Synergistic effects of conjugated linoleic acid and calcium on bone mass

描述（由申请人提供）：骨质疏松症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是膳食钙摄入量，但钙本身的功效有限。因此，任何可以改善钙对骨量影响的成分都可以显着改善骨骼健康。共轭亚油酸（CLA）可能是一个很好的候选人，用于控制骨质疏松症的基础上观察，共轭亚油酸减少体脂，同时增加瘦体重沿着总灰分。然而，报道的CLA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膳食钙含量的差异。我在原始申请中的长期目标是促进旨在通过饮食和补充性干预减少骨丢失的策略的发展。最初的R21拨款申请的目的是评估在实验性骨质疏松症模型中，膳食CLA对膳食钙骨代谢的影响程度。基于最初的应用，我们想通过增加一个新的假设来扩大我们的研究范围，即CLA对脂肪形成的抑制是CLA对骨生成有益作用的一个重要但不是关键的贡献因素。该修订申请的基本原理是，由于间充质干细胞的多能性，研究CLA在平衡脂肪生成和骨生成方面的作用将有助于了解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CLA对脂肪生成的控制是否对CLA对骨骼健康的影响至关重要。因此，要求修订的研究与NIH的使命的一部分有关，该使命涉及开发可能有助于减少人类疾病的知识。新的假设将通过追求一个新的具体目标来检验：（3）确定CLA在骨髓间充质干细胞成骨和成脂平衡中的作用。通过使用间充质干细胞敲低成骨和脂肪生成的靶向介质，我们将专注于确定CLA对脂肪生成的作用，可以直接影响成骨，反之亦然。整个项目的范围是研究CLA对骨量改善的潜在作用，这可能导致CLA作为膳食补充剂或食品添加剂用于预防骨质流失。所要求修订的预期贡献是，修订后的申请将有助于全面整合和扩展新的见解，以了解间充质干细胞中成骨细胞和脂肪细胞之间的相互关系以及CLA预防骨质疏松症的潜在用途。该项目的公共卫生相关性在于，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，这可能导致生活质量的改善，特别是老年人。 公共卫生相关性：骨质疏松症是一种以低骨量为特征的疾病，老年人尤其易感，并且由于并发症，它影响生活质量以及增加死亡率。通过共轭亚油酸控制骨髓干细胞的骨形成和脂肪细胞形成的平衡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，从而改善生活质量，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.