Print Email Facebook Twitter Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought Title Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought Author Kozijn, A.E. Gierman, L.M. van der Ham, F. Mulder, P. Morrison, M.C. Kühnast, S. van der Heijden, R.A. Stavro, P.M. van Koppen, A. Pieterman, E.J. van den Hoek, A.M. Kleemann, R. Princen, H.M.G. Mastbergen, S.C. Lafeber, F.P.J.G. Zuurmond, A.M. Bobeldijk, I. Weinans, H. Stoop, R. Publication year 2018 Abstract Objective. Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. Design. Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr−/−. Leiden and ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. Results. Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr−/−. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. Conclusions. Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingOsteoarthritisMetabolic dysfunctionHigh-fat dietObesityMouse model To reference this document use: http://resolver.tudelft.nl/uuid:e0ad0e91-6df1-4804-aa5c-3a81378b8664 DOI https://doi.org/10.1016/j.joca.2017.10.010 TNO identifier 782690 Source Osteoarthritis and Cartilage, 25 (1), 95-107 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.