Characterisation of growth plate dynamics in murine models of osteoarthritis

Abstract

Objective: To investigate growth plate (GP) dynamics in surgical and loading murine models of osteoarthritis (OA), to understand whether abnormalities in these dynamics predict those at risk of OA. Methods: 8-week-old C57BL/6 male mice underwent destabilization of medial meniscus (DMM) (n=8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n=4), OA was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage (AC) and GP was examined by histology and immunohistochemistry. Tibial subchondral bone (SCB) parameters were measured using microCT and correlated to GP bridging. Results: Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial AC chondrocytes of DMM and loaded mice. In tibial GP, Col10a1 and MMP13 expressions were widely dispersed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes (P>0.001). 3-dimensional quantification revealed enriched GP bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. GP dynamics were associated with increased SCB and epiphyseal trabecular bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints respectively. Conclusions: Results confirm associations between aberrant chondrocyte hypertrophy marker expression and OA pathology in a surgical and loaded murine model of OA. Spatial variations in GP bridging formation revealed accelerated cartilage-bone transitions which may contribute to anatomical variation in vulnerability to OA development in these models.