FGF23 overexpression in bone in Hyp mice

• Project/Area Number: 16K09650
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka City University
• Principal Investigator: Imanishi Yasuo 大阪市立大学, 大学院医学研究科, 准教授 (50326253)
• Research Collaborator: MIYAOKA daichi ; HAYASHI noriyuki ; MAEDA tomomi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: X連鎖低リン血症性くる病 / くる病マウス / PHEX / 内科 / 細胞・組織

Outline of Final Research Achievements

X-linked hypophosphatemic rickets (XLH) is a disease caused by inactivating mutation of PHEX gene, however, precise pathway from PHEX to FGF23, a phosphaturic factor, was unknown. In this study, the role of dentin matrix protein-1 (DMP-1) was promoted for the signal pathway from PHEX to FGF23.

Academic Significance and Societal Importance of the Research Achievements

X連鎖低リン血症性くる病(XLH) は、本国における遺伝性くる病のなかでも頻度が非常に高く、その病態を研究することは、新規治療法開発においても非常に重要である。
今回の研究では、XLHの遺伝子異常によりリン利尿因子であるFGF-23が分泌されるまでの機序の一部にdentin matrix protein-1 (DMP-1)が関与していることを明らかにした。DMP-1の抑制によりFGF-23が上昇し、低リン血症を来すため、このDMP-1を介する細胞内情報伝達機構のさらなる検討を進めることで、新規治療法開発につながることが期待される。

Research Products

• [Journal Article] Attenuated Dentin Matrix Protein 1 Enhances Fibroblast Growth Factor 23 in Calvaria in Primary Hyperparathyroidism Model (2019)
  • Author(s): Nagata Yuki、Imanishi Yasuo、Ohara Masaya、Maeda-Tateishi Tomomi、Miyaoka Daichi、Hayashi Noriyuki、Kurajoh Masafumi、Emoto Masanori、Inaba Masaaki
  • Journal Title: Endocrinology Volume: 3 Issue: 5 Pages: 1348-1358
  • DOI: 10.1210/en.2019-00017
  • Peer Reviewed
• [Journal Article] Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency (2018)
  • Author(s): Miyaoka D.、Imanishi Y.、Ohara M.、Hayashi N.、Nagata Y.、Yamada S.、Mori K.、Emoto M.、Inaba M.
  • Journal Title: Osteoporosis International Volume: 30 Issue: 1 Pages: 241-249
  • DOI: 10.1007/s00198-018-4688-1
  • Peer Reviewed
• [Journal Article] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis (2018)
  • Author(s): Insogna Karl L、Briot Karine、Imel Erik A、Kamenick Peter、Ruppe Mary D、Portale Anthony A、Weber Thomas、Pitukcheewanont Pisit、Cheong Hae Il、Jan de Beur Suzanne、Imanishi Yasuo、et al.
  • Journal Title: Journal of Bone and Mineral Research Volume: 33 Issue: 8 Pages: 1383-1393
  • DOI: 10.1002/jbmr.3475
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Burosumab, an Anti-FGF23 Antibody, in Adults with X-Linked Hypophosphatemia (XLH) (2018)
  • Author(s): Anthony Portale; Karl Insogna; Erik Imel; Peter Kamenický; Yasuo Imanishi; Nobuaki Ito; Farzana Perwad; Lin Zhang; Christina Theodore-Oklota; Matt Mealiffe; Javier San Martin; Tom Carpenter
  • Organizer: ASN Kidney Week 2018
  • Int'l Joint Research
• [Presentation] Hypophosphatemic rickets and osteomalacia -Pathogenesis, diagnosis, and treatments (2018)
  • Author(s): Yasuo Imanishi
  • Organizer: 11th Edition of International Conference on Endocrinology and Diabetology
  • Int'l Joint Research / Invited
• [Presentation] 低リン血症性くる病・骨軟化症 －その過去・現在・未来－ (2018)
  • Author(s): 今西康雄
  • Organizer: 第38回日本骨形態計測学会
  • Invited