Michigan Integrative Musculoskeletal Health Core Center – Core B Project Summary Structure and composition across physiological length-scales are key intermediate traits that link gene expression with functional outcomes. Genetic and/or environmental perturbations affecting gene expression often lead to measureable changes in these intermediate traits that have mechanical and other functional consequences. Accurately quantifying structure and composition at different length scales is therefore essential to advancing our understanding of the molecular and mechanical mechanisms underlying musculoskeletal health and disease; to develop and evaluate treatment strategies; and to ultimately translate these strategies to the clinic. However, this research requires use of advanced and costly instruments and supporting expertise in cell biology, chemistry, engineering, and biomedical imaging. The Structure, Composition and Histology Core (Core B) will provide access to the instruments and expertise that will enable Center investigators to quantify these intermediate traits and to accelerate their research programs. Core B will include ex-vivo micro-Computed Tomography (µCT) and nano-Computed Tomography (nano-CT), Raman spectroscopy, and histology as its major components. These technologies were chosen for their applicability to all musculoskeletal tissues and based on usage data over the previous 4 years and a needs-assessment survey of core users. Investigators at the University of Michigan pioneered the use of µCT and Raman spectroscopy to investigate musculoskeletal tissues and are leaders in applying these technologies to solve musculoskeletal problems. Histology continues to be the gateway approach to understanding changes in tissue morphology and, when combined with CT and Raman spectroscopy, histology can link tissue morphology to composition and functional outcomes. The goals of this Core are to leverage the expertise of the core leadership to support the research programs of Center investigators in performing structural, compositional and histological analyses of all musculoskeletal tissues, both intellectually and financially; to expand opportunities for our research community; and to bring new investigators into the musculoskeletal community. To accomplish our goals and to continue creating a robust and sustainable impact to the musculoskeletal community in the P30 renewal application, we propose the following Specific Aims: Aim 1: To provide expertise and guidance on the best use of technologies and experimental design to allow investigators to conduct specialized assays for quantifying structure and composition across length scales. Aim 2: To provide expert use, standardization, and training in state-of-the-art technologies to quantify structure and composition across physiological length scales. Aim 3: To provide expertise and scientific guidance on data analysis, interpretation of results and recommendations for future studies. Aim 4: To ex...