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

研究骨分泌分子（骨因子）作为新型糖尿病诊断工具

• 批准号: 22K20647
• 负责人: MARAHLEH ASEEL・MAHMOUD・SULEIMAN
• 金额: $ 1.83万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-08-31 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K20647/
• 关键词: Skeleton; Osteokines; Obesity; Diabetes; Proteomics; Animal models; Skeletal regulation; Osteocyte; Energy metabolism; Skeletal Endocrinology

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.

为了了解骨骼对能量动态平衡的控制，研究了两个水平的调节：第一，小鼠模型中骨骼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，并建立了Glut基因敲除小鼠模型，以研究中间代谢的影响及其对骨健康和全球能量平衡的影响。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。细胞活力未受影响。骨细胞表达的主要谷氨酸没有受到影响，但GLUT4的表达显著增加，由于GLUT4在基线条件下不表达，这将在体外实验中进一步研究其在骨细胞中的作用。在高血糖损伤后，RANKL、BMP7、SOST和NPY1R等多种骨因子及其受体均有不同程度的表达。第二：研究能量稳态扰动通过疾病进展对骨因子的影响。为了实现这一点，使用LC/MSMS在基线上开发了骨因子图谱，并将其与疾病进展不同阶段的图谱进行比较。