A PEDIGREED BABOON MODEL FOR THE GENETICS OF CORTICAL BONE MATERIAL PROPERTIES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 直到最近，大多数抗骨折性的研究都集中在骨量上。 然而，流行病学研究现在表明，骨折风险的一个显着比例是独立的骨量。除了年龄和性别的影响外，骨强度的替代指标（例如骨矿物质含量和密度）始终显示出显着的遗传效应。虽然已经在啮齿动物中进行了骨骼材料特性的遗传研究，但还没有在人类或其他灵长类动物中进行类似的研究。其他物种和灵长类动物之间的骨折特性的实质性差异强调了需要一个遗传特征良好的非人灵长类动物模型，用于骨材料特性的遗传学研究。我们建议研究基因对皮质骨材料特性的贡献，直接测量骨质量，这是骨结构完整性的重要方面。本研究的最终目的是建立狒狒作为人类骨材料特性遗传研究的模型。利用从100只纯种成年狒狒右股骨收集的数据，该项目的具体目标是：1）确定皮质骨组织性质，包括弹性模量、屈服和极限强度、屈服后行为、断裂韧性，和矿化（灰分分数和microCT测定的骨矿物质密度），并确定皮质骨密度和矿化程度（灰分分数）与皮质骨材料性质相关; 2）表征狒狒中皮质骨材料性质的正常变化，包括年龄和性别效应;和3）检测和量化由于基因的加性效应引起的这些性质的变化的比例。我们将评估基因对本项目中确定的皮质骨性质与其他研究确定的松质骨材料性质的影响的相对大小。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Until recently, a majority of studies of bone fracture resistance focused on bone mass. However, epidemiological studies now suggest that a significant proportion of fracture risk is independent of bone mass. In addition to the effects of age and sex, proxy measures of bone strength (e.g. bone mineral content and density) consistently show significant genetic effects. While genetic studies of bone material properties have been conducted in rodents, similar studies have not been done in humans or other primates. Substantial differences in fracture properties between other species and primates underscore the need for a genetically well-characterized non-human primate model for studies of the genetics of bone material properties. We propose to investigate the contribution of genes to cortical bone material properties, direct measures of bone quality that are essential aspects of a bone's structural integrity. The ultimate objective of the proposed study is to establish the baboon as a model for the genetic study of human bone material properties. Using data collected from the right femur of 100 pedigreed adult baboons, the specific aims of this project are to: 1) determine cortical bone tissue properties including elastic modulus, yield and ultimate strength, post-yield behavior, fracture toughness, and mineralization (ash fraction and microCT-determined bone mineral density) and determine the degree to which cortical bone density and mineralization (ash fraction) are correlated to cortical bone material properties; 2) characterize normal variation, including age and sex effects, on cortical bone material properties in the baboon; and 3) detect and quantify the proportion of variation in these properties that is due to the additive effects of genes. We will assess the relative magnitude of the effect of genes on cortical bone properties as determined in this project vs. trabecular bone material properties determined from other research.