S131advanced OA cartilage correlated significantly with BMI values of the patients (r=0.610,p<0.05).SF had higher leptin concentrations than the paired serum sample, while a significant correlation was observed between serum and SF leptin levels (r=0.672,p<0.01).In normal chondrocytes cultures (48 hrs), leptin enhanced cell proliferation but reduced it in osteoarthritic chondrocytes, while in long term cultures leptin had a similar detrimental effect on chondrocytes.Furthermore, leptin induced the production of IL-1β in long term cultures.Conclusions: For the first time to our knowledge, using quantitative real-time PCR, we observed leptin and Ob-Rb mRNA expression in chondrocytes of osteoarthritic cartilage.The observed intrajoint difference in leptin and Ob-Rb mRNA expression between advanced and minimally affected knee and hip osteoarthritic cartilage, along with the higher observed leptin concentrations in SF than in paired serum samples indicate a local role of leptin in joint tissues.The increased leptin's mRNA expression in obese compared to normal weight patients suggested that mechanical overload may alter chondrocytes' phenotype.Also the decrease in chondrocyte's proliferation after induction with leptin points toward a long term detrimental effect on cartilage, while the observed IL-1β production suggests an inflammatory role of leptin, which may account for cartilage degradation.Taken together our findings support the hypothesis that leptin is involved in OA development and that may be the missing link between biomechanical and metabolic factors involved in OA.However, further studies are needed to confirm the involvement of leptin in OA and to investigate the link between obesity, inflammation, leptin and osteoarthritis.