Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
J Agric Food Chem. 2020 Sep 30;68(39):10639-10650. doi: 10.1021/acs.jafc.0c02830. Epub 2020 Sep 8.
Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.
骨质疏松症相关骨折可能导致更高的发病率和死亡率。我们之前的研究表明，植物雌激素金雀异黄素对雌激素受体 α（ERα）基因表达的诱导和成骨细胞矿化的刺激作用。在这项研究中，我们使用大鼠颅骨成骨细胞和动物骨缺损模型来研究金雀异黄素对骨愈合的影响。金雀异黄素处理可使大鼠成骨细胞碱性磷酸酶（ALP）活性呈时间依赖性增加。金雀异黄素处理后细胞浆和核 ERα 水平显著增加。随后，金雀异黄素上调了大鼠成骨细胞中 ALP mRNA 和蛋白的水平。此外，金雀异黄素诱导了其他与成骨相关的骨钙素和 Runx2 mRNA 和蛋白的表达。使用 RNA 干扰敲低 ERα 可同时抑制金雀异黄素诱导的 Runx2、骨钙素和 ALP mRNA 表达。引人注目的是，给患有骨缺损的 ICR 小鼠施用金雀异黄素可显著增加骨痂宽度、软骨细胞增殖和 ALP 合成。微计算机断层扫描结果显示，金雀异黄素给药可增加小梁骨数量，改善骨厚度和体积。这项研究表明，金雀异黄素可以通过触发 ERα 介导的成骨相关基因表达和随后的成骨细胞成熟来改善骨愈合。
