AIMS Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed) is a pentacyclic triterpenoid saponin extracted from various natural medicinal plants and exhibits numerous biological activities and may offer benefits against bone-related conditions. We evaluated the effects of Hed on osteoclast formation and bone resorption in vitro and the in vivo therapeutic benefits in the mouse model of ovariectomy (OVX)-induced bone loss. MAIN METHODS In vitro, osteoclast formation were determined by TRAcp staining; bone resorption were examined using Hydroxyapatite resorption assay and Podosomal actin belt formation assay; Related molecular mechanisms were determined by western blot assay. Construction of OVX mice by bilateral oophorectomy to simulate bone loss in vivo. KEY FINDINGS In vitro cellular assays showed that Hed inhibited RANKL-induced osteoclast formation and osteoclast bone (hydroxyapatite) resorption as well as marker gene expression from BMM culture. Mechanistically, Hed attenuated RANKL-induced intracellular reactive oxygen species (ROS) production, and MAPK signaling pathway (ERK and p38) activation which curbed the downstream induction of c-Fos and NFATc1. Consistent with the in vitro findings, Hed administration effectively protected OVX mice from bone loss by reducing osteoclast number and activity on bone surface. SIGNIFICANCE Our data provided promising evidence for the potential use of Hederagenin in the treatment of osteoclast-mediated osteolytic bone diseases such as postmenopausal osteoporosis.

中文翻译：

---

角质生成素通过抑制RANKL诱导的破骨细胞生成和骨吸收来保护小鼠免受卵巢切除术诱导的骨丢失。

AIMS绝经后骨质疏松症和其他溶骨性疾病通常是由破骨细胞增多和/或破骨细胞骨吸收增加引起，导致骨量过多丢失。角质生成素（Hederagenin，Hed）是一种从各种天然药用植物中提取的五环三萜皂苷，具有多种生物学活性，可能对骨骼相关疾病有益。我们在卵巢切除术（OVX）诱导的骨丢失小鼠模型中评估了Hed在体外对破骨细胞形成和骨吸收的影响以及体内治疗的益处。主要方法在体外，破骨细胞形成是通过TRAcp染色确定的。用羟磷灰石吸收试验和足小肌动蛋白带形成试验检查骨吸收。通过Western印迹分析确定相关的分子机制。通过双侧卵巢切除术构建OVX小鼠以模拟体内骨丢失。主要发现体外细胞分析表明，Hed抑制RANKL诱导的破骨细胞形成和破骨细胞（羟基磷灰石）吸收以及BMM培养物中的标记基因表达。从机理上讲，Hed减弱了RANKL诱导的细胞内活性氧（ROS）的产生，并减弱了MAPK信号通路（ERK和p38）的激活，从而抑制了c-Fos和NFATc1的下游诱导。与体外研究结果一致，Hed给药通过减少破骨细胞数量和骨表面活性来有效保护OVX小鼠免受骨质流失。意义我们的数据提供了有前景的证据，证明了赫德拉金宁在治疗破骨细胞介导的溶骨性骨病（如绝经后骨质疏松症）中的潜在用途。