The mechanism of BRONJ development by inflammation: The role of phosphate transporters.

• Project/Area Number: 16K20556
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: Kiyama Tomomi 東北大学, 歯学研究科, 助教 (40756011)
• Research Collaborator: KAWAI Toshihisa
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ビスホスホネート / トランスポーター / 顎骨壊死 / リン酸トランスポーター

Outline of Final Research Achievements

The aim of this project is to investigate the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ), by elucidating the mechanism of bisphosphonate’s cellular uptake, and the interrelationship between the transport mechanism and the inflammation. As the results, phosphate transporter SLC34 may be associated with the bisphosphonate’s cellular uptake and the transporter is increased with inflammation.
Therefore, there is the possibility that the inhibitor of phosphate transporter SLC34 can be useful for the treatment or prevention of BRONJ development.

Research Products

• [Int'l Joint Research] Ｔｈｅ Ｆｏｒｓｙｔｈ Ｉｎｓｔｉｔｕｔｅ(米国)
• [Journal Article] Phosphonocarboxylates Can Protect Mice against the Inflammatory and Necrotic Side Effects of Nitrogen-Containing Bisphosphonates by Inhibiting Their Entry into Cells <i>via</i> Phosphate Transporters (2016)
  • Author(s): Kiyama T, Tsuchiya M, Okada S, Oizumi T, Yamaguchi K, Sasaki K, Sugawara S, Endo Y.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 5 Pages: 712-720
  • DOI: 10.1248/bpb.b15-00770
  • NAID: 130005149275
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Possible pathogenic engagement of soluble Semaphorin 4D produced by γδT cells in medication-related osteonecrosis of the jaw (MRONJ). (2016)
  • Author(s): Movila, A., Mawardi, H., Nishimura, K., Kiyama, T., Egashira, K., Kim, JY., Villa, A., Sasaki, H., Woo, SB., Kawai, T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 480 Issue: 1 Pages: 42-47
  • DOI: 10.1016/j.bbrc.2016.10.012
  • Peer Reviewed / Int'l Joint Research
• [Presentation] リン酸トランスポーター阻害剤によるBRONJ発症抑制機序の解明 (2016)
  • Author(s): 木山朋美、河井敬久、遠藤康男、佐々木啓一
  • Organizer: 第125回日本補綴歯科学会学術大会
  • Place of Presentation: ＡＮＡクラウンプラザホテル金沢（石川県・金沢）
  • Year and Date: 2016-07-08