Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
Mol Med Rep. 2017 Nov;16(5):6376-6381. doi: 10.3892/mmr.2017.7354. Epub 2017 Aug 24.
(‑)‑Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), major flavonoids in green tea, and coffee, respectively, are recognized as possessing potential benefits in a multitude of human health conditions, including bone disorders. We have previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of osteoprotegerin (OPG) through the activation of p44/p42 mitogen‑activated protein kinase (MAPK), p38 MAPK and stress activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in osteoblast‑like MC3T3‑E1 cells. In the present study, the effects of EGCG and CGA on PGF2α‑stimulated OPG synthesis in MC3T3‑E1 cells were investigated. EGCG significantly upregulated PGF2α‑stimulated OPG release, whereas CGA did not affect OPG release. The PGF2α‑induced expression level of OPG mRNA was enhanced by EGCG. Regarding the intracellular signaling underlying the effect of EGCG, EGCG failed to affect PGF2α‑stimulated phosphorylation of p44/p42 MAPK, p38 MAPK or SAPK/JNK. EGCG by itself markedly induced the phosphorylation of p44/p42 MAP kinase for up to 10 min and the status decreased subsequently, whereas EGCG did not significantly affect the phosphorylation status of p38 MAPK or SAPK/JNK within 60 min. These results indicated that EGCG, but not CGA amplifies the PGF2α‑stimulated OPG synthesis in osteoblasts.
(-)-表没食子儿茶素没食子酸酯(EGCG)和绿原酸(CGA)分别是绿茶和咖啡中的主要类黄酮,被认为具有多种人类健康状况的潜在益处,包括骨骼疾病。我们之前已经证明,前列腺素 F2α(PGF2α),一种有效的骨重塑介质,通过激活成骨细胞样 MC3T3-E1 细胞中的 p44/p42 丝裂原激活蛋白激酶(MAPK)、p38 MAPK 和应激激活蛋白激酶/c-Jun N-末端激酶(SAPK/JNK),刺激骨保护素(OPG)的合成。在本研究中,研究了 EGCG 和 CGA 对 MC3T3-E1 细胞中 PGF2α 刺激的 OPG 合成的影响。EGCG 显著上调 PGF2α 刺激的 OPG 释放,而 CGA 不影响 OPG 释放。EGCG 增强了 PGF2α 诱导的 OPG mRNA 的表达水平。关于 EGCG 作用的细胞内信号通路,EGCG 未能影响 PGF2α 刺激的 p44/p42 MAPK、p38 MAPK 或 SAPK/JNK 的磷酸化。EGCG 本身在长达 10 分钟内显著诱导 p44/p42 MAP 激酶的磷酸化,随后状态降低,而 EGCG 在 60 分钟内对 p38 MAPK 或 SAPK/JNK 的磷酸化状态没有显著影响。这些结果表明,EGCG 而不是 CGA 增强了成骨细胞中 PGF2α 刺激的 OPG 合成。