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。预防策略的主要重点一直是饮食中的钙摄入量，然而钙本身的疗效有限。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。在最初的应用中，我的长期目标是为制定旨在通过饮食和补充干预减少骨丢失的策略做出贡献。在最初的R21拨款申请中，目的是评估在实验性骨质疏松症模型中，膳食共轭亚油酸与膳食钙对骨代谢的影响程度。在最初应用的基础上，我们希望通过增加一个新的假设来扩大我们的研究范围，即CLA抑制脂肪生成是CLA对成骨有益作用的一个重要但非关键的贡献因素。这一修订应用的基本原理是，由于间充质干细胞的多潜能性质，研究CLA在平衡脂肪生成和成骨方面的具体作用将有助于理解CLA在最终用于人类健康方面的关键方面。这项修订后的研究将确定共轭亚油酸控制脂肪生成是否对共轭亚油酸对骨健康的影响至关重要。因此，请求修订中的研究与NIH使命中与开发可能有助于减少人类疾病的知识有关的部分相关。新的假设将通过追求一个新的特定目标来检验：(3)确定共轭亚油酸在骨髓间充质干细胞成骨和成脂平衡中的作用。通过使用被击倒的间充质干细胞作为成骨和成脂的靶介质，我们将专注于确定共轭亚油酸在成脂中的作用，这可以直接影响成骨，反之亦然。整个项目的范围是研究共轭亚油酸在改善骨量方面的潜在作用，这可能会导致共轭亚油酸作为膳食补充或食物添加剂应用于预防骨丢失。申请修订的预期贡献是，修订后的应用将有助于全面整合和扩大新的见解，以了解成骨细胞和来自间充质干细胞的脂肪细胞之间的相互关系，以及共轭亚油酸预防骨质疏松症的潜在用途。该项目与公共卫生相关的是，确定任何可以改善骨骼健康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。一种独特的预防策略，通过共轭亚油酸控制骨髓干细胞骨形成和脂肪细胞形成的平衡，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. The main emphasis of prevention strategies 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. My long term goal in the original application is to contribute to the development of strategies designed to reduce bone loss through dietary and supplementary based interventions. The objective in the original R21 grant application is to evaluate the extent to which dietary CLA influence bone metabolism with dietary calcium in an experimental osteoporosis model. Based on the original application, we would like to expand our scope of study by adding a new hypothesis that inhibition of adipogenesis by CLA is a significant but not critical contributing factor for CLA's beneficial effects on osteogenesis. The rationale for this revised application is that investigating the role of CLA specifically on balancing adipogenesis and osteogenesis due to the pluripotential nature of mesenchymal stem cells will help understand the critical aspects of CLA in regard to application for eventual use in human health. This revised study will determine if controlling of adipogenesis by CLA is critical for CLA's impact on bone health. Thus, the research in the requested revision is relevant to that part of NIH's mission that pertains to developing knowledge that will potentially help to reduce human diseases. The new hypotheses will be tested by pursuing a new Specific Aim: (3) Determine the role of CLA in the balance between osteogenesis and adipogenesis in bone marrow mesenchymal stem cells. By using mesenchymal stem cells knocked-down for target mediators of osteogenesis and adipogenesis, we will focus on identifying the role of CLA on adipogenesis that can directly influence osteogenesis or vice versa. The scope of the overall project is to investigate the underlying role of CLA on bone mass improvement, which may lead to the application ofCLA as a dietary supplement or food additive for prevention of bone loss. The anticipated contribution of the requested revision is that the revised application will contribute to comprehensively integrate and expand new insight for understanding the interrelationship between osteoblasts and adipocytes from mesenchymal stem cells as well as the potential use of CLA to prevent osteoporosis. The Public Health relevance of this project is that identifying any dietary components that can improve bone health will have a significant impact on reduction and/or prevention of osteoporosis, which 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 controlling balance of bone formation and fat cell formation from bone marrow stem cell by conjugated linoleic acid can potentially be a very useful tool for preventing the development of osteoporosis, leading to improved quality of life particularly in the elderly.