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  • Eplerenone treatment alleviates the development of joint lesions in a new rat model of spontaneous metabolic-associated osteoarthritis

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Eplerenone treatment alleviates the development of joint lesions in a new rat model of spontaneous metabolic-associated osteoarthritis
  1. Chaohua Deng1,2,
  2. Arnaud Bianchi1,2,
  3. Nathalie Presle1,2,
  4. David Moulin1,2,3,
  5. Meriem Koufany1,2,
  6. Cécile Guillaume1,2,
  7. Hervé Kempf1,2,
  8. Anne Pizard2,3,4,5
  1. 1 UMR7365 CNRS-Université de Lorraine, IMoPA, Ingénierie Moléculaire et Physiopathologie Articulaire, Vandoeuvre-les-Nancy, France
  2. 2 Fédération de Recherche 3209, Vandoeuvre-les-Nancy, France
  3. 3 CHRU Nancy, Vandoeuvre-les-Nancy, France
  4. 4 CIC-P1433 Inserm, CHRU Nancy, Vandoeuvre-les-Nancy, France
  5. 5 UMRS-Inserm U1116, Université de Lorraine, Vandoeuvre-les-Nancy, France
  1. Correspondence to Dr Hervé Kempf, UMR 7365 CNRS-UL, IMoPA, 9 avenue de la Forrêt de Haye, Vandoeuvre-lès-Nancy 54500, France; herve.kempf{at}inserm.fr and Dr Anne Pizard, UMRS-Inserm U1116, CHRU Nancy, ILCV, 4 rue du Morvan, Vandoeuvre-les-Nancy 54500, France; anne.pizard{at}inserm.fr

https://doi.org/10.1136/annrheumdis-2016-210700

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    Increasing epidemiological and clinical studies suggest that metabolic syndrome (MetS) plays a role in the incidence and progression of osteoarthritis (OA).1 2 However, in absence of an appropriate MetS-associated OA experimental model,3 the MetS contribution to the joint phenotype in OA remains difficult to investigate and the evaluation of potential disease-modifying OA drugs (DMOADs) is complicated. Noteworthy, in contrast to their lean SHHF+/+(spontaneously hypertensive heart failure) controls, obese SHHFcp/cp rats, a well-characterised model of MetS,4 develop drastic metabolic, cardiovascular and renal alterations that are substantially improved through an early chronic mineralocorticoid receptor antagonism (MRA) treatment.5 Thus, by comparing young (1.5 months) and aged (12.5 months) lean SHHF+/+ and obese SHHFcp/cp rats, we sought to evaluate for the first time the potential (1) contribution of MetS to joint alterations and (2) therapeutic benefits derived from chronic MRA treatment by eplerenone (figure 1A).

    Figure 1

    Preventive 11-month treatment with mineralocorticoid receptor antagonist eplerenone alleviated the metabolic syndrome (MetS)-associated joint lesions in SHHF model. (A) Experimental design of the study. Lean spontaneously hypertensive heart failure (SHHF+/+) and obese SHHFcp/cp rats were divided randomly into treatment groups. Untreated groups (n=4 for SHHF+/+ and n=4 for SHHFcp/cp) were given …

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    Footnotes

    • HK and AP both contributed equally as senior authors.

    • Contributors HK and AP conceived the study.

      CD, AB, NP, DM, MK, CG and AP performed the experiments.

      CD, AB, NP, DM, MK, HK and AP interpreted the data.

      CD, HK and AP wrote the manuscript.

    • Funding This work was supported by Inserm and Région Lorraine. CD was funded by a China Scholarship Council graduate scholarship.

    • Disclaimer The sponsors had no role in any experimental part of the study or the writing of the manuscript.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators AP and HK are joint senior authors.

    • Correction notice This article has been corrected since it published Online First. The joint author statement for AP and HK has been added and the order of the authors updated.