Abstract
IntroductionOsteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT).MethodsMale Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection.ResultsInterestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes.ConclusionsThese findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments.
Highlights
Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone
There was a significant increase in total bone volume (BV), bone volume fraction (BV/TV), Tb.Th, Tb.N, and Pl.Th. in the tibial subchondral bone of both the MIAinjected knee and the control knee over time (P < 0.05, Figure 3)
At two weeks there was a significant decrease in BV and BV/TV in the monosodium iodoacetate (MIA)-injected tibia compared to the control tibia, in both the medial and the total compartments (-18% and -14%, respectively, P < 0.05 for both parameters)
Summary
Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Osteoarthritis (OA) is generally a slow progressive joint disease characterized by loss of articular cartilage, subchondral bone sclerosis, cysts, and osteophyte formation [1]. Animal models of OA are of considerable importance as they are useful to study the pathogenesis and progression of OA, and to evaluate suitable therapeutic drugs for OA treatment. As early as after two weeks, high-dose MIA induced characteristic features of end-stage human OA such as loss of tibial articular cartilage, exposure of subchondral bone, subchondral trabecular bone erosion, cysts and osteophytes. These changes were observed only at ten weeks in the low-dose MIA model (Mohan G et al: unpublished observations). The low-dose MIA model, of relatively slow progressing OA, enables in vivo monitoring of tissue-level changes representative of progressive human OA; whereas, in the high-dose model the disease progression is very rapid, which is less suitable for longitudinal monitoring of cartilage and subchondral bone changes
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