IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity

Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients

Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis

Influence of alcohols on citric acid production by Aspergillus niger A-9 entrapped in polyacrylamide gels

In this study, the production of citric acid has been achieved by using Aspergillus niger conidiaspores, entrapped in polyacrylamide gels, and the factors that affect this production have been investigated. On citric acid production the effect of starting sucrose concentration (100-180 g/l), the initial nitrogen concentration (0-0.3 g/l), the effect of the methanol concentration in 100ml feeding medium (0-6 ml), and finally the effect of ethanol concentration (0-6 ml) in 100 ml feeding medium were studied and optimum experimental conditions were determined. As a result of the experiments, the starting nitrogen concentration (0.05 g/l) and the starting sucrose concentration (140 g/l) were optimized and maximum citric acid production was observed for the given conditions. On the other hand, the maximum citric acid production was observed by the addition of 4.0ml methanol and 3.0ml ethanol. (c) 2004 Published by Elsevier Ltd

The production of citric acid by using immobilized Aspergillus niger A-9 and investigation of its various effects

The production of citric acid was achieved by using Aspergillus niger conidiaspores, entrapped in Ca-alginate beads, and the factors that affect this production were investigated. The effects of starting sucrose concentration (100-180 g/l), nitrogen concentration (0-0.3 g/l), methanol concentration (0-6 ml) and finally ethanol concentration (0-5 ml) in 100 ml feeding medium on citric acid production were studied and optimum experimental conditions were determined. The starting nitrogen concentration (0.05 g/l) and the starting sucrose concentration (140 g/l) were optimized and maximum citric acid production observed under these given conditions. Maximum citric acid production was observed upon addition of 4.0 ml methanol and 3.0 ml ethanol