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首页> 外文期刊>The Journal of Nutritional Biochemistry >Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats: evidence for estrogen receptor beta-mediated osteogenic action of medicarpin.
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Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats: evidence for estrogen receptor beta-mediated osteogenic action of medicarpin.

机译：Medicarpin是一种豆科植物抗植物生长素，可刺激大鼠成骨细胞分化并促进峰值骨量形成：雌激素受体β介导的medicarpin成骨作用的证据。

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摘要

Dietary isoflavones including genistein and daidzein have been shown to have favorable bone conserving effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of medicarpin (Med); a phytoalexin that is structurally related to isoflavones and is found in dietary legumes. Med stimulated osteoblast differentiation and mineralization at as low as 10--10 M. Studies with signal transduction inhibitors demonstrated involvement of a p38 mitogen activated protein kinase-ER-bone morphogenic protein-2 pathway in mediating Med action in osteoblasts. Co-activator interaction studies demonstrated that Med acted as an estrogen receptor (ER) agonist; however, in contrast to 17 beta-estradiol, Med had no uterine estrogenicity and blocked proliferation of MCF-7 cells. Med increased protein levels of ER beta in osteoblasts. Selective knockdown of ER alpha and ER beta in osteoblasts established that osteogenic action of Med is ER beta-dependent. Female Sprague-Dawley (weaning) rats were administered Med at 1.0- and 10.0 mg.kg--1 doses by gavage for 30 days along with vehicle control. Med treatment resulted in increased formation of osteoporgenitor cells in the bone marrow and osteoid formation (mineralization surface, mineral apposition/bone formation rates) compared with vehicle group. In addition, Med increased cortical thickness and bone biomechanical strength. In pharmacokinetic studies, Med exhibited oral bioavailability of 22.34% and did not produce equol. Together, our results demonstrate Med stimulates osteoblast differentiation likely via ER beta, promotes achievement of peak bone mass, and is devoid of uterine estrogenicity. In addition, given its excellent oral bioavailability, Med can be potential osteogenic agent
机译：食用异黄酮（包括染料木黄酮和黄豆苷元）已被证明在实验动物和人类的雌激素缺乏期间具有良好的骨保护作用。我们评估了麦地卡宾（Med）的成骨作用;在结构上与异黄酮相关的植物抗毒素，在饮食类豆类中发现。 Med刺激低至10 -10 M的成骨细胞分化和矿化。信号转导抑制剂的研究表明，p38丝裂原活化蛋白激酶-ER-骨形态发生蛋白2通路参与介导Med作用在成骨细胞中。共激活剂相互作用研究表明，Med充当雌激素受体（ER）激动剂。但是，与17种β-雌二醇相反，Med没有子宫雌激素性，并阻断了MCF-7细胞的增殖。 Med增加了成骨细胞中ERβ的蛋白质水平。选择性敲低成骨细胞中的ERα和ERβ证实了Med的成骨作用是ERβ依赖性的。雌性Sprague-Dawley（断奶）大鼠通过管饲法分别以1.0和10.0 mg.kg -1 剂量的Med给药，并与媒介物对照一起服用30天。与媒介物组相比，Med治疗导致骨髓中骨成因细胞的形成增加，类骨质形成（矿化表面，矿物质沉积/骨形成速率）增加。此外，Med增加了皮质的厚度和骨骼的生物力学强度。在药代动力学研究中，Med表现出22.34％的口服生物利用度，并且未产生雌马酚。总之，我们的结果表明Med可能通过ER beta刺激成骨细胞分化，促进达到峰值骨量，并且没有子宫雌激素。此外，鉴于其出色的口服生物利用度，Med可能是潜在的成骨剂

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