Repression of IGF-I-induced osteoblast migration by (-)-epigallocatechin gallate through p44/p42 MAP kinase signaling

Polyphenolic compounds in beverages may have benefits in the prevention of osteoporosis. It has been demonstrated previously that insulin-like growth factor-I (IGF-I) could stimulate the migration of osteoblasts. In the present study, it was investigated whether chlorogenic acid, a major polyphenol in coffee, and (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea, could affect this IGF-I-stimulated migration of osteoblast-like MC3T3-E1 cells. The IGF-I-stimulated osteoblast migration, evaluated by Transwell cell migration and wound-healing assays, was inhibited by EGCG but not chlorogenic acid. IGF-I induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase, p70 S6 kinase and Akt. The IGF-I-induced migration was suppressed by PD98059, a MAP kinase kinase 1/2 inhibitor, and deguelin, an Akt inhibitor, but not rapamycin, an inhibitor of the upstream kinase of p70 S6 kinase (mammalian target of rapamycin). EGCG attenuated the IGF-I-induced phosphorylation of p44/p42 MAP kinase but not Akt. Taken together, the present results suggest that EGCG inhibits IGF-I-induced osteoblast migration via p44/p42 MAP kinase.