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

为了了解骨骼对能量平衡的控制，研究了两个层次的调节：第一：A。小鼠模型中骨的中间代谢和生物能量学。为了实现这一点，分析了骨细胞的GLUT表达，并开发了GLUT敲除小鼠模型，以研究中间代谢的作用及其对骨健康和整体能量稳态的作用。B。为了了解高血糖对骨细胞的损伤作用，对高血糖条件下培养的骨细胞进行了实验。细胞活力不受影响。骨细胞表达的主要GLUT不受影响，但GLUT 4表达显著升高，由于其在基线条件下不表达，因此将在体外实验中进一步研究以了解其在骨细胞中的作用。在高血糖损伤后，几种骨因子和受体表达差异，包括RANKL，BMP 7，SOST和NPY 1 R。第二，通过疾病进展研究能量稳态紊乱对骨因子的影响。为了实现这一点，在基线时使用LC/MSMS开发了骨因子谱，将其与疾病进展的不同阶段的谱进行比较。

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.