ROLE OF LEPTIN IN THE PATHOGENESIS OF OSTEOARTHRITIS: A CLINICAL AND EXPERIMENTAL STUDY

Abstract

Purpose of the study: This study was designed to assess the role of leptin in the development of osteoarthritis (OA) by searching for its presence in the synovial fluid (SF), tissues, and cartilage of osteoarthritic joints in humans and by observing the effect of intra-articular injections of leptin in the rat.

Material and methods: The leptin level in SF was measured (ELISA) in twenty patients (ten female, ten male, mean age 70 years). Presence of leptin, TGF beta and IGF1 in cartilage (and osteophytes) was detected by immunohistochemistry after histological evaluation (Mankin). In the rat, leptin was injected into the knee joint at the dose of 30 and 100 μg. After the immunohistological study, proteoglycan synthesis was assessed (S35 integration) as was the expression of leptin, TGF beta1 and IGF1 using RT-PCR.

Results: This study demonstrated for the first time the presence of leptin in synovial fluid (0.6–17.4 and 5.3–28.4 μg in male and female specimens respectively). There was a significant correlation with body mass index. Leptin was over expressed in chondrocytes of osteoarthritic cartilage and was correlated with the histological score (leptin not detecable in normal cartilage). IGF1 and TGF beta1 were expressed in osteoarthritic chondrocytes. The topographic distribution and the intensity of labeling varied with the histological score. There was a strong expression of TGF beta 1 only in osteophytes. In the rat, leptin stimulated anabolic functions of the chondrocyte: maximal effect at 30 μg (medial tibial plateau) and 100 μg (lateral tibial plateau). Leptin over expressed transcripts IGF 1 and TGF beta 1. This effect was confirmed at the protein level.

Discussion: Leptin is an adipocytokin which regulates food intake and energy expenditure at the hypothalamic level. A mechanical mechanism is the primary explanation of osteoarthritis in weight-bearing joints in obese patients. But leptin is also present specifically in non-weight-bearing joints in obese subjects. A biological factor is thus incriminated which might be leptin produced by adipose tissue. Leptin is overexpresssed in the cartilage of the osteoarthritic knee. This is in favor of a role for leptin in the pathogenesis of OA via synthesis of TGF beta 1 and IGF 1. This effect of leptin could explain the relationship between body mass index and the risk factor for osteoarthritis.