2022 Fiscal Year Research-status Report
Studying bone secreted molecules (osteokines) as a novel diabetes diagnostic tool
| Project/Area Number |
22K20647
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | Skeleton / Osteokines / Obesity / Diabetes / Proteomics / Animal models |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Bone cells (osteocytes) transcriptomic landscape after acute hyperglycemic injury was analyzed. This analysis will be used for further downstream knockout-in experiments of several differentially expressed genes. Additionally, a proteomic profile of osteokines at baseline healthy stage was developed, this profile will be compared to profiles at multiple stages of metabolic disease progression which an
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| Strategy for Future Research Activity |
This work will be continued by analyzing the impact of the knockout on skeletal maturation and osteogenesis. Additionally, metabolism markers of the murine models will be analyzed to infer systemic alterations due to the knockout.
The osteokine profile will continue to be developed over diseases progression to identify early targets (osteokines) to be pursued for prediction or early diagnosis of energy homeostasis perturbation before apparent disease manifests.
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| Causes of Carryover |
Delay because the transcriptomic data analysis company delayed providing the service required in the fascial year FY2022, because the sequencer was over occupied. The service will be billed in FY2023.
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