Leptin alone and in combination with interleukin-1-beta induced cartilage degradation potentially inhibited by EPA and DHA

<p>Osteoarthritis (OA) is the most common form of arthritis. Obesity has been believed to be an important risk factor for OA development and the progression of not only load-bearing joints, but low-load-bearing joints as well. Increased leptin has been the focus of a link between obesity and OA. In this study, the effects of pathological (100ng/ml) or supra-pathological (10μg/ml) concentrations of leptin alone or in combination with IL1β on cartilage metabolisms were studied in porcine cartilage explant. The involved mechanisms were examined in human articular chondrocytes (HACs). Moreover, the protective effect of omega-3 polyunsaturated acids, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was also investigated. Leptin (10μg/ml) alone or in combination with IL1β could induce cartilage destruction, although lower concentrations had no effect. Leptin activated NFκB, ERK, JNK and p38 in HACs, which led to the induction of MMP3, MMP13 and ADAMTS4 secretions. The combined effect could further induce those enzymes through the additive effect on activation of NFκB and JNK. Interestingly, both EPA and DHA could inhibit cartilage damage induced by leptin plus IL1β by reducing the activation of NFκB and JNK, which led to the decrease of ADAMTS4 secretion. Altogether, only a supra-pathological concentration of leptin alone or in combination with IL1β could induce cartilage destruction, whereas a pathological one could not. This effect could be inhibited by EPA and DHA. To gain greater understanding of the link between leptin and OA, the effect of different levels of leptin on several states of OA cartilage requires further investigation.</p

Additional file 1: of Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

LDH released from hSF and SW982 cells. Cell viability testing was performed by LDH measurement in culture medium. a. LDH released from hSF cells under TNF-α alone, sesamin alone or combination of TNF-α and sesamin. b. LDH released from SW982 cells under TNF-α alone, sesamin alone or combination of TNF-α and sesamin. Values are presented as mean ± SEM (n = 3). (PNG 135 kb