Osteoporosis is a systemic disease that typically affects older adults and that remains a major threat to global public health owing to its high morbidity and mortality rates. In those with osteoporosis, excess osteoclast (OC)-mediated resorption of bone tissue can lead to an imbalance in normal bone metabolism resulting in the onset of diseases including postmenopausal osteoporosis (PMOP). In the present study, we found that the natural Belamcanda chinensis (L.) DC derivative tectoridin can reduce bone loss in ovariectomized mice. TRAP staining further revealed that tectoridin suppresses OC differentiation in a dose-dependent fashion, and qPCR analyses indicated that this compound also dose-dependently inhibits the RANKL-induced upregulation of OC marker genes including Trap, Ctsk, ATP60, DC-Stamp, c-Fos, and NFATc1 in bone marrow macrophages (BMMs). Tectoridin treatment further suppressed actin ring formation and in vitro bone resorption as determined via F-actin staining and scanning electron microscopy. At the mechanistic level, we found that tectoridin was capable of inhibiting osteoclastogenesis at least in part owing to its ability to interfere with NF-κB pathway activation. In addition, we confirmed that tectoridin was able to protect against in vivo estrogen-deficiency-associated bone loss. Together, these results suggest that tectoridin can inhibit osteoclastogenesis and OC functionality in the context of PMOP at least in part via modulating RANKL-induced NF-κB signaling.

骨质疏松症是一种全身性疾病，通常影响老年人，由于其高发病率和死亡率，仍然对全球公共卫生构成重大威胁。对于骨质疏松症患者，破骨细胞（OC）介导的骨组织吸收过多会导致正常骨代谢失衡，导致绝经后骨质疏松症（PMOP）等疾病的发生。在本研究中，我们发现天然射干DC衍生物鸢尾苷可以减少卵巢切除小鼠的骨质流失。TRAP 染色进一步显示，鸢尾素以剂量依赖性方式抑制 OC 分化，qPCR 分析表明，该化合物还剂量依赖性地抑制 RANKL 诱导的 OC 标记基因的上调，包括 Trap、Ctsk、ATP60、DC-Stamp、c-骨髓巨噬细胞 (BMM) 中的 Fos 和 NFATc1。通过 F-肌动蛋白染色和扫描电子显微镜测定，鸢尾苷治疗进一步抑制肌动蛋白环形成和体外骨吸收。在机制水平上，我们发现鸢尾苷能够抑制破骨细胞生成，至少部分是由于其干扰 NF-κB 通路激活的能力。此外，我们证实鸢尾苷能够预防体内雌激素缺乏相关的骨质流失。总之，这些结果表明，鸢尾素可以至少部分通过调节 RANKL 诱导的 NF-κB 信号传导来抑制 PMOP 背景下的破骨细胞生成和 OC 功能。