Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis

Stéphane Pallu1, Pierre-Jean Francin2, Cécile Guillaume2, Pascale Gegout-Pottie2, Patrick Netter2, Didier Mainard2, Bernard Terlain2 and Nathalie Presle2*

Author Affiliations

1 UMR S658 INSERM, Hôpital Porte Madeleine, 1 Rue Porte Madeleine, BP 2439, 45032 Orléans, France

2 UMR CNRS-UHP 7561, Faculté de Médecine, Avenue de la forêt de Haye, BP 184, 54505 Vandoeuvre-les-Nancy, France

For all author emails, please log on.

Arthritis Research & Therapy 2010, 12:R112  doi:10.1186/ar3048

Published: 9 June 2010

Abstract

Introduction

Increasing evidence support the regulatory role of leptin in osteoarthritis (OA). As high circulating concentrations of leptin disrupt the physiological function of the adipokine in obese individuals, the current study has been undertaken to determine whether the elevated levels of leptin found in the joint from obese OA patients also induce changes in the chondrocyte response to leptin.

Methods

Chondrocytes isolated from OA patients with various body mass index (BMI) were treated with 20, 100 or 500 ng/ml of leptin. The expression of cartilage-specific components (aggrecan, type 2 collagen), as well as regulatory (IGF-1, TGFβ, MMP-13, TIMP 2) or inflammatory (COX-2, iNOS, IL-1) factors was investigated by real-time PCR to evaluate chondrocyte responsiveness to leptin. Furthermore, the effect of body mass index (BMI) on leptin signalling pathways was analyzed with an enzyme-linked immunosorbent assay for STATs activation.

Results

Leptin at 20 ng/ml was unable to modulate gene expression in chondrocytes, except for MMP-13 in obese OA patients. Higher leptin levels induced the expression of IGF-1, type 2 collagen, TIMP-2 and MMP-13. However, the activity of the adipokine was shown to be critically dependent on both the concentration and the BMI of the patients with a negative association between the activation of regulated genes and BMI for 100 ng/ml of adipokine, but a positive association between chondrocyte responsiveness and BMI for the highest leptin dose. In addition, the gene encoding MMP-13 was identified as a target of leptin for chondrocytes originated from obese patients while mRNA level of TIMP-2 was increased in leptin-treated chondrocytes collected from normal or overweight patients. The adipokine at 500 ng/ml triggered signal transduction through a STAT-dependent pathway while 100 ng/ml of leptin failed to activate STAT 3 but induced STAT 1α phosphorylation in chondrocytes obtained from obese patients.

Conclusions

The current study clearly showed that characteristics of OA patients and more expecially obesity may affect the responsiveness of cultured chondrocytes to leptin. In addition, the BMI-dependent effect of leptin for the expression of TIMP-2 and MMP-13 may explain why obesity is associated with an increased risk for OA.