Article Text

OP0174 Ppar Gamma Deficient Mice Develop Spontaneous Polyarthritis
  1. M. Koufany1,
  2. F. Gilardi2,
  3. M. Schiffrin2,
  4. C. Winkler2,
  5. A. Bianchi1,
  6. J.-Y. Jouzeau1,
  7. B. Desvergne2,
  8. D. Moulin1
  1. 1IMoPA, UMR7365 CNRS-Université de Lorraine, Vandoeuvre les Nancy, France
  2. 2Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland


Background Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of transcription factors. PPARγ is involved in the regulation of adipocyte differentiation, glucose homeostasis and inflammation. Others and ourselves have previously demonstrated that PPARγ agonists could be successfully used in the treatment of experimental arthritis, representing an attractive potential approach for rheumatoid arthritis (RA) therapy. Indeed, we recently demonstrated that treatment with synthetic agonist of PPARγ isotype (pioglitazone) in addition to decrease arthritis severity, specifically reduced inflammatory-bone destruction and protected bone micro-architecture in experimental arthritis by controlling circulating and local expression of Interleukin-(IL-)17 with a subsequent decrease of the (RANKL/OPG) ratio [1]. Furthermore, recent genetic studies have demonstrated an association between a known coding SNP in the PPARG gene and psoriatic [2] or rheumatoid arthritis [3]. In recent clinical studies, a PPARγ agonist, used alone or in combination with NSAIDs or methotrexate appears to represent a promising therapeutic strategy for rheumatoid or psoriatic arthritis patients [4].

Objectives This study aims to characterize the articular phenotype of PPARγ deficient mice.

Methods Fully viable PPARγ-null mice were generated through specific and total epiblastic gene deletion using Sox2Cre/PPARγL2/L2 mice. Histologic examination of ankle and knee joints after specific staining of cartilage and synovium tissues was performed. Synovial mast cells were specifically stained with toludine blue. Finally, serum levels of the pro-inflammatory cytokines IL-17 and TNFα, the anti-inflammatory/immunomodulatory cytokine IL-10 and the chemokine KC were determined using multiplex cytokine ELISA.

Results We have observed that adult PPARγ–/– mice show evidence of arthritis in the ankle and knee with 100% incidence. We have determined the onset of the disease around 3 weeks of age. Joints share many histological features with RA, such as synovial lining hyperplasia, synovial hypervascularization, infiltrating immune cells, cartilage erosion and bone remodeling (Figure 1: Safranin O- Fast Green (A) and Hematoxylin-Eosin (B) staining of knee joint sections of wild type and PPARγ–/– littermates showing evidence of severe arthritis in PPARγ deficient mice: cartilage (black arrow) and bone erosion (red arrow) (A), synovial lining hyperplasia (yellow arrow), synovial hypervascularization (blue arrow), infiltrating immune cells (green arrow) (B). We explored concomitantly the circulating levels of several cytokines in these mice. We found notably elevated levels of the pro-inflammatory cytokines IL-17 and TNFα, the chemokine KC and reduced levels of the anti-inflamatory/immunomodulatory cytokine IL-10. Of major interest, we observed a great increased number (more than 50 fold) of mast cells in the synovium of PPARγ–/– mice, as compared to heterozygous or wild type littermates.

Conclusions Taken together these data suggest that PPARγ may be a key regulator of arthritis development in mice. We described here a new model of spontaneous polyarthritis in mice.


  1. Arthritis Rheum. 2013 Dec;65(12):3084-95.

  2. Ann Rheum Dis. 2012 Feb;71(2):313-4.

  3. Rheumatol Int. 2013 Apr 30.

  4. J Am Heart Assoc. 2013 Nov 19;2(6):e000441.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3291

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.