks during which multiple gait recordings were made. Standard histological grading and bone micro-CT data were collected at necropsy. Principal component analysis was used to summarize the variation in gait, micro-CT or histology. Linear mixed effects model or two-way ANOVA was employed to evaluate the impact of the housing system, surgery and time on gait, or micro-CT and histology components Analyses reveal that RCC exaggerates trends in gait change via a combined effect of the housing system and surgery. Intriguingly, RCC-housed nonoperated control rats showed similar gait changes to rats subjected to surgery; the latter exhibited significant structural joint changes in both systems. Stronger correlation between histological and micro-CT bone changes were found in medial and lateral tibia joint compartments of rats housed in RCC system. This study has established that rat social housing exaggerates outcomes in traditional histological measures of OA, generates stronger links between histology and micro-CT bone changes and removes gait differences as a variable in their etiology.
骨关节炎 (OA) 的发病机制复杂，受强烈的环境/生活方式决定因素影响，在实验室动物中，这些因素还扩展到社会环境和压力水平。本研究旨在确定大鼠的群体饲养是否对运动行为产生社会影响，从而影响症状（步态）和结构（骨微 CT 测量、软骨形态计量学和组织学）OA 结果测量之间的一致性。大鼠被随机分配到传统（IV 型；n=48）或大鼠群体笼（RCC；n=30）饲养中，进一步随机分为 OA 手术模型（ACLT+tMx、MMT 或 DMM）或无手术（对照），并在 19 周内维持饲养，在此期间进行了多次步态记录。在尸检时收集了标准组织学分级和骨微 CT 数据。主成分分析用于总结步态、微 CT 或组织学的变化。线性混合效应模型或双向 ANOVA 用于评估饲养系统、手术和时间对步态或微 CT 和组织学成分的影响。分析表明，RCC 通过饲养系统和手术的综合作用夸大了步态变化的趋势。有趣的是，RCC 饲养的未手术对照大鼠表现出与手术大鼠相似的步态变化；后者在这两个系统中都表现出关节结构的显著变化。在 RCC 系统中饲养的大鼠的内侧和外侧胫骨关节腔中，发现组织学和微 CT 骨变化之间的相关性更强。本研究确立了大鼠社会饲养会夸大传统 OA 组织学测量的结果，在组织学和微 CT 骨变化之间产生更强的联系，并消除了步态差异作为其病因的一个变量。
