Systematic analysis reveals that colony housing aligns gait profiles and strengthens link between histological and micro-CT bone markers in rat models of osteoarthritis

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.