Leptin augments the inflammatory effect of Interleukin 1 Beta on synoviocytes mainly through NF-kB and STAT3 prompting its possible implementation in OA pathogenesis

Background Increasing evidences have shown high osteoarthritis (OA) incidence in both weight and non-weight bearing joints among obese patients. Since leptin level in synovial fluid of obese OA patients was elevated compared to that of healthy people, leptin may be a crucial contributing factor in pathogenesis of OA, especially for non-weight bearing joints, in obese patients. This study aimed to examine the effect of leptin on synovial inflammation in the presence or absence of IL-1β, known inducer of joint inflammation, and the plausible intracellular mechanisms in SW982 synoviocytes. Methods and results Leptin, in the physiological concentration, as low as 1 ng/mL, can induce the expression of inflammatory cytokines, IL-6 and IL-8, in synoviocytes by activating p65, p38, JNK, STAT1, and STAT3. In addition, the lowest pathological concentration of leptin can enhance the inflammatory effect of IL-1β resulting in significantly higher production of IL-6 and IL-8 via activation of p65 and STAT3, highlighting its role in pathogenesis of inflammation-related OA. Conclusions Our research discovered crosstalking of p65 and STAT3, it may have a significant role in the development of OA in the joints of obese people by enhancing inflammation through the activation of p65 and STAT3.