Subchondral bone remodelling and osteophyte growth are widely recognised hallmarks of knee osteoarthritis (OA) although their contribution to disease is not fully understood. Murine models, with targeted genetic modifications, have become powerful tools for discovering disease pathophysiology. Our unpublished observations suggest that osteophyte formation is independent of cartilage loss thereby implying potentially independent molecular drivers. We have developed a novel imaging method to automatically quantify osteophyte growth and subchondral bone remodelling in murine OA.
OA was induced by surgical destabilization of the medial meniscus (DMM) in the right knee joint. 10-week-old C57Bl/6J mice (n=6) were operated and sacrificed at 1, 2, 4, 8, 12, and 20 weeks post-surgery. The tibia was imaged by microCT (5 μm/pixel) and analysed by our automated software (Matlab code). Whole epiphyseal volumes were computed from virtually dissected epiphyses (above the growth plate) and any internal porosity was included in the total volume calculation.
Automated analysis revealed significant tibial plate thickening from 2 weeks post-surgery, epiphyseal trabecular volume fraction increased and whole epiphyseal volume was expanded from 4 weeks in the DMM group compared with the contralateral. Medial osteophytes were identified by microCT, starting at 4 weeks post-DMM surgery, and confirmed by histology. Osteophyte volume at 4 weeks was 3±0.3% of the whole epiphysis volume in the DMM group, and up to 4% at 20 weeks post-surgery. However, osteophyte growth showed strong correlation with whole epiphysis expansion only at 20 weeks post-DMM, implying that additional shape modelling contributed to the expansion in earlier time points.
Our quantitative automated image analysis identified bone changes, including subchondral plate and trabecular sclerosis and osteophyte growth, from early stages in the DMM model of murine OA. This represents a robust and potentially high throughput method for the assessment of bone structural changes in murine OA.
18 - 21 May 2013
European Calcified Tissue Society