Abstract

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.

Highlights

  • Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only

  • This study aims to understand how different tissue compartments in the knees of wild-type C57BL/6 mice from different age groups respond to DMM surgery by using cartilage histology scoring and quantitative micro-computed tomography analyses of subchondral bone plate thickness and osteophyte formation

  • Using C57BL/6 mice from 3 age groups, we determined that articular cartilage and subchondral bone respond to DMM differently with age

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Summary

Introduction

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/ gender when using this surgical technique for translational OA research. Age is the primary risk factor for developing osteoarthritis (OA), a chronic, degenerative joint disease that is characterized by progressive loss of articular cartilage and subchondral bone changes. Surgical destabilization of the medial meniscus (DMM) results in gradual deterioration of articular cartilage and subchondral bone changes, and is thought to recapitulate the progression of human OA pathology[10,11]. Young (~4 M) female mice were found to be less prone to developing OA following DMM compared to their male counterparts[21], but whether the perceived protective effect of sex hormone persists over age is unclear

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