Synergistic effects of conjugated linoleic acid and calcium on bone mass

描述(申请人提供)：骨质疏松最重要的干预措施之一是预防骨丢失。关于预防策略，主要强调饮食中的钙摄入量，但钙本身的效果有限。因此，任何能改善钙对骨量影响的成分都能显著改善骨骼健康。共轭亚油酸(CLA)可能是控制骨质疏松症的一个很好的候选者，因为CLA减少了身体脂肪，同时增加了瘦体重和总灰分。然而，已报道的共轭亚油酸对骨量的影响并不一致。我们假设CLA与骨量的不一致是由于饮食中钙含量的差异造成的。这项研究的长期目标是系统地了解饮食中的CLA和饮食中的钙是如何改善骨量的，最终导致它们在预防骨质疏松症中的使用。此R21应用的目的是确定钙的作用和共轭亚油酸增加钙在预防骨质疏松方面的作用。需要检验的两个假设是：(1)共轭亚油酸可改善钙在骨丢失期间对骨量的影响，(2)共轭亚油酸通过促进骨形成同时减少骨髓脂肪来提高骨量。这项拟议研究的基本原理是，这项拟议研究的信息将作为临床试验的基础，可以提供有关使用CLA补充剂和钙预防骨质疏松症的关键信息。因此，拟议的研究与NIH使命中与开发潜在有助于减少人类疾病的知识有关的部分相关。在初步数据的基础上，这些假说将通过追求两个特定的目标来验证：(1)确定CLA在骨丢失期间与钙的相互作用；(2)确定CLA在骨髓间充质干细胞分化中的关键分子机制。在第一个目标下，将在去卵巢小鼠中建立CLA与膳食钙的相互作用以及钙的稳态和骨生理学，以了解CLA与钙的相互作用机制。在第二个目标下，CLA对骨髓脂肪细胞和骨形成的关键分子机制将通过两种不同的方法来鉴定：CLA对骨髓脂肪细胞形成(脂肪生成)的影响和对骨髓间充质干细胞成骨(成骨细胞形成)的影响。这种方法是创新的，因为它利用两种功能成分的相互作用以及骨髓干细胞的分化来理解和应用预防骨质疏松症的知识。该项目与公共卫生相关的是，通过确定任何可以改善钙对骨骼健康的益处的饮食成分，将对减少和/或预防骨质疏松症产生重大影响，从而提高生活质量，特别是老年人的生活质量。 公共卫生相关性：骨质疏松症是一种以骨量减少为特征的疾病，老年人特别容易受到影响，它会影响生活质量，并会因并发症而增加死亡率。通过共轭亚油酸和钙共同治疗的独特预防策略可能是预防骨质疏松症发展的非常有用的工具，从而提高生活质量，特别是在老年人中。

DESCRIPTION (provided by applicant): One of the most important interventions for osteoporosis is prevention of bone loss. Regarding prevention strategies, the main emphasis has been on dietary calcium intake, however calcium by itself has limited efficacy. Thus, any component that can improve calcium's effect on bone mass can improve bone health significantly. Conjugated linoleic acid (CLA) may be a good candidate for controlling osteoporosis based on the observation that CLA reduces body fat while increasing lean mass along with total ash. However, the reported effects of CLA on bone mass have not been consistent. We hypothesized that the inconsistency of CLA with regard to bone mass is due to differences in dietary calcium content. The long term goal of this research is to obtain a systematic understanding of how dietary CLA delivered along with dietary calcium can improve bone mass, eventually leading to their use in preventing osteoporosis. The objective of this R21 application is to identify the effect of calcium and ability of CLA to increase calcium's effect on prevention of osteoporosis. Two hypotheses to be tested are (1) CLA improves calcium's effect on bone mass during a bone loss period, and (2) CLA enhances bone mass by improving bone formation while reducing bone marrow adiposity. The rationale for the proposed research is that information from this proposed research will serve as the basis of clinical trials, which can provide critical information regarding the use of CLA supplementation along with calcium for the prevention of osteoporosis. Thus, the proposed research is relevant to that part of NIH's mission that pertains to developing knowledge that will potentially help to reduce human diseases. Based on preliminary data, these hypotheses will be tested by pursuing two specific aims: (1) Determine the interaction between CLA and calcium during a period of bone loss; and (2) Determine key molecular mechanisms of CLA on bone marrow mesenchymal stem cell differentiation. Under the first aim, the interaction between CLA and dietary calcium in ovariectomized mice will be established along with calcium homeostasis and bone physiology to understand the mechanism of interaction between CLA and calcium. Under the second aim, the key molecular mechanisms of CLA on bone marrow adipocyte and bone formation will be identified by two separate approaches; the effects of CLA on bone marrow adipocyte formation (adipogenesis), and on bone formation (osteoblastogenesis) in bone marrow mesenchymal stem cells. This approach is innovated because it uses two functional ingredients' interaction along with bone marrow stem cell differentiation to understand and apply knowledge for prevention of osteoporosis. The Public Health relevance of this project is that, by identifying any dietary components that can improve calcium's benefit on bone health will have a significant impact on reduction and/or prevention of osteoporosis that can lead to an improved quality of life, particularly in the elderly. PUBLIC HEALTH RELEVANCE: Osteoporosis is a disease characterized by low bone mass, with the elderly particularly susceptible, and it affects the quality of life as well as increasing mortality, due to complications. A unique prevention strategy by co-treatment of conjugated linoleic acid and calcium can potentially be a very useful tool for preventing the development of osteoporosis, leading to improved quality of life particularly in the elderly.