Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL‐induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F‐actin ring formation and tartrate‐resistant acid phosphatase (TRAP) staining in dose‐dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK‐related trigger RANKL by phosphorylation JNK/ERK/p38‐MAPK, IκBα/p65‐NF‐κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K‐AKT‐NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL‐induced RANK‐TRAF6 association and RANKL‐related gene and protein markers such as NFATc1, Cathepsin K, MMP‐9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis.

中文翻译：

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金雀花碱通过阻止 RANKL 诱导的破骨细胞生成来减轻卵巢切除小鼠的骨质流失。

绝经后骨质疏松症（PMOP）是一种雌激素戒断，其特征是老年女性破骨细胞大量产生和激活雌激素。金雀花碱是一种喹啉西啶生物碱，来自豆科（豆科）的种子或其他植物。金雀花碱已显示出多种潜在的药理功能。然而，它对 PMOP 的影响仍然未知。本研究旨在探讨金雀花碱是否能够抑制 RANKL 诱导的破骨细胞生成并预防卵巢切除 (OVX) 小鼠因雌激素缺乏引起的骨质流失。在本研究中，我们研究了金雀花碱对RAW 264.7细胞和骨髓单核细胞（BMM）来源的破骨细胞培养系统的影响，并观察了金雀花碱对卵巢切除（OVX）小鼠模型的影响，以模拟绝经后骨质疏松症。我们发现金雀花碱以剂量依赖的方式抑制 F-肌动蛋白环的形成和抗酒石酸酸性磷酸酶 (TRAP) 染色，并通过凹坑形成测定抑制骨吸收。在分子机制上，金雀花碱通过磷酸化 JNK/ERK/p38-MAPK、IκBα/p65-NF-κB 和 PI3K/AKT 轴来抑制 RANK 相关触发物 RANKL，并显着抑制这些信号通路。然而，AKT 激活剂 SC79 可以挽救 PI3K-AKT-NFATc1 轴的抑制。同时，金雀花碱抑制 RANKL 诱导的 RANK-TRAF6 关联以及 RANKL 相关基因和蛋白标记物，如 NFATc1、组织蛋白酶 K、MMP-9 和 TRAP。我们的研究表明金雀花碱可以通过抑制破骨细胞生成来抑制 OVX 小鼠的骨质流失。所有数据都证明金雀花碱可能是治疗骨质疏松症等破骨细胞相关疾病的有前途的药物。