Abstract
Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. in vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.
Highlights
The availability of large in vitro cell and tissue omic datasets and bioinformatic tools have equipped researchers to understand molecular processes that cause disease, and identify and develop new therapeutics [1]
Positron emission tomography (PET) imaging allows for the non-invasive in vivo investigation of signalling pathways owing to the radiotracer principle and total-body dynamic PET lends itself to deciphering complex biological processes and interactions [2,3,4,5,6], such as those found associated with the skeletal system
18F-FDG PET imaging has been extensively used for quantification of glucose metabolism in vivo
Summary
The availability of large in vitro cell and tissue omic datasets and bioinformatic tools have equipped researchers to understand molecular processes that cause disease, and identify and develop new therapeutics [1]. Novel systems approaches are needed to understand complex in vivo physiological and pathological interactions at multi-tissue level. Positron emission tomography (PET) imaging allows for the non-invasive in vivo investigation of signalling pathways owing to the radiotracer principle and total-body dynamic PET lends itself to deciphering complex biological processes and interactions [2,3,4,5,6], such as those found associated with the skeletal system. We present an integrative approach to understand complex tissue interactions in vivo using total-body PET network analysis that is directly applicable to emerging clinical total-body dynamic imaging. We initially focused on the skeletal system as it provides an ideal model for analysing complex interactions. The skeleton serves multiple functions in vivo such as organ protection, allowing for
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