Elucidation of mechanisms underlying inflammation-induced LOX-1-dependent RANKL expression in osteoblasts

• Project/Area Number: 26870540
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry; Pathobiological dentistry/Dental radiology
• Research Institution: Meikai University
• Principal Investigator: Ito Junta 明海大学, 歯学部, 助教 (40609096)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: LOX-1 / 炎症性骨破壊 / 破骨細胞 / 骨芽細胞 / RANKL / 骨代謝 / 破骨細胞形成

Outline of Final Research Achievements

This study was aimed to clarify the relationship between osteoblastic RANKL expression and lectin-like oxidized LDL receptor-1 (LOX-1) in inflammatory bone destruction. I found that the RANKL expression in the inflamed bones was dependent on LOX-1 that was expressed in osteoblasts. In the co-culture of LOX-1-deleted osteoblasts and wild-type osteoclast precursors, the osteoclastogenesis induced by interleukin-1b and prostaglandin E2 decreased; this process occurred in parallel with the downregulation of osteoblastic RANKL expression. These results indicate that LOX-1-dependent osteoblastic RANKL expression in response to inflammation in bones promote osteoclast formation and bone resorption, suggesting that the blockage of LOX-1 could be a therapeutic target for inflammatory bone disease.

Research Products

• [Journal Article] Lectin-like oxidized low-density lipoprotein receptor-1 abrogation causes resistance to inflammatory bone destruction in mice, despite promoting osteoclastogenesis in the steady state. (2015)
  • Author(s): Nakayachi M, Ito J, Hayashida C, Ohyama Y, Kakino A, Okayasu M, Sato T, Ogasawara T, Kaneda T, Suda N, Sawamura T, Hakeda Y
  • Journal Title: BONE Volume: 75 Pages: 170-182
  • DOI: 10.1016/j.bone.2015.02.025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] レクチン様酸化LDL受容体-1 (LOX-1)欠損は定常状態の破骨細胞形成を促進するが、LPS誘導炎症性骨破壊には抵抗性を示す (2015)
  • Author(s): 伊東順太、林田千代美、大山洋子、佐藤卓也、羽毛田慈之
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 新潟（新潟）
  • Year and Date: 2015-09-11
• [Presentation] レクチン様酸化LDL受容体-1 (LOX-1)欠損は定常状態における破骨細胞形成を促進するが、LPS誘導炎症性骨破壊に抵抗性をもたらす (2015)
  • Author(s): 伊東順太、林田千代美、大山洋子、佐藤卓也、羽毛田慈之
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 新宿（東京）
  • Year and Date: 2015-07-23
• [Presentation] レクチン様酸化LDL受容体-1 (LOX-1)欠損マウスは骨量を減少させるが炎症性骨吸収に抵抗を示す (2014)
  • Author(s): 中谷地舞, 伊東順太, 岡安麻里, 須田直人, 羽毛田慈之
  • Organizer: 第73回日本矯正歯科学会大会
  • Place of Presentation: 幕張（千葉）
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] 炎症性骨破壊におけるRANKLの発現に対するlectin-like oxidized LDL receptor-1(LOX-1)の役割に関する研究 (2014)
  • Author(s): 伊東順太
  • Organizer: 明海歯科医学会第23回学術大会
  • Place of Presentation: 坂戸（埼玉）
  • Year and Date: 2014-06-05