Food Bioactives and Bone Metabolism

这项研究计划的重点是纠正或减弱骨转换的失调，发生在衰老过程中使用食品药物协同作用。我们假设食物生物活性物质（茶中的黄酮类化合物）与药物干预（低剂量雌激素）相结合可以提供一种安全有效的策略来使骨转换正常化。习惯性饮茶与女性较高的骨密度（BMD）密切相关，而男性的数据较少。茶中的黄酮可能是介导这些益处的活性成分，并通过多种机制，包括雌激素样作用，抗氧化活性和抗炎活性。我们有很有希望的数据表明，木犀草素和orientin，类黄酮独特的rooibos茶-并提供绿色，黑色和rooibos茶-刺激成骨细胞的活动。这些数据为研究茶及其促进年龄介导性类固醇下降的啮齿动物模型（卵巢切除（Ovx）和卵巢切除（Orch）大鼠）中骨转换调节的能力的拟议研究提供了强有力的依据。** 总体目标是阐明食物生物活性物质（即来自绿色、红茶和路易波士茶的类黄酮）单独或与低剂量雌激素组合调节骨细胞代谢的机制。总的假设是，与单独的类黄酮或低剂量雌激素相比，提供来自茶的类黄酮与低剂量雌激素将刺激成骨细胞活性并在更大程度上下调骨细胞活性。** 科学方法涉及使用成熟的Ovx或Orch大鼠模型来模拟正常衰老期间发生的骨细胞代谢变化，并导致氧化应激水平升高和低度炎症，从而解除骨细胞代谢（形成，吸收）。对Ovx和Orch大鼠骨组织的分析可以通过确定成骨细胞活性的五个主要方面的关键介质的水平和活性来确定单独的饮食策略或低剂量雌激素调节氧化应激和低度炎症的机制。这些方面包括i.细胞数量; ii.基质生产; iii.生长因子表达和反应性; iv.调节骨吸收的因子;和v.受体表达和信号转导。为了理解这些机制如何与全骨相关，在整个研究期间将在同一大鼠中测量骨的体内功能测量，例如BMD、骨强度和三维骨结构。还将测量脂肪和瘦体重，因为它们可能会通过干预改变并调节骨骼结果。*预期意义：这项研究将阐明茶中的黄酮类化合物可能有利地调节骨细胞代谢的机制，以及增加或减少雌激素治疗减轻骨代谢失调的能力。

This research program has focused on correcting or attenuating the dysregulation of bone turnover that occurs during aging using food-drug synergy. We hypothesize that food bioactives (flavonoids from tea) in combination with drug interventions (low dose estrogen) can provide a safe and effective strategy to normalize bone turnover. Habitual consumption of tea is strongly associated with higher bone mineral density (BMD) in women with less data in men. Flavonoids in tea may be the active component mediating these benefits and through multiple mechanisms, including estrogen-like effects, antioxidant activity and anti-inflammatory activity. We have promising data that luteolin and orientin, flavonoids unique to rooibos tea - and that providing green, black and rooibos tea - stimulate osteoblast activity. These data provide a strong rationale for the proposed studies investigating tea and its ability to promote regulation of bone turnover in rodent models of age-mediated declines in sex steroids (ovariectomized (Ovx) and orchidectomized (Orch) rats). ******The overall objective is to elucidate the mechanisms by which food bioactives (i.e. flavonoids from green, black and rooibos tea) alone or in combination with low dose estrogen modulate bone cell metabolism. The overall hypothesis is that providing flavonoids from tea with low dose estrogen will stimulate osteoblast activity and downregulate osteoclastic activity to a greater extent than flavonoids or low dose estrogen alone. ******The scientific approach involves using the well-established Ovx or Orch rat model to simulate changes in bone cell metabolism that occur during normal aging and result in elevated levels of oxidative stress and low-grade inflammation that uncouples bone cell metabolism (formation,resorption). Analysis of bone tissue from Ovx and Orch rats can determine mechanisms by which dietary strategies alone, or with low dose estrogen, modulate oxidant stress and low-grade inflammation by determining the levels and activity of key mediators of five main aspects of osteoblast activity. These aspects include regulation of i. cell numbers; ii. matrix production; iii. growth factor expression and responsiveness; iv. factors that modulate bone resorption; and v. receptor expression and signal transduction. To understand how these mechanisms relate to whole bone, in vivo functional measures of bone such as BMD, bone strength and 3-dimensional bone structure will be measured in the same rat throughout the study. Fat and lean mass will also be measured as they may be altered by an intervention and modulate bone outcomes.******Expected significance: This research will elucidate the mechanisms by which flavonoids from tea may favourably regulate bone cell metabolism, and also, augment or lessen the ability of estrogen therapy to attenuate dysregulation of bone metabolism.**