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质流失。关于预防策略，主要强调的是饮食中的钙摄入，然而钙本身的功效有限。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良好候选者，因为它可以减少体脂，同时增加瘦质量和总灰分。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饮食中钙含量的差异。本研究的长期目标是系统地了解膳食CLA与膳食钙如何改善骨量，并最终用于预防骨质疏松症。本R21应用的目的是确定钙的作用和CLA增加钙预防骨质疏松的作用的能力。需要验证的两个假设是：(1)CLA在骨质流失期间改善钙对骨量的影响，(2)CLA通过促进骨形成同时减少骨髓脂肪来增强骨量。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，临床试验可以提供有关使用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的使命有关，即开发可能有助于减少人类疾病的知识。基于初步数据，这些假设将通过追求两个具体目标来验证：(1)确定骨质流失期间CLA和钙之间的相互作用；(2)确定CLA对骨髓间充质干细胞分化的关键分子机制。本研究旨在建立去卵巢小鼠CLA与饲料钙的相互作用，并结合钙稳态和骨生理学研究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确定；CLA对骨髓脂肪细胞形成（adipogenesis）和骨髓间充质干细胞成骨（osteoblastgenesis）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分化来理解和应用预防骨质疏松症的知识。该项目的公共卫生相关性在于，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。

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.