THU0068 COMPARISON OF INFLAMMATION DURING METABOLIC CHANGES IN RHEUMATOID AND OSTEOARTHRITIS MOUSE MODELS
Authors: H. M. Sauermilch, M. L. Hülser, C. Schreiyäck, Y. Luo, A. Bozec, G. Schett, U. Müller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2020)

Background: Arthritis is influenced by metabolic changes. Adipokines are bioactive factors produced by adipose tissue with important effects on energy homeostasis and immune responses but are also involved in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Objectives: To evaluate inflammation during metabolic and adipokine induced changes in experimental models of RA and OA at different time points, an obesity model (high-fat-died, HFD) was therefore combined with an OA (DMM, destabilization of the medial meniscus) and RA (collagen induced arthritis, CIA) mouse model. Methods: Mice were fed with HFD or ND (normal diet) for 12 (OA) or 6 (RA) weeks prior to arthritis induction. DMM was performed in C57Bl/6 mice and CIA was induced in DBA/1Rj mice. After 4, 6 and 8 (DMM) or after 4, 5 and 7 weeks (CIA) of arthritis induction animals were sacrificed to collect histological and serological data. Clinical scoring for CIA and histological scorings for both models were performed to evaluate disease development and progression. Diet-induced effects were monitored by weight, fatty liver score and crown-like structures (CLS) counts in adipose tissue. To evaluate HFD-induced adipokine levels adiponectin, leptin and visfatin serum concentrations were measured in parallel to the CRP. Local tissue adipokine expression was evaluated by immunohistochemistry. Results: Induction of OA and RA was successful in an HFD setting, shown by histological joint destruction and the increased fatty liver score and bodyweight. Compared to healthy animals, CRP levels were significantly increased after CIA induction, confirming systemic inflammation. In DMM, the number of CLS were significantly higher in HFD (0.2 ± 0.16, n=7) compared to ND (5.2 ± 0.98, n=8). No difference was found in CIA-severity between HFD and ND. However, CIA induction increased the number of CLS in HFD (2.77 ± 1.07, n=6) and interestingly in ND animals (8.14 ± 0.23, n=5) compared to healthy ND (0.45 ± 0.03, n=4) and healthy HFD mice (2.57 ± 0.53, n=4) without CIA. As expected, HFD led to a significant increase in systemic leptin in healthy animals in both models. Interestingly, CIA and DMM induction decreased systemic leptin levels significantly in ND and HFD, which was more prominent in CIA. The systemic effect was not reflected by local leptin distribution in the joints (CIA) which were not altered by diet. 5. and 7 weeks after CIA induction HFD led to a reduction in local adiponectin and visfatin expression, which were not reflected in systemic levels. Conclusion: The data show that HFD deteriorates OA, which is similar to observations in humans. In contrast, HFD induction showed no significant difference in CIA severity compared to ND. Furthermore, CIA reduced local adipokine expression under HFD at later time points but not under ND. According to high numbers of CLS in ND/CIA animals and the strong reduction of leptin in CIA with HFD, CIA onset and severity seems to be obesity independent and more dependent on inflammation while OA appears to be directly influenced by obesity. However, HFD-induced obesity seems to alter local and systemic adipokine expression also in CIA. Interestingly, local adipokine distribution in affected joints was independent from systemic adipokine levels. Disclosure of Interests: Hani Manfred Sauermilch: None declared, Marie-Lisa Hülser: None declared, Carina Schreiyäck: None declared, Yubin Luo: None declared, Aline Bozec: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Ulf Müller-Ladner Speakers bureau: Biogen, Elena Neumann: None declared