Research for Development of Novel Bone Regeneration Drugs Focusing on Lansoprazole Activating RUNX2

• Project/Area Number: 18K16656
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kitasato University (2022); Nagoya University (2018-2021)
• Principal Investigator: Okabe Yuka 北里大学, 理学部, 助教 (20468383)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨形成促進 / 間葉系幹細胞 / RUNX2 / ランソプラゾール / 人工骨 / 骨形成 / 骨髄由来間葉系幹細胞 / 頭蓋骨欠損モデル / 骨再生

Outline of Final Research Achievements

It is known that Lansoprazole, a proton pump inhibitor, increases the expression and transcriptional activity of Runx2. This study aims to perform basic research on the development of a novel bone regeneration drug by combining hydrophilic lansoprazole with culture-bone marrow cells and artificial bone.
Treatment of commercially available human mesenchymal stem cells or patient-derived bone marrow stromal cells with 20 μM of hydrophilic lansoprazole for 24 hours promoted osteoblast differentiation and matrix calcium deposition in vitro.When hydrophilic lansoprazole-impregnated collagen sponges seeded with culture-bone marrow cells were implanted in a mouse skull defect model, bone formation was about 2-fold higher in the drug-treated group than in the control group. These results indicated that the combination of hydrophilic lansoprazole and culture-bone marrow cells in the bone matrix was found to apply to the improvement for repairing fractures and bone defects.

Academic Significance and Societal Importance of the Research Achievements

本研究は、すでに安全性が担保された既存薬によって現在の人工骨の欠点を補い、自家骨と同質な医療材料の創出を目指す研究である。既存役の適応外効能を見出し臨床応用につなげる創薬手法はドラッグリポジショニングと呼ばれ、副作用等のデータがそろっているため臨床応用までの時間と費用を大幅に短縮できる。
さらに歯科口腔外科領域でも、インプラントや口蓋裂の治療において歯槽骨の再生は必要不可欠である。したがって本研究の成果は、整形外科だけでなく歯科口腔外科領域にも応用可能であると考えらる。

Research Products

• [Journal Article] Efficacy of soluble lansoprazole-impregnated beta-tricalcium phosphate for bone regeneration (2022)
  • Author(s): Mishima Kenichi、Okabe Yuka Tsukagoshi、Mizuno Masaaki、Ohno Kinji、Kitoh Hiroshi、Imagama Shiro
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-022-25184-4
  • Peer Reviewed / Open Access
• [Journal Article] Biological characterization of adipose-derived regenerative cellsused for the treatment of stress urinary incontinence (2021)
  • Author(s): Yuka Tsukagoshi Okabe, Shinobu Shimizu, Yukihiro Suetake, Hisako Matsui-Hirai, Shizuka Hasegawa, Keisuke Takanari, Kazuhiro Toriyama, Yuzuru Kamei, Tokunori Yamamoto, Masaaki Mizuno, Momokazu Gotoh
  • Journal Title: International Journal of Urology Volume: 28 Issue: 1 Pages: 115-124
  • DOI: 10.1111/iju.14408
  • Peer Reviewed
• [Journal Article] A Novel Treatment with Stem Cells from Human Exfoliated Deciduous Teeth for Hypoxic-Ischemic Encephalopathy in Neonatal Rats (2020)
  • Author(s): Kitase Yuma、Sato Yoshiaki、Ueda Kazuto、Suzuki Toshihiko、Mikrogeorgiou Alkisti、Sugiyama Yuichiro、Matsubara Kohki、Tsukagoshi Okabe Yuka、Shimizu Shinobu、Hirata Hitoshi、Yukawa Hiroshi、Baba Yoshinobu、Tsuji Masahiro、Takahashi Yoshiyuki、Yamamoto Akihito、Hayakawa Masahiro
  • Journal Title: Stem Cells and Development Volume: 29 Issue: 2 Pages: 63-74
  • DOI: 10.1089/scd.2019.0221
  • Peer Reviewed / Open Access
• [Journal Article] Src inhibition attenuates polyglutamine-mediated neuromuscular degeneration in spinal and bulbar muscular atrophy (2019)
  • Author(s): Iida Madoka、Sahashi Kentaro、Kondo Naohide、Nakatsuji Hideaki、Tohnai Genki、Tsutsumi Yutaka、Noda Seiya、Murakami Ayuka、Onodera Kazunari、Okada Yohei、Nakatochi Masahiro、Tsukagoshi Okabe Yuka、Shimizu Shinobu、Mizuno Masaaki、Adachi Hiroaki、Okano Hideyuki、Sobue Gen、Katsuno Masahisa
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 4262-4262
  • DOI: 10.1038/s41467-019-12282-7
  • Peer Reviewed / Open Access
• [Presentation] 水溶性ランソプラゾールの局所投与による骨欠損修復の可能性 (2020)
  • Author(s): 岡部（塚越）由香、三島健一、加藤勝義、水野正明、鬼頭浩史、石黒直樹
  • Organizer: 第19回再生医療学会総会