Studying bone secreted molecules (osteokines) as a novel diabetes diagnostic tool

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To understand the control of the skeleton over energy homeostasis, two levels of regulation are studied: First: A. Intermediary metabolism and bioenergetics of bones in murine models. To achieve this, osteocytes were analyzed for their GLUTs expression and a GLUT knockout murine model was developed to study the effect of intermediary metabolism and its effect on bone health and global energy homeostasis. B. To understand hyperglycemic injury effect on bone cells an experiment was conducted on osteocytes cultured in hyperglycemic conditions. Cell viability was not affected. Major GLUTs expressed by osteocytes were not affected but GLUT4 expression was significantly elevated, which will be pursued further in in vitro experiments to understand its role in osteocytes since it is not expressed at the baseline condition. Several osteokines and receptors were differentially expressed after hyperglycemic injury, including RANKL, BMP7, SOST and NPY1R. Second: Study the effect of energy homeostasis perturbation on osteokines through diseases progression. To achieve this an osteokines profile was developed using LC/MSMS at the baseline which will be compared to profiles at different staged of disease progression.