Epigallocatechin‐3‐gallate diminishes CCL2 expression in human osteoblastic cells via up‐regulation of phosphatidylinositol 3‐Kinase/Akt/Raf‐1 interaction: A potential therapeutic benefit for arthritis

Abstract

Objective. To assess the effects of epigallocatechin-3-gallate (EGCG) on oncostatin M (OSM)-induced CCL2 synthesis and the associated signaling pathways in human osteoblastic cells. The therapeutic effect of EGCG on collagen-induced arthritis (CIA) in rats was also studied.Methods. CCL2 and c-Fos messenger RNA expression was analyzed by Northern blotting. The modulating effects of EGCG on the activation of Raf-1, Akt, and phosphatidylinositol 3-kinase (PI 3-kinase) were examined by coimmunoprecipitation, Western blotting, and PI 3-kinase activity assay. Interactions between c-Fos and CCL2 promoter were evaluated by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. The effect of EGCG on CIA in rats was examined clinically and immunohistochemically.Results Conclusion. By stimulating PI 3-kinase activity, EGCG promoted Akt/Raf-1 crosstalk, resulting in decreased AP-1 binding to CCL2 promoter, and finally reduced CCL2 production in osteoblasts. EGCG alleviated the severity of CIA, probably by suppressing CCL2 synthesis in osteoblasts to diminish macrophage infiltration. Our data support the therapeutic potential of EGCG on arthritis.

Epigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse mesangial cells

“…55 There have been mixed reports regarding the effects of EGCG on Akt depending on the cell type studied, as EGCG is shown to reduce Akt phosphorylation in endothelial cells, tumor associated endothelial cells and caco-2 cells, [56][57][58][59] but activate Akt in lung carcinoma cells and osteoblasts. 60,61 Here, we show that EGCG reduces Akt activation and subsequently inflammation in immune stimulated mesangial cells.…”

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

“…Primary cultures of human bone marrowderived osteoblasts were established from alveolar bone explants as previously described (30). Cells were maintained in induction media for the duration of the study, without serum starvation.…”

“…ChIP was performed as described previously (30), using an assay kit from Upstate Biotechnology. Briefly, the DNA-protein complex from treated U2OS cells was crosslinked with 1% formaldehyde for 10 minutes at room temperature.…”

Regulation of cartilage and inflammatory biomarkers in rheumatoid arthritis patients treated with green tea therapy

“…The data obtained showed a significant correlation between the decrease in the levels of CRP, ESR, Rf, IL-6 and TNF-α in good and moderate green tea RA responders as compared to nonresponders, whereas the disease activity remained unchanged. These results demonstrated the antirheumatic activity of green tea which may be related to the antioxidant and anti-inflammatory of its phenolic compounds, especially catechins (Morinobu et al, 2008;Lin et al, 2008). Also, many studies reported that treatment of green tea reduced oxidative stress free radicals induced production of proinflammatory cytokines TNF-α, IL-6, CRP and NF-kB activation in a dose dependent manner (Kim et al, 2000;Wahyudi and Sargowo, 2007;Ramesh et al, 2009).…”