uncovering the molecular mechanism of regulation of bone remodeling by micro RNA

• Project/Area Number: 21591936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SOTOME Shinichi 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (20401391)
• Co-Investigator(Kenkyū-buntansha): OKAWA Atsushi 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (30251507) ; YAMAUCHI Yuki 東京医科歯科大学, 医学部附属病院, 医員 (70422483)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Shu 慶應義塾大学, 医学部, 特任准教授 (30376727)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨 / 軟骨代謝学 / 骨代謝 / マイクロRNA / 骨芽細胞

Research Abstract

We tried to address the role of miRNAs, a well-known non-coding RNAs, as a physiological regulator of bone remodeling. Through comprehensive analyses, we identified multiple miRNAs whose expression was altered during osteoblastic differentiation. Subsequently, we focused on miR-206 and demonstrated that miR-206 suppresses osteblastic differentiation by regulating connexin 43 protein expression. Thus, we uncovered that miRNA is a physiological regulator of bone remodeling.

Research Products

• [Journal Article] Hybrid Grafting using Bone Marrow Aspirate combined with Porous beta-Tricalcium Phosphate and Trephine Bone for Lumbar Posterolateral Spinal Fusion : A Prospective, Comparative Study-Versus Local Bone Grafting (2012)
  • Author(s): Yamada T, Yoshii T, Sotome S, Yuasa M, Kato T, Arai Y, Kawabata S, Tomizawa S, Sakaki K, Hirai T, Shinomiya K, Okawa A
  • Journal Title: Spine Volume: 37(3)
• [Journal Article] Hybrid Grafting using Bone Marrow Aspirate combined with Porous beta-Tricalcium Phosphate and Trephine Bone for Lumbar Posterolateral Spinal Fusion : A Prospective, Comparative Study-Versus Local Bone Grafting- (2012)
  • Author(s): Yamada T, Yoshii T, Sotome S, Yuasa M, Kato T, Arai Y, Kawabata S, Tomizawa S, Sakaki K, Hirai T, Shinomiya K, Okawa A
  • Journal Title: Spine Volume: (In press) Issue: 3 Pages: 174-179
  • DOI: 10.1097/brs.0b013e3182269d64
  • Peer Reviewed
• [Journal Article] Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits (2011)
  • Author(s): Sugata Y, Sotome S, Yuasa M, Hirano M, Shinomiya K, Okawa A
  • Journal Title: The Journal of bone and joint surgery Volume: 93(4) Pages: 510-6
• [Journal Article] Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a rabbit bone defect model (2011)
  • Author(s): Sugata Y, Sotome S, Maehara H, Yuasa M, Masaoka T, Hirano M, Shinomiya K, Okawa A
  • Journal Title: Journal of Bone and Joint Surgery British Edition Volume: 93 Issue: 4 Pages: 510-516
  • DOI: 10.1302/0301-620x.93b4.25239
  • Peer Reviewed
• [Journal Article] Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen(HAp/Col) and fibroblast growth factor-2(FGF-2) (2010)
  • Author(s): Maehara H, Sotome S, Yoshii T, Torigoe I, Kawasaki Y, Sugata Y, Yuasa M, Hirano M, Mochizuki N, Kikuchi M, Shinomiya K, Okawa A
  • Journal Title: Journal of orthopaedic research Volume: 28(5) Pages: 677-86
• [Journal Article] Isolation of osteogenic progenitor cells from trabecular bone for bone tissue engineering (2010)
  • Author(s): Yoshii T, Sotome S, Torigoe I, Maehara H, Sugata Y, Yamada T, Shinomiya K, Okawa A
  • Journal Title: Tissue engineering. Part A Volume: 16(3) Pages: 933-42
• [Journal Article] Effects of gamma-ray irradiation on mechanical properties, osteoconductivity, and absorption of porous hydroxyapatite/collagen (2010)
  • Author(s): Kawasaki Y, Sotome S, Yoshii T, Torigoe I, Maehara H, Sugata Y, Hirano M, Mochizuki N, Shinomiya K, Okawa A
  • Journal Title: J Biomed Mater Res B Appl Biomater Volume: 92(2) Pages: 161-7
• [Journal Article] Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury (2010)
  • Author(s): Kusano K, Enomoto M, Hirai T, Tsoulfas P, Sotome S, Shinomiya K, Okawa A
  • Journal Title: Biochem Biophys Res Commun Volume: 393(4) Pages: 812-7
• [Journal Article] Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen (HAp/Col) and fibroblast growth factor-2 (FGF-2). (2010)
  • Author(s): Maehara H, Sotome S, Yoshii T, Torigoe I, Kawasaki Y, Sugata Y, Yuasa M, Hirano M, Mochizuki N, Kikuchi M, Shinomiya K, OkawaA.
  • Journal Title: Journal of orthopaedic research. Volume: 28 Pages: 677-86
  • Peer Reviewed
• [Journal Article] 骨のバイオマテリアル 人工骨 (2010)
  • Author(s): 早乙女進一, 四宮謙一, 大川淳
  • Journal Title: 綜合臨床 Volume: 59 Pages: 544-547
• [Journal Article] 臨床研究の活性化と再生医療産業化の促進 骨・関節領域(整形外科、歯科・口腔外科)の実施者からの提言 (2010)
  • Author(s): 大串始, 服部耕治, 牛田多加志, 星和人, 関矢一郎, 早乙女進一, ら
  • Journal Title: 再生医療 Volume: 9 Pages: 393-400
• [Journal Article] Fresh Bone Marrow Introduction into Porous Scaffolds Using a Simple Low-Pressure Loading Method for Effective Osteogenesis in a Rabbit Model (2009)
  • Author(s): Toshitaka Yoshii, Shinichi Sotome, Ichiro Torigoe, Akio Tsuchiya, Hidetsugu Maehara, Shizuko Ichinose, Kenichi Shinomiya
  • Journal Title: JOURNAL OF ORTHOPAEDIC RESEARCH Volume: 27 Pages: 1-7
• [Journal Article] Bone Regeneration with Autologous Plasma, Bone Marrow Stromal Cells, and Porous beta-Tricalcium Phosphate in Nonhuman Primates (2009)
  • Author(s): Torigoe I, Sotome S, Tsuchiya A, Yoshii T, Maehara H, Sugata Y, Ichinose S, Shinomiya K, Okawa A.
  • Journal Title: Tissue Eng Part A. Volume: 15(7) Pages: 1489-1499
• [Journal Article] A microRNA regulatory mechanism of osteoblast differentiation (2009)
  • Author(s): Inose, H., Ochi, H., Kimura, A., Fujita, K., Xu, R., Sato, S., Iwasaki, M., Sunamura, S., Takeuchi, Y., Fukumoto, S., Saito, K., Nakamura, T., Siomi, H., Ito, H., Arai, Y., Shinomiya, K.-i., and Takeda, S.
  • Journal Title: Proc Natl Acad Sci USA Volume: 106 Pages: 20794-20799
• [Journal Article] A microRNA regulatory mechanism of osteoblast differentiation (2009)
  • Author(s): Inose, Arai, Takeda, ら
  • Journal Title: Proceedings of the National Academy of Sciences USA 106 Pages: 20794-20799
  • Peer Reviewed
• [Journal Article] Effects of the systemic administration of alendronate on bone formationin a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a rabbit bone defect model
  • Author(s): Sugata Y, Sotome S, Maehara H, Yuasa M, Masaoka T, Hirano M, Shinomiya K, Okawa A.
  • Journal Title: Journal of Bone and Joint Surgery British Edition Volume: In press
  • Peer Reviewed
• [Presentation] BMPとデキサメサゾン併用による骨形成能に関する検討 (2010)
  • Author(s): 湯浅将人、早乙女進一、菅田祐美、正岡智和、山田剛史、四宮謙一、大川淳
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-14
• [Presentation] 温熱処理骨と骨髄由来間質細胞導入(3-TCPを用いた大型犬の骨欠損モデルにおける再生能 (2010)
  • Author(s): 小柳広高、阿江啓介、早乙女進一、前原秀二、菅田祐美、湯浅将人、山田剛史、正岡智和、船内雄生、四宮謙一、大川淳
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-14
• [Presentation] Regulation of osteoblast differenciation by microRNA 206 (2009)
  • Author(s): Fujita, Arai, Takedaら
  • Organizer: 第26回内藤コンファレンスオステオバイオロジー
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2009-11-05
• [Presentation] Regulation of osteoblast differenciation by microRNA 206. (2009)
  • Author(s): Fujita, Arai, Takeda, ら
  • Organizer: 第26回内藤コンファレンスオステオバイオロジ
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2009-11-05
• [Presentation] The Regulation of Osteoblast Differentiation by MicroRNA (2008)
  • Author(s): Inose, Arai, Takedaら
  • Organizer: American Society for Bone and Mineral Research Annual meeting
  • Place of Presentation: モントリオールカナダ
  • Year and Date: 2008-09-15
• [Presentation] The Regulation of Osteoblast Differentiation by MicroRNA (2008)
  • Author(s): Inose, Arai, Takeda, ら
  • Organizer: American Society for Bone and Mineral Research Annual meeting
  • Place of Presentation: モントリオール カナダ
  • Year and Date: 2008-09-15
• [Remarks]
  • URL: http://www.tmd.ac.jp/med/orth/sub/index.html
• [Patent(Industrial Property Rights)] リン酸カルシウム含有複合多孔体及びその製造方法 (2012)
  • Inventor(s): 西村祐介、四宮謙一、早乙女進一
  • Industrial Property Rights Holder: 西村祐介、四宮謙一、早乙女進一
  • Filing Date: 2012-02-17
• [Patent(Industrial Property Rights)] 骨移植片製造装置 (2010)
  • Inventor(s): 四宮謙一、早乙女進一, 他
  • Industrial Property Rights Holder: 四宮謙一、早乙女進一, 他
  • Filing Date: 2010-07-09