Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
J Agric Food Chem. 2021 Nov 10;69(44):13020-13033. doi: 10.1021/acs.jafc.1c04353. Epub 2021 Nov 1.
Phytoestrogens are strongly recommended for treating osteoporosis. Our previous study showed that naringin, a citrus flavonoid, can enhance the bone mass in ovariectomized rats. In this study, we further elucidated the mechanisms of naringin-induced osteoblast maturation and bone healing. Treatment of human osteoblasts with naringin increased cell viability and proliferation. In parallel, exposure to naringin enhanced translocation of estrogen receptor alpha (ERα) to nuclei and its transactivation activity. Sequentially, naringin induced alkaline phosphatase (ALP) mRNA and protein expression and its enzyme activity. Pretreatment with methylpiperidinopyrazole (MPP), a specific inhibitor of ERα, attenuated naringin-induced augmentations in ERα transactivation activity, gene expression, and cell mineralization. The beneficial effects of naringin were also confirmed in mouse MC3T3-E1 cells. Moreover, administration of mice with a bone defect with naringin increased levels of ERα and ALP in damaged sites and simultaneously enhanced the healing rate and bone strength. Nevertheless, treatment with MPP weakened naringin-triggered expression of ERα and ALP and improved bone healing and mass. Therefore, naringin could improve osteoblast mineralization and bone healing via regulating ERα-dependent gene expression. Naringin can be clinically applied for treatment of osteoporosis-related bone diseases.
植物雌激素强烈推荐用于治疗骨质疏松症。我们之前的研究表明，柚皮苷是一种柑橘类黄酮，可增加去卵巢大鼠的骨量。在这项研究中，我们进一步阐明了柚皮苷诱导成骨细胞成熟和骨愈合的机制。柚皮苷处理人成骨细胞可增加细胞活力和增殖。同时，柚皮苷增强了雌激素受体α（ERα）向核内易位及其转录激活活性。随后，柚皮苷诱导碱性磷酸酶（ALP）mRNA 和蛋白表达及其酶活性。用特异性 ERα 抑制剂甲基哌啶吡唑（MPP）预处理可减弱柚皮苷诱导的 ERα 转录激活活性、基因表达和细胞矿化的增强作用。柚皮苷在小鼠 MC3T3-E1 细胞中的有益作用也得到了证实。此外，给予柚皮苷治疗的骨缺损小鼠在受损部位增加了 ERα 和 ALP 的水平，同时提高了愈合率和骨强度。然而，用 MPP 处理可减弱柚皮苷触发的 ERα 和 ALP 的表达，改善骨愈合和骨量。因此，柚皮苷可通过调节 ERα 依赖性基因表达来改善成骨细胞的矿化和骨愈合。柚皮苷可临床应用于治疗与骨质疏松症相关的骨疾病。
