Objective. To evaluate the contribution of leptin (an adipose tissue-derived hormone) to the pathophysiology of osteoarthritis (OA), by determining the level of leptin in both synovial fluid (SF) and cartilage specimens obtained from human joints. We also investigated the effect of leptin on cartilage, using intraarticular injections of leptin in rats.Methods. Leptin levels in SF samples obtained from OA patients undergoing either knee replacement surgery or knee arthroscopy were measured by enzymelinked immunosorbent assay. In addition, histologic 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, transforming growth factor ␤ (TGF␤), and insulin-like growth factor 1 (IGF-1). For experimental studies, various doses of leptin (10, 30, 100, and 300 g) were injected into the knee joints of rats. Tibial plateaus were collected and processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (ObRb), and growth factors by reverse transcriptasepolymerase chain reaction and immunohistochemical analysis.Results. Leptin was observed in SF obtained from human OA-affected joints, and leptin concentrations correlated with the body mass index. Marked expression of the protein was observed in OA cartilage and in osteophytes, while in normal cartilage, few chondrocytes produced leptin. 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 TGF␤1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes and induced the synthesis of IGF-1 and TGF␤1 in cartilage at both the messenger RNA and the protein levels.Conclusion. These findings suggest a new peripheral function of leptin as a key regulator of chondrocyte metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.

Objective. To characterize the doseresponsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats.Methods. Rat mobility was assessed by biotelemetry. Articular lesions were characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethylmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage.Results. Spontaneous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response). Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long-term loss of spontaneous mobility on day 15, when subchondral bone was exposed. These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg).Conclusion. When a suMicient dose of MIA is used, this model can easily and quickly reproduce OA-like lesions and functional impairment in rats, similar to that observed in human disease. These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or

These data demonstrated that adipokines serum levels are not predictive values for SF determination. The joint cavity is a special space where each adipokine undergoes specific regulatory pathways, strengthening the hypothesis that adipokines may have local effects in the joint and may account for the high prevalence of OA in women.

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