Involvement of fibroblast growth factor 23 in bone and mineral metabolism and its disorders

• Project/Area Number: 18390274
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: FUKUMOTO Seiji The University of Tokyo, 医学部・附属病院, 講師 (30202287)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥2,490,000); Fiscal Year 2008: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2006: ¥6,500,000 (Direct Cost: ¥6,500,000)
• Keywords: 骨軟化症 / ホルモン / 低リン血症 / 高リン血症 / FGF / Klotho / FGF受容体 / プロテアーゼ / FGF23 / O型糖鎖 / 翻訳後修飾 / 腫瘍状石灰化症 / 腫瘍性骨軟化症

Research Abstract

血中リン濃度の異常は、くる病/骨軟化症や異所性石灰化の原因となる。従って生体には、リン濃度を一定の範囲に維持する機構が備わっているものと考えられる。線維芽細胞増殖因子23(FGF23)は、血中リン濃度を低下させるように作用する液性因子である。本研究では、FGF23 の作用にKlotho が必要であること、FGF23 作用障害により高リン血症性疾患が惹起されることなどから、FGF23 が血中リン濃度を調節するホルモンであることが明らかとなった。

Research Products

• [Journal Article] Anti-FGF23 neutralizing antibodies demonstrate the physiological role and structural features of FGF23 (2008)
  • Author(s): Yamazaki Y, Tamada T, Kasai N, Urakawa I, Aono Y, Hasegawa H, Fujita T, Kuroki R, Yamashita T, Fukumoto S, Shimada T
  • Journal Title: J Bone Miner Res 23 Pages: 1509-1518
• [Journal Article] Physiological regulation and disorders of phosphate metabolism-Pivotal role of fibroblast growth factor 23- (2008)
  • Author(s): Fukumoto S
  • Journal Title: Intern Med 47 Pages: 337-343
  • NAID: 130000079690
• [Journal Article] Actions and mode of actions of FGF19 subfamily members (2008)
  • Author(s): Fukumoto S
  • Journal Title: Endocr J 55 Pages: 23-31
  • NAID: 10021264366
• [Journal Article] Clinical usefulness of measurement of fibroblast growth factor 23(FGF23)in hypophosphatemic patients-Proposal of diagnostic criteria using FGF23 measurement- (2008)
  • Author(s): Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugimoto T, Yamauchi M, Michigami T, Matsumoto T
  • Journal Title: Bone 42 Pages: 1235-1239
• [Journal Article] Anti-FGF23 neutralizing antibodies demonstrate the physiological role and structural features of FGF23 (2008)
  • Author(s): Yamazaki Y, et al.
  • Journal Title: J Bone Miner Res 23 Pages: 1509-1518
  • Peer Reviewed
• [Journal Article] Clinical usefulness of measurement of fibroblast growth factor 23 (FGF 23) in hypophosphatemic patients - Proposal of diagnostic criteria using FGF23 measurement- (2008)
  • Author(s): Endo I, et al.
  • Journal Title: Bone 42 Pages: 1235-1239
  • Peer Reviewed
• [Journal Article] Physiological regulation and disorders of phosphate metabolism-Pivotalrole of fibroblast growth factor 23- (2008)
  • Author(s): Fukumoto S
  • Journal Title: Intern Med 47 Pages: 337-343
  • Peer Reviewed
• [Journal Article] Fibroblast growth factor-23(FGF23)in patients with transient hypoparathyroidism : Its important role in serum phosphate regulation (2007)
  • Author(s): Yamashita H, Yamazaki Y, Hasegawa H, Yamashita T, Fukumoto S, Shigematsu T, Kazama JJ, Fukagawa M, Noguchi S
  • Journal Title: Endocr J 54 Pages: 465-470
  • NAID: 130004770044
• [Journal Article] Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in human (2007)
  • Author(s): Ito N, Fukumoto S, Takeuchi Y, Takeda S, Suzuki H, Yamashita T, Fujita T
  • Journal Title: J Bone Miner Metab 25 Pages: 419-422
  • NAID: 10024125586
• [Journal Article] Fibroblast growth factor (FGF)23 in patients with acromegaly (2007)
  • Author(s): Ito N, Fukumoto S, Taguchi M, Takeshita A, Takeuchi Y, Yamada S, Fujita T
  • Journal Title: Endocr J 54 Pages: 481-484
  • NAID: 130004770047
• [Journal Article] FGF23 is a hormone regulating phosphate metabolism-Unique biological characteristics of FGF23- (2007)
  • Author(s): Fukumoto S, Yamashita T
  • Journal Title: Bone 40 Pages: 1190-1195
• [Journal Article] Hyperostosis-hyperphosphatemia syndrome : A congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23 (2007)
  • Author(s): Frishberg Y, Ito N, Rinat C, Yamazaki Y, Feinstein S, Urakawa I, Navon-Elkan P, Becker-Cohen R, Yamashita T, Araya K, Igarashi T, Fujita T, Fukumoto S
  • Journal Title: J Bone Miner Res 27 Pages: 235-242
• [Journal Article] Fibroblast growth factor(FGF)23 in patients with acromegaly (2007)
  • Author(s): Ito N, et. al.
  • Journal Title: Endocr J 54 Pages: 481-484
  • Peer Reviewed
• [Journal Article] Effect of acute changes of serum phosphate on fibroblast growth factor FGF23 1evels in human (2007)
  • Author(s): Ito N, et. al.
  • Journal Title: J Bone Miner Metab 25 Pages: 419-422
  • Peer Reviewed
• [Journal Article] Hyperostosis - hyperphosphatemia syndrome : A congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23 (2007)
  • Author(s): Frishberg Y, et al.
  • Journal Title: J Bone Miner Res 27(2) Pages: 235-242
• [Journal Article] FGF23 is a hormone regulating phosphate metabolism-Unique biological characteristics of FGF23- (2007)
  • Author(s): Fukumoto S, et al.
  • Journal Title: Bone 40(5) Pages: 1190-1195
• [Journal Article] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006)
  • Author(s): Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T
  • Journal Title: Nature 444 Pages: 770-774
• [Journal Article] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006)
  • Author(s): Urakawa I, et al.
  • Journal Title: Nature 444(7120) Pages: 770-774
• [Journal Article] Bone as an endocrine organ
  • Author(s): Fukumoto S, Martin TJ
  • Journal Title: Trends Endocrinol Metab (in press)
  • NAID: 10025632854
• [Journal Article] The role of bone in phosphate metabolism
  • Author(s): Fukumoto S.
  • Journal Title: Mol Cell Endocrinol (in press)
• [Journal Article] The role of bone in phosphate metabolism
  • Author(s): Fukumoto S
  • Journal Title: Mol Cell Endocrinol (in press)
  • Peer Reviewed
• [Presentation] Significance of O-linked glycosylation of FGF23 protein (2008)
  • Author(s): Suzuki H, et al.
  • Organizer: Thirtieth Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2008-09-13
• [Presentation] Rare cases of X-linked hypophosphatemic rickets/osteomalacia mimicking autosomal recessive hypophosphatemic rickets/osteomalacia (2008)
  • Author(s): Saito T, Suzuki H, Ito N, Igarashi T, Fukumoto S, Fujita T
  • Organizer: Thirtieth Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Montreal
  • Year and Date: 2008-09-12
• [Presentation] Analysis and importance of glycosylation status in FGF23 protein (2007)
  • Author(s): Suzuki H, Fukumoto S, Ito N, Fujita T
  • Place of Presentation: Honolulu
  • Year and Date: 2007-09-19
• [Presentation] Analysis and importance of glycosylation status in FGF23 protein (2007)
  • Author(s): Suzuki H, et. al.
  • Organizer: Twenty-Ninth Annual Meeting of the American Socie fbr Bone and Mineral Research
  • Place of Presentation: HonolUlu,USA
  • Year and Date: 2007-09-19
• [Presentation] O-Linked Glycosylation by ppGaNTase-T3 Prevents Processing of Fibroblast Growth Factor (FGF)23 (2006)
  • Author(s): Ito N, Fukumoto S, Yamashita T, Frishberg Y, Fujita T
  • Organizer: Twenty-Eighth Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Philadelphia
  • Year and Date: 2006-09-16