Osteoporosis has been attributed to low bone mass arising from cellular communications between bone formation and bone resorption. Osteoclastogenesis is induced by M-CSF and RANKL in hematopoietic lineage cells. Once RANK/RANKL complex is formed, TRAF6 is recruited and triggers the activation of NF-κB pathway and the expression of osteoclast-related genes including NFATc1. Neotuberostemonine (NTS) is an active compound isolated from Stemona tuberosa Lour. Pharmacologically, NTS has been known to possess antitussive, anti-fibrotic and anti-inflammatory activities through regulation of macrophage. However, the influence of NTS to osteoclastogenesis has not been reported. The purpose of this study is to investigate whether NTS can modulate the osteoclastogenesis induced by RANKL or cancer cells. We found that NTS inhibits RANKL- or cancer cell-mediated osteoclastogenesis via blockade of TRAF6 and NF-κB activation. NTS also impairs the formation of F-actin ring structure, an important feature of osteoclast differentiation and function. These results indicate that NTS can be a preventive and therapeutic candidate for bone-related disease and that NTS provides insights underlying molecular mechanisms that influence osteoclastogenesis.

骨质疏松症归因于骨形成和骨吸收之间的细胞通讯引起的骨量低。造血细胞系中的M-CSF和RANKL诱导破骨细胞生成。一旦形成RANK / RANKL复合物，便会募集TRAF6，并触发NF-κB途径的激活和破骨细胞相关基因（包括NFATc1）的表达。Neotuberostemonine（NTS）是一种分离自Stenona tuberosa Lour的活性化合物。在药理上，已知NTS通过调节巨噬细胞具有镇咳，抗纤维化和消炎的活性。然而，尚未报道NTS对破骨细胞形成的影响。这项研究的目的是调查NTS是否可以调节RANKL或癌细胞诱导的破骨细胞生成。我们发现NTS通过阻断TRAF6和NF-κB激活来抑制RANKL或癌细胞介导的破骨细胞生成。NTS还损害F-肌动蛋白环结构的形成，这是破骨细胞分化和功能的重要特征。这些结果表明NTS可以作为骨相关疾病的预防和治疗候选药物，并且NTS提供了影响破骨细胞生成的分子机制的深刻见解。