Epigallocatechin-3-gallate diminishes cytokine-stimulated Cyr61 expression in human osteoblastic cells: A therapeutic potential for arthritis
Journal
Rheumatology (United Kingdom)
Journal Volume
51
Journal Issue
11
Pages
1953-1965
Date Issued
2012
Author(s)
Wu P.-H.
Hou K.-L.
EDDIE HSIANG HUA LAI
Wang J.-S.
Hong C.-Y.
Abstract
Objective: To assess the effects of epigallocatechin-3-gallate (EGCG) on cytokine-induced Cyr61 synthesis in human osteoblastic cells and the associated signalling pathways. The therapeutic effect of EGCG on CIA in rats was also studied.Methods: The expression of Cyr61 and NF-κB pathway molecules was examined by western blotting. CCL2 expression was assessed by northern blotting and ELISA. Interaction between NF-κB and Cyr61 promoter was evaluated by electrophoretic mobility shift assay. In rat CIA, osteoblastic expression of Cyr61 was examined by immunohistochemistry and disease progression was assessed by clinical, radiographic and histological examinations.Results: EGCG inhibited Cyr61 expression stimulated by cytokines in primary human osteoblasts and human osteoblastic cell line U2OS. In U2OS, oncostatin M (OSM) induced IκB-α degradation through the mTOR/rictor/Akt pathway, and EGCG attenuated the action. Electrophoretic mobility shift assay revealed that the OSM-enhanced NF-κB/DNA binding was reduced by EGCG, possibly through abrogating nucleus localization of p65 and p50. Cyr61 enhanced OSM-induced expression of CCL2. Moreover, EGCG diminished OSM-stimulated CCL2 expression at least partially via suppressing Cyr61 induction. Co-distribution of CD68+ macrophages and Cyr61+ osteoblasts in osteolytic areas was obvious in the CIA model. Clinical, radiographic and immunohistochemical analyses revealed that administration of EGCG markedly diminished the severity of CIA, macrophage infiltration, and the number of Cyr61-synthesizing osteoblasts.Conclusion: By modulating the mTOR/rictor/Akt/NF-κB pathway, EGCG attenuated Cyr61 production in osteoblastic cells and in turn diminished macrophage chemotaxis. Our data support the therapeutic potential of EGCG on arthritis. ? The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
SDGs
Other Subjects
cysteine rich protein 61; epigallocatechin gallate; I kappa B alpha; immunoglobulin enhancer binding protein; monocyte chemotactic protein 1; oncostatin M; protein p50; synaptotagmin I; animal experiment; arthritis; article; cell infiltration; controlled study; disease course; electrophoretic mobility; enzyme linked immunosorbent assay; histopathology; human; human cell; immunohistochemistry; male; nonhuman; Northern blotting; osteoblast; priority journal; protein expression; rat; signal transduction; Western blotting; Adult; Animals; Arthritis; Catechin; Cells, Cultured; Chemokine CCL2; Chromones; Cysteine-Rich Protein 61; Cytokines; Enzyme Inhibitors; Humans; Inositol Phosphates; Male; Morpholines; NF-kappa B; Osteoblasts; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Young Adult
Type
journal article