Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China.
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China.
Int Immunopharmacol. 2021 Jun;95:107464. doi: 10.1016/j.intimp.2021.107464. Epub 2021 Mar 4.
Consuming green tea has many health benefits, including regulating bone metabolism and ameliorating osteoporosis, mainly in older and postmenopausal women. This osteoprotective effect has been attributed to the biologically active polyphenol (-)-epigallocatechin-3-gallate (EGCG). Although EGCG inhibits osteoclastogenesis, its underlying molecular mechanism remains to be elucidated. Interaction between receptor activator of nuclear factor (NF)-κB ligand (RANKL) and RANK plays critical roles in the differentiation and activation of osteoclasts and is therefore considered a therapeutic target for osteoclast-related diseases such as osteoporosis. In the present study, we found that EGCG can bind directly to RANK and RANKL and interfere with their interaction, thereby suppressing RANKL-induced phosphorylation of IKKα/β, IκBα, p65, JNK, ERK1/2, and p38 and key downstream regulatory factors, including nuclear factor of activated T cell c1 (NFATc1), c-Fos, tartrate-resistant acid phosphatase (TRAP), c-Src, and cathepsin K, in osteoclast precursors. This can ultimately inhibit osteoclastogenesis. Taken together, our results show that EGCG can bind directly to RANK and RANKL and block their interaction and that, by inhibiting NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, it negatively regulates RANKL-induced osteoclastogenesis in RAW 264.7 cells. Thus, regular consumption of EGCG in green tea can inhibit the development and progression of osteoclast-related diseases.
饮用绿茶有许多健康益处，包括调节骨代谢和改善骨质疏松症，主要是针对老年和绝经后妇女。这种护骨作用归因于具有生物活性的多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）。虽然 EGCG 可以抑制破骨细胞的生成，但它的潜在分子机制仍有待阐明。核因子（NF）-κB 配体（RANKL）和 RANK 之间的相互作用在破骨细胞的分化和激活中起着关键作用，因此被认为是治疗与破骨细胞相关疾病（如骨质疏松症）的一个靶点。在本研究中，我们发现 EGCG 可以直接与 RANK 和 RANKL 结合，并干扰它们之间的相互作用，从而抑制 RANKL 诱导的 IKKα/β、IκBα、p65、JNK、ERK1/2 和 p38 的磷酸化以及关键下游调节因子，包括激活 T 细胞核因子 c1（NFATc1）、c-Fos、抗酒石酸酸性磷酸酶（TRAP）、c-Src 和组织蛋白酶 K 的磷酸化，最终抑制破骨细胞的生成。综上所述，我们的结果表明，EGCG 可以直接与 RANK 和 RANKL 结合并阻断它们的相互作用，通过抑制 NF-κB 和丝裂原活化蛋白激酶（MAPK）信号通路，负调控 RAW 264.7 细胞中 RANKL 诱导的破骨细胞生成。因此，绿茶中 EGCG 的定期摄入可以抑制与破骨细胞相关的疾病的发展和进展。
