Dataset Information

Discerning the spatio-temporal disease patterns of surgically induced OA mouse models.

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.

SUBMITTER: Haase T

PROVIDER: S-EPMC6459499 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Discerning the spatio-temporal disease patterns of surgically induced OA mouse models.

Haase Tobias T Sunkara Vikram V Kohl Benjamin B Meier Carola C Bußmann Patricia P Becker Jessica J Jagielski Michal M von Kleist Max M Ertel Wolfgang W

PloS one 20190411 4

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 chond ...[more]

PMID: 30973882

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Project description:BackgroundTransmission mechanisms of black-band disease (BBD) in coral reefs are poorly understood, although this disease is considered to be one of the most widespread and destructive coral infectious diseases. The major objective of this study was to assess transmission mechanisms of BBD in the field based on the spatio-temporal patterns of the disease.Methodology/principal findings3,175 susceptible and infected corals were mapped over an area of 10x10 m in Eilat (northern Gulf of Aqaba, Red Sea) and the distribution of the disease was examined monthly throughout almost two full disease cycles (June 2006-December 2007). Spatial and spatio-temporal analyses were applied to infer the transmission pattern of the disease and to calculate key epidemiological parameters such as (basic reproduction number). We show that the prevalence of the disease is strongly associated with high water temperature. When water temperatures rise and disease prevalence increases, infected corals exhibit aggregated distributions on small spatial scales of up to 1.9 m. Additionally, newly-infected corals clearly appear in proximity to existing infected corals and in a few cases in direct contact with them. We also present and test a model of water-borne infection, indicating that the likelihood of a susceptible coral becoming infected is defined by its spatial location and by the relative spatial distribution of nearby infected corals found in the site.Conclusions/significanceOur results provide evidence that local transmission, but not necessarily by direct contact, is likely to be an important factor in the spread of the disease over the tested spatial scale. In the absence of potential disease vectors with limited mobility (e.g., snails, fireworms) in the studied site, water-borne infection is likely to be a significant transmission mechanism of BBD. Our suggested model of water-borne transmission supports this hypothesis. The spatio-temporal analysis also points out that infected corals surviving a disease season appear to play a major role in the re-introduction of the disease to the coral community in the following season.

Dataset Information

Discerning the spatio-temporal disease patterns of surgically induced OA mouse models.

Publications

Discerning the spatio-temporal disease patterns of surgically induced OA mouse models.

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