Abstract
Osteoarthritis (OA) is the most common cause of disability in ageing societies, with no effective therapies available to date. Two preclinical models are widely used to validate novel OA interventions (MCL-MM and DMM). Our aim is to discern disease dynamics in these models to provide a clear timeline in which various pathological changes occur. OA was surgically induced in mice by destabilisation of the medial meniscus. Analysis of OA progression revealed that the intensity and duration of chondrocyte loss and cartilage lesion formation were significantly different in MCL-MM vs DMM. Firstly, apoptosis was seen prior to week two and was narrowly restricted to the weight bearing area. Four weeks post injury the magnitude of apoptosis led to a 40–60% reduction of chondrocytes in the non-calcified zone. Secondly, the progression of cell loss preceded the structural changes of the cartilage spatio-temporally. Lastly, while proteoglycan loss was similar in both models, collagen type II degradation only occurred more prominently in MCL-MM. Dynamics of chondrocyte loss and lesion formation in preclinical models has important implications for validating new therapeutic strategies. Our work could be helpful in assessing the feasibility and expected response of the DMM- and the MCL-MM models to chondrocyte mediated therapies.
Highlights
Osteoarthritis (OA) is one of the most common degenerative diseases of the musculoskeletal system affecting millions of people with a major loss in life quality
We focus on two meniscectomy based methods: the Medial Collateral Ligament-Medial Meniscus transection model (MCL-MM) and the Destabilisation Medial Meniscus model (DMM)
Since the MCL-MM sham procedure is likely to be more severe than the DMM sham procedure; we used it as a conservative candidate for baseline measurements
Summary
Osteoarthritis (OA) is one of the most common degenerative diseases of the musculoskeletal system affecting millions of people with a major loss in life quality. Due to the lack of regenerative capacity of the articular cartilage, OA is a progressive disease leading to increasing functional impairment of the joints. Spatio-temporal disease patterns of OA mouse models. OA development in weight bearing joints has been associated with ageing, obesity, incorrect loading, and joint trauma. A state of chronic systemic inflammation that accompanies the metabolic syndrome is thought to contribute to OA development and progression [5]. In view of a rapidly ageing population combined with the epidemic of obesity and sedentary lifestyle, the prevalence of OA in the future is expected to rise [6]
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