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

Autor: Haase T; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., Sunkara V; Computational Medicine, Dep. of Numerical Mathematics, Konrad Zuse Institute, Berlin, Germany.; Systems Pharmacology and Disease Control, Dep. of Mathematics & Computer Science, Freie Universität Berlin, Berlin, Germany., Kohl B; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., Meier C; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., Bußmann P; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., Becker J; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., Jagielski M; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany., von Kleist M; Systems Pharmacology and Disease Control, Dep. of Mathematics & Computer Science, Freie Universität Berlin, Berlin, Germany., Ertel W; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Traumatology and Reconstructive Surgery, Berlin, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Apr 11; Vol. 14 (4), pp. e0213734. Date of Electronic Publication: 2019 Apr 11 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0213734
Abstrakt: 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.
Competing Interests: All authors declare that they have no competing financial interests.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje