(‐)‐Epigallocatechin Gallate Reduces Platelet‐Derived Growth Factor‐BB‐Stimulated Interleukin‐6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

Abstract

We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptor β was not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.

Green tea and exercise interventions as nondrug remedies in geriatric patients with rheumatoid arthritis

“…The bioactive components in tea may benefit bone health in terms of maintaining a higher bone mineral density57, 58 ) . Furthermore, green tea or its bioactive EGCG component has been shown to reduce RA via an improvement in the bone resorption process, which ultimately reduces the release of both NTX and DPD in serum or urine samples59,60,61 ) . The high EGCG contents of our green tea extract were shown to be responsible for the anti-rheumatic and other biological activities of green tea, and EGCG possesses about 25–100 times more antioxidant potential than vitamins C and E62,63,64 ) .…”

Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model☆☆☆

“…Both epidemiological [22][23][24][25], animal [10,11] and cellular [26][27][28] studies strongly suggested that green tea polyphenols (GTP, green tea extract) are a promising dietary antioxidant for preventing bone loss in women and men with low bone mass [21]. In addition, our recent study shows that drinking water supplemented with GTP mitigated bone loss due to an increase of antioxidant capacity in conjunction with a decrease in oxidative stress damage [10].…”

Green tea and bone metabolism

“…The Wnt pathway is now known to control bone development and bone mass acquisition at all skeletal sites [130, 131], and Wnt signaling drives differentiation of osteo-chondrogenic progenitor cells toward the osteoblast lineage. When the Wnt ligand binds to its receptor (Frizzled) and co-receptor (low-density lipoprotein receptor-related protein [LRP)5/6] [160-162], the signal turns on the Wnt pathway [133], giving the power of Wnt signaling to stimulate osteoblastic differentiation.…”

“…These same authors [159] also reported that EGCG inhibits basic-fibroblast-growth-factor-2-induced IL-6 synthesis at least partly via attenuation of the p44/p42 MAP kinase pathway and the p38 MAP kinase pathway in osteoblasts. Takai et al [160] found that EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression induced by platelet-derived growth factor-BB through suppression of the SAPK/JNK pathway in osteoblast-like MC3T3-E1 cells. Moreover, Ishida [161] reported that EGCG controls inflammatory bone resorption in chronic osteomyelitis by inhibiting the production of IL-6 and RANKL in osteoblasts infected with S. aureus .…”