Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Eur J Pharmacol. 2024 Aug 15;977:176666. doi: 10.1016/j.ejphar.2024.176666. Epub 2024 May 24.
Osteoporosis is a highly prevalent bone metabolic disease in menopause due to estrogen deficiency. Hyperoside is a main compound in Semen cuscutae. Our team previously reported that Semen cuscutae has anti osteoporosis effect on ovariectomized mice by inhibiting bone resorption of osteoclasts. However, it is still unclear whether hyperoside affects osteoclast differentiation and bone resorption, and whether its anti-osteoporosis effect is related to an estrogen-like effect. This study investigates the potential mechanism of hyperoside's anti-osteoporotic effect by examining its impact on osteoclast differentiation and its relationship with the estrogen receptor. DXA, Micro-CT, TRAP staining, HE, and ELISA were used to assess the impact of hyperoside on OVX-induced osteoporosis. The effect of hyperoside on octeoclast differentiation was evaluated using TRAP activity assay, TRAP staining, F-actin staining. The activation of the estrogen receptor by hyperoside and its relationship with osteoclast differentiation were detected using dual-luciferase reporter assay and estrogen receptor antagonists. Our findings revealed that hyperoside (20-80 mg/kg) protect against OVX-induced osteoporosis, including increasing BMD and BMC and improving bone microstructure. Hyperoside inhibited osteoclast differentiation in a concentration dependent manner, whereas estrogen receptor α antagonists reversed its inhibitory effect osteoclast differentiation. Western blot results suggested that hyperoside inhibited TRAP, RANKL, c-Fos and ITG β3 protein expression in osteoclast or femoral bone marrow of ovariectomized mice. Our findings suggest that hyperoside inhibits osteoclast differentiation and protects OVX-induced osteoporosis through the ERα/ITGβ3 signaling pathway.
骨质疏松症是绝经后由于雌激素缺乏导致的一种高发骨代谢疾病。桃叶珊瑚苷是菟丝子中的主要化合物。我们的团队之前报道过，菟丝子通过抑制破骨细胞的骨吸收对去卵巢小鼠具有抗骨质疏松作用。然而，桃叶珊瑚苷是否影响破骨细胞分化和骨吸收，以及其抗骨质疏松作用是否与雌激素样作用有关，目前尚不清楚。本研究通过研究桃叶珊瑚苷对破骨细胞分化的影响及其与雌激素受体的关系，探讨其抗骨质疏松作用的潜在机制。DXA、Micro-CT、TRAP 染色、HE 和 ELISA 用于评估桃叶珊瑚苷对 OVX 诱导的骨质疏松的影响。使用 TRAP 活性测定、TRAP 染色、F-肌动蛋白染色评估桃叶珊瑚苷对破骨细胞分化的影响。使用双荧光素酶报告基因检测和雌激素受体拮抗剂检测桃叶珊瑚苷对雌激素受体的激活及其与破骨细胞分化的关系。我们的研究结果表明，桃叶珊瑚苷（20-80mg/kg）可预防 OVX 诱导的骨质疏松症，包括增加 BMD 和 BMC 以及改善骨微结构。桃叶珊瑚苷呈浓度依赖性抑制破骨细胞分化，而雌激素受体 α 拮抗剂则逆转了其对破骨细胞分化的抑制作用。Western blot 结果表明，桃叶珊瑚苷抑制破骨细胞或去卵巢小鼠股骨中 TRAP、RANKL、c-Fos 和 ITGβ3 蛋白的表达。我们的研究结果表明，桃叶珊瑚苷通过 ERα/ITGβ3 信号通路抑制破骨细胞分化并保护 OVX 诱导的骨质疏松症。
