Epigallocatechin-3-gallate suppresses Oncostatin M-induced Chemokine expression in MG-63 human osteoblast-like cells: Implication of MAPK signaling pathway

• Main Authors: Flora Tzu-Chin Yeh, 葉子菁
• Other Authors: Wan-Hong Lan
• Format: Others
• Language: en_US
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/23173824754908905942

碩士 === 國立臺灣大學 === 臨床牙醫學研究所 === 90 === Oncostatin M (OSM) is capable of inducing monocyte chemoattractant protein-1 (MCP-1) expression in osteoblasts, resulting in inflammatory bone resorption and formation of periapical lesion. The purpose of this study was to investigate the signaling pathway employed by OSM to induce MCP-1 gene expression in osteoblasts, and the mechanisms by which epigallocatechin-3-gallate (EGCG) employed to inhibit the process. MG-63, a cell line of human osteosarcoma, was used in the present study. Western blot analysis showed that OSM activated MAPK pathway via inducing phosphorylation of MEK 1/2. Northern blot analysis showed that OSM induced MCP-1 gene expression in MG-63, whereas PD-98059 could inhibit this process. OSM also stimulated c-Fos expression and curcumin abolished the OSM-induced MCP-1 expression. EGCG inhibited the phosphorylation of MEK/ERK induced by OSM. Furthermore, concerning the activity of the more upstream signaling molecule: Raf-1, immunoprecipitation study revealed that EGCG abolished dephosphorylation of Ser 259 and phosphorylation of Ser 338 triggered by OSM. At the level of nuclear transcription, electrophoretic mobility shift assay (EMSA) revealed that EGCG inhibited the OSM-stimulated AP-1/DNA binding in MG-63. In conclusion, EGCG inhibits OSM-induced AP-1/DNA binding by modulating the phosphorylation of Raf-1 (Ser 259, Ser 338) and the MEK/ERK MAPK signaling pathways, resulting in the down-regulation of MCP-1 gene expression in MG-63.