Study of the FGF23-soluble Klotho axis in bone and dental diseases.
| Project/Area Number |
23592701
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
YOSHIKO YUJI 広島大学, 医歯薬保健学研究院, 教授 (20263709)
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Atsushi 藤田保健衛生大学, 医学部, 准教授 (90340265)
UCHIDA Soshi 産業医科大学, 医学部, 准教授 (60330990)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | FGF23 / 石灰化 / Phex / ASARM / 骨代謝 / KLotho / Klotho / ビタミンD / 骨細胞 |
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| Research Abstract |
We found that FG23, a phosphaturic factor, inhibits bone formation even though membrane Klotho (mKL), a coreceptor for FGF23 is not expressed in bone. It is known that mKL is cleaved and circulated as soluble KL (sKL). We confirmed that sKL supports the FGF23 effects on bone. Among FGF family members expressed in bone, FGF23, transcriptionally activated by 1,25(OH)2D3, stimulated transient activation of ERK1/2 only in mature steoblasts/osteocytes. This signaling downregulated Phex, with the resultant increase in the accumulation of ASARM peptide in bone. Administration of ASARM peptide decreased bone mineralization without affecting osteoblast proliferation and differentiation. These data describe a novel mechanism by which FGF23 regulates bone formation.
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Report
(4 results)
Research Products
(27 results)
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[Presentation] MEPE-ASARM, a substrate of Phex, decreases bone volume independently of serum phosphate levels2014
Author(s)
Sakurai Kaoru,Minamizaki Tomoko, Fujino Yoko, Takei Yuichiro, Yoshioka Hirotaka, Okada Mitsugu, Kozai Katsuyuki, Yoshiko Yuji
Organizer
The American Society for Bone Mineral Research 2014 Annual Meeting
Place of Presentation
Houston, USA
Related Report
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[Presentation] MEPE-ASARM, a substrate of Phex, decreases bone volume independently of serum phosphate levels.2014
Author(s)
Sakurai K, Minamizaki T, Fujino, Takei Y, Yoshioka H, Okada M, Kozai K, Yoshiko Y
Organizer
The American Society for Bone and Mineral Research 2014 Annual Meeting
Place of Presentation
Houston, TX, USA
Related Report
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[Presentation]2013
Author(s)
Minamizaki Tomoko, Konishi Yukiko, Sakurai Kaoru, Yoshioka Hirotaka, Kozai Katsuyuki, Yoshiko Yuji
Organizer
2nd Joint Meeting of the International Bone and Mineral Society and the Japanese Society for Bone and Mineral Research
Place of Presentation
Kobe
Related Report
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[Presentation] Imaging mass spectrometry-based molecular histology of bone shows the Implication of MEPE-ASARM for the Klotho-deficient phenotype.2013
Author(s)
Fujino Y, Minamizaki T, Sakurai K, Irie Y, Yoshioka H, Takei Y, Kozai K, Okada M, Yoshiko Y
Organizer
The American Society for Bone and Mineral Research 2013 Annual Meeting
Place of Presentation
Baltimore, MD, USA
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[Patent(Industrial Property Rights)] リン酸化ペプチド、硬組織および/または異所性石灰化抑制剤,抗体ならびに硬組織および/または異所性石灰化促進剤2011
Inventor(s)
吉子裕二,南崎朋子,吉岡広陽,平田伊佐雄,香西克之,前田憲彦,渡邊和晃,清藤勉
Industrial Property Rights Holder
広島大学,(株)ラフィーネインターナショナル,(株)免疫生物研究所種類
Industrial Property Rights Type
特許
Filing Date
2011-07-06
Related Report
Overseas
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