Background/Purpose:

Adipocytokines are bioactive factors produced mainly by adipose tissue. They not only regulate energy homeostasis, but also influence immune responses. Osteoarthritis (OA) is one of the most common degenerative joint diseases whereas rheumatoid arthritis (RA) is a chronic autoimmune joint disease. Therefore, an obesity model (High-fat diet, HFD) was combined with a model for OA (DMM, destabilization of the medial meniscus) or a model for RA (collagen induced arthritis, CIA) to evaluate the role of the adipokines adiponectin, leptin and visfatin in these settings.

This work evaluates the influence of different adipokines and obesity on OA compared to RA regarding systemic vs. local effects at different time points.

Methods:

The OA model was performed in C57Bl/6 mice fed with HFD or ND (normal diet) prior to OA induction. The RA model was performed in DBA/1Rj mice fed with the same diets. Mice were sacrificed and analyzed 4, 6 and 8 weeks (OA model) or 4, 5.5 and 7 weeks (RA model) after induction of RA/OA. For systemic analysis, sera were evaluated for the adipokines adiponectin, leptin and visfatin and inflammatory markers. Diet induced systemic changes were analyzed using a fatty liver score and evaluation of crown-like structures (CLS) in adipose tissue. Histological scoring for OA and a clinical score for RA was performed. Immunohistochemical stainings of OA joints were performed to evaluate local adipokines and the producing cell types.

Results:

All three models in the respective combinations were successful, represented by histological destruction of the joints and increased fatty liver score (C57Bl/6) or bodyweight (DBA/1Rj). The number of CLS were significantly higher comparing HFD (0.2 ± 0.1553, n=7) with ND (5.219 ± 0.9831, n=8) in C57Bl/6 mice and fatty-liver score was significantly higher in HFD compared to ND in C57Bl/6 but not in DBA/1Rj. Leptin was significantly induced by HFD in both mouse strains, this effect could be annulled by leptin reducing effects of the CIA model. DMM reduced systemic leptin but with much weaker effect. HFD, DMM or the combination of both did not show significant effects on serum levels of adiponectin, visfatin or IL-6. However, in DBA/1Rj mice CRP was significantly induced by CIA. Local adipokine distribution in the joints after DMM surgery was independent from systemic metabolism parameters.

Conclusion:

Our data show that similar to observations in humans, OA is deteriorated by HFD which correlates mainly with the bodyweight. This phenomenon was not visible in our RA model. CIA and DMM both decreased systemic leptin, which was much more effective in CIA suggesting an inflammation-dependent mechanism. Interestingly, in OA the local adipokine expression was independent from systemic adipokine levels.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-metabolic-changes-in-osteoarthritis-and-rheumatoid-arthritis-mouse-models/