Objective
To assess temporal changes in cartilage and bone morphology, reactive oxygen species (ROS), and vascularization in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats via advanced imaging methodologies.
Methods
Right knees of male 8-week old Wistar rats were injected with 1mg MIA in 50µl saline and left knee controls injected with 50µl saline. After 1, 2, and 3 weeks (n=5 each), changes in cartilage morphology and composition were quantified using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) and changes in subchondral and trabecular bone were assessed by standard µCT. ROS were characterized via in vivo fluorescence imaging at 1, 11, and 21 days (n=5 each). At 3 weeks, after fluorescence imaging, alterations in knee joint vascularity were quantified with µCT after vascular contrast agent perfusion (n=5).
Result
Femoral cartilage volume, thickness, and proteoglycan content were significantly decreased in MIA injected knees compared to controls, accompanied by loss of trabecular bone and erosion of subchondral bone surface. ROS quantities were significantly increased 1 day after MIA injection and were gradually relieved by 21 days. Vascularity in the whole knee and distal femora was significantly increased at 3 weeks after MIA injection.
Conclusion
Contrast-enhanced µCT and fluorescence imaging were combined to characterize articular cartilage, subchondral bone, vascularization, and ROS, providing unprecedented 3-D joint imaging and quantification for multiple tissues during OA progression. These advanced imaging techniques have the potential to become standardized methods for comprehensive evaluation of articular joint degeneration and characterization of therapeutics.