OP0108 Diet induced metabolic changes in an osteoarthritis mouse model. (12th June 2018)

• Record Type: Journal Article
• Authors: Hülser, M.-L.; Schreiyaeck, C.; Luo, Y.; Bozec, A.; Schett, G.; Müller-Ladner, U.; Neumann, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 104
• Page End: 104
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.3082
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Adipose tissue is not only an energy depot, but also secrets bioactive factors such as adipokines. Several of these factors are known to regulate immune responses. Osteoarthritis (OA) is one of the most common joint diseases with obesity being a well known risk factor. Therefore, an obesity model (High-fat diet, HFD) was combined with an established model for OA (DMM, destabilisation of the medial meniscus) to evaluate the role of adipokines in this setting. Objectives: This work evaluates the influence of different adipokines on OA progression and obesity comparing systemic vs local effects at different time points. Methods: The study was performed in C57Bl/6 mice fed with HFD or ND (normal diet) prior to OA induction. Mice were sacrificed and analysed 4, 6 and 8 weeks after surgery. For systemic analysis, sera were evaluated for adipokines such as adiponectin, leptin and visfatin and inflammatory markers. Diet induced systemic changes were also analysed using a fatty liver score and evaluation of crown-like structures (CLS) in adipose tissue. OA progression was scored and quantified based on histological stainings of the joints (H/E, safranin O). Immunohistochemical stainings of the joints were performed to evaluate local distribution of adipokine positive cells and the respective cell types. Metabolic parameters were correlated to the local progression of OA. Results: The numbers of CLS were significantly lower comparing HFD (0.2±0.1553, n=7) with ND (5.219±0.9831, n=8) in mice. Fatty-liver score was significantly higher in HFD compared to ND. OA induction was significant at every timepoint vs healthy control and higher in HFD (e.g.: OA score at 6 weeks HFD 3.7 vs ND 1.4). In the OA groups, there was a positive correlation between bodyweight and OA score (r²=0.33). Correlation level of OA score with liver score or serum leptin level was low, even though leptin was significantly induced by HFD. However, DMM decreased leptin levels at all time points, independent from diet (e.g. 4 weeks: HFD healthy 18.4 ng/ml vs HFD DMM 3.7 ng/ml). The different parameters for metabolic changes (fatty liver score and bodyweight) were positively correlated with serum leptin level. HFD, DMM or the combination of both did not show significant effects on serum levels of adiponectin, visfatin or IL-6. Local adipokine secretion in the joints was independent from systemic metabolism parameters. Conclusions: Our data show that similar to observations in humans, OA is deteriorated by HFD which correlates mainly with the bodyweight and to a lower extend with metabolic changes induced by obesity. Local adipokine expression was especially detectable in the damaged menisci showing increased amounts of adiponectin and leptin producing cells. Interestingly, local adipokine expression was independent from systemic adipokine levels. Disclosure of Interest: None declared