@article{HaaseSunkaraKohletal., author = {Haase, Tobias and Sunkara, Vikram and Kohl, Benjamin and Meier, Carola and Bußmann, Patricia and Becker, Jessica and Jagielski, Michal and von Kleist, Max and Ertel, Wolfgang}, title = {Discerning the spatio-temporal disease patterns of surgically induced OA mouse models}, series = {PLOS One}, volume = {14}, journal = {PLOS One}, number = {4}, publisher = {PLOS One}, doi = {10.1371/journal.pone.0213734}, 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.}, language = {en} }