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

The accurate and sensitive detection of radical oxidants is a central problem in the field of chemical biology.[1] Radical oxidants can be detected in vitro with fluorescent leucodyes such as dihydroethidium (DHE),[2] dihydrorhodamine (DHR),[3] the hydrocyanines,[4] redoxfluor-1,[5a] and their organelle-specific analogues.[5b] Although these probes are widely used in cell culture, their accuracy is compromised by their high levels of background fluorescence,[6] which is caused by their spontaneous oxidation that is catalyzed by light or oxygen. Radical oxidants can be detected by using DHE, DHR, and the hydrocyanines, as they undergo an amine oxidation reaction[7] with cellular oxidants, such as superoxide or hydroxyl radicals. However, the probes also generate background fluorescence by undergoing the same amine oxidation reaction with air and light; this reaction is often attributed to the effects of singlet oxygen (1O2).[8]

Asymmetric catalysis of Mukaiyama aldol addition reactions of methyl 3-TMSO-2-diazo-3-butenoate 4 with aromatic aldehydes using AgF/( R )-BINAP at −20 °C produces chiral diazoacetoacetates in high chemical yields and with high enantiocontrol.