Objectives. To evaluate the contribution of leptin, an adipose-derived hormone, to the pathophysiology of osteoarthritis (OA), by determining leptin in both synovial fluid and cartilage specimens from human joints, and by investigating the effect on cartilage of intra-articular injection of leptin in rat.

Methods. Leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) in synovial fluids sampled from OA patients undergoing either knee replacement surgery or knee arthroscopy. Besides, histological sections of articular cartilage and osteophytes obtained during surgery for total knee replacement, were graded using the Mankin score, and were immunostained using antibodies to leptin, TGF_ and IGF-1. For experimental studies, various doses of leptin (10, 30, 100 and 300μg) were injected into the rat knee joint. Tibial plateaus were collected and further processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (Ob-Rb), and growth factors by RT-PCR and immunohistochemistry.

Results. Leptin was found in synovial fluids from human OA-affected joints, and concentrations were correlated to Body Mass Index. A marked expression of the protein was seen in OA cartilage and in osteophytes, while few chondrocytes produced leptin in normal cartilage. Furthermore, the pattern and level of leptin expression were related to the grade of cartilage destruction, and paralleled those of growth factors (IGF-1 and TGFb-1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes, and induced the synthesis of IGF-1 and TGFb-1 in cartilage at both mRNA and protein levels.

Conclusion. These findings provide a new peripheral function to leptin as a key regulator of chondrocytes metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.