Clarification of the function of TIMP3 in fracture healing and development of new fracture healing drug

• Project/Area Number: 21792077
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: HIASA Masahiro The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 助教 (90511337)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 破骨細胞 / 樹状細胞 / 骨折治癒 / 骨芽細胞

Research Abstract

Monocytes can give rise to osteoclasts (OCs), and dendritic cells (DCs), but these differentiation mechanism is unclear. We clarified that BMSCs up-modulate M-CSF receptor on monocytes through TIMP-3 elaborated by BMSCs to facilitate osteoclastogenesis and suppress DC differentiation, and that TIMP-3 expression is induced in OCs by themselves during osteoclastogenesis to further block TACE activity and enhance the surface expression of M-CSF receptor. This study demonstrated that the suppression of TACE-mediated shedding of M-CSF receptor by BMSCs may dysregulate monocyte differentiation towards OCs to cause bone resorption and anti-inflammatory response in bone remodeling.

Research Products

• [Journal Article] GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme (TACE). (2009)
  • Author(s): Hiasa M, Abe M, Nakano A, Oda A, AmouH, Kido S, Takeuchi K, Kagawa K, YataK, Hashimoto T, Ozaki S, Asaoka K,Tanaka E, Moriyama K, Matsumoto T.
  • Journal Title: Blood. 114(20) Pages: 4517-4526
  • Peer Reviewed
• [Journal Article] GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme(TACE). (2009)
  • Author(s): Hiasa M
  • Journal Title: Blood. 114(20) Pages: 4517-4526
  • Peer Reviewed
• [Presentation] ニッケルチタン合金の腐食とその生体為害性 (2010)
  • Author(s): 日浅雅博
  • Organizer: ナノバイオメディカル学会第2回大会
  • Place of Presentation: 大阪大学吹田キャンパス(大阪)
  • Year and Date: 2010-02-22
• [Presentation] Bone marrow stromal cells suppresses TACE-mediated M-CSR and RANK shedding to facilitate osteoclastogenesis and suppress DC differentiation from monocytes. (2010)
  • Author(s): Masahiro Hiasa, Masahiro Abe, et al.
  • Organizer: ASBMR.
  • Place of Presentation: Toronto.
• [Presentation] 骨髄間質細胞は単球のTACE 活性を抑制し破骨細胞を形成する (2010)
  • Author(s): 日浅雅博、安倍正博, ら
  • Organizer: 第72回日本血液学会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Presentation] 骨髄間質細胞は単球のTACE 活性を抑制し樹状細胞分化を抑制し破骨細胞分化を誘導する (2010)
  • Author(s): 日浅雅博、安倍正博, ら
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] Stroma inhibit DC differentiation through the suppression of M-CSFR shedding (2010)
  • Author(s): Masahiro Hiasa, Masahiro Abe, et al.
  • Organizer: 88th IADR.
  • Place of Presentation: Barcelona.
• [Presentation] Stroma inhibit DC differentiation through the suppression of M-CSFR sbedding (2010)
  • Author(s): Masahiro Hiasa, Masahiro Abe, et al.
  • Organizer: 88th IADR
  • Place of Presentation: Barcelona
• [Presentation] Bone marrow stromal cells suppresses TACE-mediated M-CSR and RANK shedding to facilitate osteoclastogenesis and suppress DC differentiation from monocytes. (2010)
  • Author(s): Masahiro Hiasa, Masahiro Abe, et al.
  • Organizer: ASBMR
  • Place of Presentation: Toronto
• [Presentation] 骨髄間質細胞は単球のTACE活性を抑制し樹状細胞分化を抑制し破骨細胞分化を誘導する (2010)
  • Author(s): 日浅雅博、安倍正博, ら
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] 骨髄間質細胞は単球のTACE活性を抑制し破骨細胞を形成する (2010)
  • Author(s): 日浅雅博、安倍正博, ら
  • Organizer: 第72回日本血液学会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Remarks] ホームページ等