(-)-Epigallocatechin gallate but not chlorogenic acid upregulates osteoprotegerin synthesis through regulation of bone morphogenetic protein-4 in osteoblasts

Fujita,Kazuhiko; Otsuka,Takanobu; Yamamoto,Naohiro; Kainuma,Shingo; Ohguchi,Reou; Kawabata,Tetsu; Sakai,Go; Kuroyanagi,Gen; Matsushima‑Nishiwaki,Rie; Kozawa,Osamu; Tokuda,Haruhiko

doi:10.3892/etm.2017.4491

(-)-Epigallocatechin gallate but not chlorogenic acid upregulates osteoprotegerin synthesis through regulation of bone morphogenetic protein-4 in osteoblasts

Authors:
- Kazuhiko Fujita
- Takanobu Otsuka
- Naohiro Yamamoto
- Shingo Kainuma
- Reou Ohguchi
- Tetsu Kawabata
- Go Sakai
- Gen Kuroyanagi
- Rie Matsushima‑Nishiwaki
- Osamu Kozawa
- Haruhiko Tokuda
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan
Published online on: May 22, 2017 https://doi.org/10.3892/etm.2017.4491
Pages: 417-423

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Abstract

Chlorogenic acid (CGA) is a primary phenolic component of coffee and (‑)‑epigallocatechin gallate (EGCG) is a primary flavonoid component of green tea, both of which have been documented to possess beneficial health properties. A previous study by the present authors demonstrated that p38 mitogen‑activated protein kinase (MAPK) may be associated with osteoprotegerin synthesis stimulated by bone morphogenetic protein‑4 (BMP‑4) in osteoblast‑like MC3T3‑E1 cells. In the present study, the effects of CGA and EGCG on BMP‑4‑stimulated osteoprotegerin synthesis in MC3T3‑E1 cells were investigated. It was observed that CGA had no effect on osteoprotegerin release stimulated by BMP‑4, whereas EGCG significantly enhanced BMP‑4‑stimulated osteoprotegerin release (P=0.003). Levels of osteoprotegerin mRNA expression induced by BMP‑4 were also significantly increased by EGCG (P=0.03). By contrast, EGCG had no significant effect on phosphorylation of Smad1 or p38 MAPK induced by BMP‑4. In addition, EGCG had little effect on BMP‑induced phosphorylation of p70 S6 kinase; however rapamycin, as an inhibitor of p70 S6 kinase, significantly suppressed osteoprotegerin release (P=0.007). These data suggest that EGCG but not CGA may upregulate the synthesis of osteoprotegerin induced by BMP-4 in osteoblasts.

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