Osteoporosis disturbs the balance of bone metabolism, and excessive bone resorption causes a decrease in bone density, thus increasing the risk of fracture. (−)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea. EGCG has a variety of pharmacological activities. Recently, it was reported that EGCG inhibits osteoclast differentiation, but the details of the mechanism underlying the EGCG-mediated suppression of osteoclastogenesis are unknown. In this study, we investigated the effects of EGCG on several signaling pathways in osteoclastogenesis. EGCG suppressed the expression of the nuclear factor of activated T cells cytoplasmic-1 (NFATc1), the master regulator of osteoclastogenesis. EGCG decreased the expression of cathepsin K, c-Src, and ATP6V0d2 and suppressed bone resorption. We also found that EGCG upregulated heme oxygenase-1 (HO-1) and suppressed the extracellular release of high-mobility group box 1 (HMGB1). In addition, EGCG decreased the expression of the receptor for advanced glycation end products (RAGE), which is the receptor of HMGB1, in osteoclastogenesis. In summary, our study showed that EGCG could inhibit osteoclast differentiation through the downregulation of NFATc1 and the suppression of the HO-1–HMGB1–RAGE pathway. EGCG might have the potential to be a lead compound that suppresses bone resorption in the treatment of osteoporosis.

骨质疏松会扰乱骨代谢的平衡，过度的骨吸收导致骨密度降低，从而增加骨折风险。(-)-Epigallocatechin-3-gallate (EGCG) 是绿茶中含量最丰富的儿茶素。EGCG具有多种药理活性。最近，有报道称 EGCG 抑制破骨细胞分化，但 EGCG 介导的破骨细胞生成抑制机制的细节尚不清楚。在这项研究中，我们研究了 EGCG 对破骨细胞生成中几种信号通路的影响。EGCG 抑制活化 T 细胞细胞质-1 (NFATc1) 的核因子的表达，NFATc1 是破骨细胞生成的主要调节因子。EGCG 降低组织蛋白酶 K、c-Src 和 ATP6V0d2 的表达并抑制骨吸收。我们还发现 EGCG 上调血红素加氧酶-1 (HO-1) 并抑制高迁移率族框 1 (HMGB1) 的细胞外释放。此外，EGCG 降低了破骨细胞生成中 HMGB1 受体晚期糖基化终产物 (RAGE) 受体的表达。总之，我们的研究表明，EGCG 可以通过下调 NFATc1 和抑制 HO-1–HMGB1–RAGE 通路来抑制破骨细胞分化。EGCG 有可能成为一种先导化合物，在骨质疏松症的治疗中抑制骨吸收。我们的研究表明，EGCG 可以通过下调 NFATc1 和抑制 HO-1-HMGB1-RAGE 通路来抑制破骨细胞分化。EGCG 有可能成为一种先导化合物，在骨质疏松症的治疗中抑制骨吸收。我们的研究表明，EGCG 可以通过下调 NFATc1 和抑制 HO-1-HMGB1-RAGE 通路来抑制破骨细胞分化。EGCG 有可能成为一种先导化合物，在骨质疏松症的治疗中抑制骨吸收。