Adipocytokines in an Osteoarthritis Mouse Model

Marie-Lisa Hülser¹, Carina Schreiyäck¹, Yubin Luo², Aline Bozec², Georg Schett³, Elena Neumann⁴ and Ulf Müller-Ladner⁵, ¹Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany, Bad Nauheim, Germany, ²Department Clinic of Medicine 3 - Immunology und Rheumatology, University of Erlangen-Nürnberg, Department Clinic of Medicine 3 - Immunology and Rheumatology, Erlangen, Germany, Erlangen, Germany, ³Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany., Erlangen, Germany, ⁴Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany, Bad Nauheim, Germany, ⁵Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany, Bad-Nauheim, Germany

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Adipocytokines, mouse model and osteoarthritis

Session Information

Date: Tuesday, November 7, 2017

Title: Biology and Pathology of Bone and Joint Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

In the Western society adiposity and metabolic syndrome are an increasing field of medical research. Both entities influence the expression of adipokines such as adiponectin, visfatin or leptin, which also modulate the progress of osteoarthritis (OA).

To evaluate these comorbidities together, we combined a high-fat diet (HFD) with the DMM mouse model (destabilization of the medial meniscus). The serologic and local effects of HFD at different states of OA development were correlated to local/systemic adipokine expression.

Methods:

HFD and ND (normal diet) as control were fed to male C57Bl/6 mice for 3 months followed by surgical DMM (time point 0). Joints, organs and sera were collected 4, 6, and 8 weeks after surgery. Concentrations of the adipocytokines leptin, visfatin, adiponectin and IL-6 in the sera were measured by ELISA. Liver fat was scored to show metabolic changes. Arthritis progression was scored and quantified using histologic stainings of the joints (H/E, safranin O, Pappenheim and Masson-Goldner’s trichrome). Immunohistochemical stainings of the mouse joints were performed to evaluate the local distribution of adipokines. Adipokine levels were correlated to arthritis scores, fatty liver score and bodyweight.

Results:

At all time points, OA was significantly induced, especially by HFD compared to ND (e.g.: OA score at 6 weeks HFD 3.7 vs. ND 1.4). Systemically, leptin levels were significantly higher in HFD compared to ND, but DMM decreased leptin levels at all time points independent from diet (e.g. 4 weeks: HFD healthy 18.4 ng/ml vs. HFD DMM 3.7ng/ml). Systemic leptin levels correlate with liver fat content. Interestingly, the systemic changes of adiponectin by DMM were only present at week 8 (HFD healthy 5176ng/ml vs. HFD DMM 6149ng/ml). The combination of HFD and DMM did not show significant effects on serum levels of adiponectin, visfatin or IL-6 in this experimental setting. Local adipokine expression in the joints was independent from systemic adipokine levels.

Conclusion:

The data show that similar to the human setting, OA in the DMM model is deteriorated by HFD. This is serologically reflected by reduced protective leptin levels but not increased proinflammatory visfatin or adiponectin supporting the idea of a prominent local rather than systemic pathophysiology.

Disclosure: M. L. Hülser, None; C. Schreiyäck, None; Y. Luo, None; A. Bozec, None; G. Schett, None; E. Neumann, None; U. Müller-Ladner, None.

To cite this abstract in AMA style:

Hülser ML, Schreiyäck C, Luo Y, Bozec A, Schett G, Neumann E, Müller-Ladner U. Adipocytokines in an Osteoarthritis Mouse Model [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/adipocytokines-in-an-osteoarthritis-mouse-model/. Accessed .

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