The paradox of calcium in bone and blood vessel induced by FGF23 signaling disruption
| Project/Area Number |
17K17079
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Morphological basic dentistry
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 骨基質石灰化 / FGF23/klotho / 骨芽細胞 / 骨細胞 / 細胞・組織 / FGF23 / 骨代謝 / 基質石灰化 |
|---|
| Outline of Final Research Achievements |
In this study, we have examined femora in FGF23 deficient mice to clarify the mechanisum of bone mineralization induced by disrupted FGF23/klotho signaling.
FGF23 deficient mice revealed a broad non-mineralized bone matrix despite highly-elevated serum concentration of Ca/Pi. Many matrix vesicles were localized in osteoid underneath ALP/ENPP1-positive osteoblasts, while few mineralized nodules were formed in FGF23 deficient osteoid. Furthermore, osteocytes in FGF23 deficient mice expressed abundunt SIBLING family proteins such as DMP-1 and osteopontin compared with control mice. It seems likely that the disrupted FGF23/klotho signaling may induce the disfunction of osteoblasts and osteocytes and the abnormal mineralization in bone.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、FGF23/klothoシグナル破綻によって誘導される骨基質石灰化異常の病理機序解明の一助を担うものである。骨基質石灰化は、全身性および局所性のカルシウム・リン代謝調節因子によって制御されており、複雑な機序で進行する。本研究成果は、全身性のリン調節因子であるFGF23/klothoシグナルの局所作用の可能性を示唆するものであり、基質石灰化制御機構の解明という基礎医学の発展のみならず、慢性腎臓病に伴う骨基質石灰化異常の病態解明や新規治療法の開発にも繋がる臨床研究の基盤として重要な学術的・社会的意義を有すると考えられる。
|
Report
(3 results)
Research Products
(20 results)
-
-
-
[Journal Article] Histochemical examination on periodontal tissues of Klotho-deficient mice fed with phosphate insufficient diet.2017
Author(s)
Hikone K., Hasegawa T., Tsuchiya E., Hongo H., Sasaki M., Yamamoto T., Kudo A., Oda K., Haraguchi M., Freitas PHL., Li M., Iida J., Amizuka N.
-
Journal Title
The Journal of Histochemistry and Cytochemistry
Volume: 65巻4号
Issue: 4
Pages: 207-221
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] <b>Chronological immunolocalization of sclerostin and FGF23 in the mouse metaphyseal trabecular and cortical </b><b>bone </b>2017
Author(s)
Sakurai A., Hasegawa T., Kudo A., Shen Z., Nagai T., Abe M., Yoshida T., Hongo H., Yamamoto T., Yamamoto T., Oda K., Freitas de PHL., Li M., Sano H., Amizuka N.
-
Journal Title
Biomedical Research
Volume: 38
Issue: 4
Pages: 257-267
DOI
NAID
ISSN
0388-6107, 1880-313X
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Ultrastructural and biochemical aspects of matrix vesicle-mediated mineralization.2017
Author(s)
Hasegawa T., Yamamoto T., Tsuchiya E., Hongo H., Tsuboi K., Kudo A., Abe M., Yoshida T., Nagai T., Khadiza N., Yokoyama A., Oda K., Ozawa H., Freitas de PHL., Li M., Amizuka N.
-
Journal Title
Japanese Dental Science Review
Volume: 53巻2号
Issue: 2
Pages: 34-45
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
[Journal Article] Cellular function of osteocytes in normal and aklotho-deficient mice.2017
Author(s)
Amizuka N., Hasegawa T., Yamamoto T., Mae T., Qiu Z., Abe M., Shen Z., Nagai T., Yokoyama A., Khadiza N., Haraguchi M., Yamamoto T., Freitas PHL., Li M.
-
Journal Title
Hokkaido Journal of Dental Science.
Volume: 38
Pages: 56-62
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
