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Abstract：
BACKGROUND: Postmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast formation and function. Targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Cirsilineol, an active constituent of Vestita Wall, has shown numerous biological activities and has been used to treat many metabolic diseases. However, whether cirsilineol inhibits osteoclast activity and prevents postmenopausal osteoporosis still remain unknown.
METHODS: Primary bone marrow macrophages (BMMs) and RAW264.7 cells were used. Osteoclast activity was measured by TRAP staining, F-actin staining, and bone resorption assay after BMMs were treated with cirsilineol at concentrations of 0, 1, 2.5 and 5 µM. RT-PCR and western blotting were performed to evaluate the expression of osteoclast-related genes. In addition, female C57BL/6 mice underwent OVX surgery and were treated with cirsilineol (20 mg/kg) to demonstrate the effect of cirsilineol on osteoporosis.
RESULTS: Cirsilineol significantly inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation in a concentration- and time-dependent manner, respectively. Additionally, cirsilineol inhibited F-actin ring formation, thus reducing the activation of bone resorption ability. Cirsilineol suppressed the expression of osteoclast-related genes and proteins via blocking nuclear factor (NF)-κb, ERK, and p38 signaling cascades. More importantly, cirsilineol treatment in mice with osteoporosis alleviated osteoclasts hyperactivation and bone mass loss caused by estrogen depletion.
CONCLUSIONS: In this study, the protective effect of cirsilineol on osteoporosis has been investigated for the first time. In conclusion, our findings prove the inhibitory effect of cirsilineol on osteoclast activity via NF-κb/ERK/p38 signaling pathways and strongapplication of cirsilineol can be proposed as a potential therapeutic strategy.
METHODS: Primary bone marrow macrophages (BMMs) and RAW264.7 cells were used. Osteoclast activity was measured by TRAP staining, F-actin staining, and bone resorption assay after BMMs were treated with cirsilineol at concentrations of 0, 1, 2.5 and 5 µM. RT-PCR and western blotting were performed to evaluate the expression of osteoclast-related genes. In addition, female C57BL/6 mice underwent OVX surgery and were treated with cirsilineol (20 mg/kg) to demonstrate the effect of cirsilineol on osteoporosis.
RESULTS: Cirsilineol significantly inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation in a concentration- and time-dependent manner, respectively. Additionally, cirsilineol inhibited F-actin ring formation, thus reducing the activation of bone resorption ability. Cirsilineol suppressed the expression of osteoclast-related genes and proteins via blocking nuclear factor (NF)-κb, ERK, and p38 signaling cascades. More importantly, cirsilineol treatment in mice with osteoporosis alleviated osteoclasts hyperactivation and bone mass loss caused by estrogen depletion.
CONCLUSIONS: In this study, the protective effect of cirsilineol on osteoporosis has been investigated for the first time. In conclusion, our findings prove the inhibitory effect of cirsilineol on osteoclast activity via NF-κb/ERK/p38 signaling pathways and strongapplication of cirsilineol can be proposed as a potential therapeutic strategy.
摘要：
背景：绝经后骨质疏松症是一种由破骨细胞形成和功能过度引起的慢性代谢性骨病。靶向破骨细胞分化和活性可以调节骨吸收和减轻骨质疏松。Cirsilineol,VestitaWall的活跃组成部分，已显示出许多生物活性，并已用于治疗许多代谢疾病。然而,cirsilineol是否抑制破骨细胞活性和预防绝经后骨质疏松症仍然未知。
方法:使用原代骨髓巨噬细胞(BMM)和RAW264.7细胞。通过TRAP染色测量破骨细胞活性,F-肌动蛋白染色,用浓度为0、1、2.5和5µM的cirsilineol处理BMM后的骨吸收测定。采用RT-PCR和蛋白质印迹法检测破骨细胞相关基因的表达。此外,雌性C57BL/6小鼠接受了OVX手术，并用cirsilineol（20mg/kg）治疗，以证明cirsilineol对骨质疏松症的影响。
结果：Cirsilineol以浓度和时间依赖性方式显着抑制核因子κB配体（RANKL）受体激活剂诱导的破骨细胞分化，分别。此外,cirsilineol抑制F-肌动蛋白环的形成，从而降低骨吸收能力的激活。Cirsilineol通过阻断核因子（NF）-κb抑制破骨细胞相关基因和蛋白质的表达，ERK,和p38信号级联。更重要的是,患有骨质疏松症的小鼠中的cirsilineol治疗减轻了破骨细胞的过度活化和由雌激素消耗引起的骨量损失。
结论：在这项研究中，首次研究了cirsilineol对骨质疏松症的保护作用。总之,我们的研究结果证明了cirsilineol通过NF-κb/ERK/p38信号通路对破骨细胞活性的抑制作用,cirsilineol的有效应用可作为一种潜在的治疗策略.
方法:使用原代骨髓巨噬细胞(BMM)和RAW264.7细胞。通过TRAP染色测量破骨细胞活性,F-肌动蛋白染色,用浓度为0、1、2.5和5µM的cirsilineol处理BMM后的骨吸收测定。采用RT-PCR和蛋白质印迹法检测破骨细胞相关基因的表达。此外,雌性C57BL/6小鼠接受了OVX手术，并用cirsilineol（20mg/kg）治疗，以证明cirsilineol对骨质疏松症的影响。
结果：Cirsilineol以浓度和时间依赖性方式显着抑制核因子κB配体（RANKL）受体激活剂诱导的破骨细胞分化，分别。此外,cirsilineol抑制F-肌动蛋白环的形成，从而降低骨吸收能力的激活。Cirsilineol通过阻断核因子（NF）-κb抑制破骨细胞相关基因和蛋白质的表达，ERK,和p38信号级联。更重要的是,患有骨质疏松症的小鼠中的cirsilineol治疗减轻了破骨细胞的过度活化和由雌激素消耗引起的骨量损失。
结论：在这项研究中，首次研究了cirsilineol对骨质疏松症的保护作用。总之,我们的研究结果证明了cirsilineol通过NF-κb/ERK/p38信号通路对破骨细胞活性的抑制作用,cirsilineol的有效应用可作为一种潜在的治疗策略.
