Article thumbnail

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

By A.E. Kozijn, L.M. Gierman, F. van der Ham, P. Mulder, M.C. Morrison, S. Kühnast, R.A. van der Heijden, P.M. Stavro, A. van Koppen, E.J. Pieterman, A.M. van den Hoek, R. Kleemann, H.M.G. Princen, S.C. Mastbergen, F.P.J.G. Lafeber, A.M. Zuurmond, I. Bobeldijk, H. Weinans and R. Stoop

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

Year: 2018
DOI identifier: 10.1016/j.joca.2017.10.010
OAI identifier:
Provided by: NARCIS
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.loc.gov/mods/v3 (external link)
  • http://oai.tudelft.nl/tno (external link)
  • http://resolver.tudelft.nl/uui... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.