The elucidation of molecular mechanisms of amelogenesis by epitherial-specific Runx knockout mouse

• Project/Area Number: 22390390
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Tottori University (2012); Okayama University (2010-2011)
• Principal Investigator: HONJO Tadashi 鳥取大学, 医学部附属病院, 助教 (10379844)
• Co-Investigator(Kenkyū-buntansha): YAMASHIRO Takashi 岡山大学, 大学院医歯薬学総合研究科, 教授 (70294428) ; KAMIOKA Hiroshi 岡山大学, 大学院・医歯薬学総合研究科, 準教授 (80253219) ; 黒坂 寛 岡山大学, 大学院・医歯薬学総合研究科, 助教 (20509369) ; 中川 一路 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (70294113)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: Runx1, Cbfb / エナメル芽細胞 / 遺伝子改変動物 / エナメル質 / Runxシグナリング / Runx1 / Cbvb / cbfb / runx1 / Runx / Cbfb / 歯原性上皮

Research Abstract

Targeted deletion of Runx genes has revealed distinct roles for these proteins in development. Here, we report that epithelial Runx genes are involved in regulation of ameloblastdifferentiation. We analyzed the functional role of Cbfb and Runx1 in the enamel formation invivo, using a conditional genetic approach in which the Cbfb and Runx1 gene was inactivated in mouse epithelial cells(K14-Cre/Cbfbfl/fl, K14-Cre/Runx1 fl/fl). We found that mice deficient in epithelial Cbfb and Runx1 resulted in enamel aplasia in the incisors and in hypoplasia in the molars. The present results provide the genetic evidence that Runx1 and Cbfb genes function in the enamel formation in developing molar and incisors.

Research Products

• [Journal Article] Ex vivo real-time observation of Ca(2+) signaling in living bone in response to shear stressapplied on the bone surface (2013)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka HKawanabe N, Hayano S, Balam TA, Naruse K, ,Yamashiro T
  • Journal Title: Bone. Volume: 53(1)
• [Journal Article] Cartilage-Specific Over-Expression of CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Stimulates Insulin-Like Growth Factor Expression and Bone Growth (2013)
  • Author(s): Tomita N, Hattori T, Itoh S, Aoyama E, Yao M, Yamashiro T,Takigawa M
  • Journal Title: PLoS One Volume: 8(3)
  • NAID: 120005345532
• [Journal Article] Sugawara Y, Kamioka H, Ishihara Y, Fujisawa N, Kawanabe N, Yamashiro T (2013)
  • Author(s): Sugawara Y, Kamioka H, Ishihara Y, Fujisawa N, Kawanabe N, Yamashiro T
  • Journal Title: Bone. Volume: 52(1) Pages: 189-96
• [Journal Article] Ex vivo real-time observation of Ca(2+) signaling in living bone in response to shear stress applied on the bone surface. (2013)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Hayano S, Balam TA, Naruse K, Yamashiro T.
  • Journal Title: Bone. Volume: 53(1) Pages: 204-15
  • Peer Reviewed
• [Journal Article] Cartilage-Specific Over-Expression of CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Stimulates Insulin-Like Growth Factor Expression and Bone Growth. (2013)
  • Author(s): Tomita N, Hattori T, Itoh S, Aoyama E, Yao M, Yamashiro T, Takigawa M.
  • Journal Title: PLoS One. Volume: 8(3)
  • NAID: 120005345532
  • Peer Reviewed
• [Journal Article] The early mouse 3D osteocyte network in the presence and absence of mechanical loading. (2013)
  • Author(s): Sugawara Y, Kamioka H, Ishihara Y, Fujisawa N, Kawanabe N, Yamashiro T.
  • Journal Title: Bone. Volume: 52(1) Pages: 189-96
  • Peer Reviewed
• [Journal Article] Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress (2012)
  • Author(s): onjo T, Kubota S, Kamioka H, Sugawara Y, Ishihara Y, Yamashiro T, Takigawa M, Takano-Yamamoto T
  • Journal Title: J Cell Commun Signal Volume: 6(4) Pages: 225-32
• [Journal Article] SSEA-4 is a marker of human deciduous periodontal ligament stem cells (2012)
  • Author(s): Fukushima H, Kawanabe N, Murata S, Ishihara Y, Yanagita T, Balam TA, Yamashiro T
  • Journal Title: J Dent Res Volume: 91(10) Pages: 955-60
• [Journal Article] Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model (2012)
  • Author(s): Kamioka H, Kameo Y, Imai Y, Bakker AD, Bacabac RG, Yamada N, Takaoka A, Yamashiro T, Adachi T, Klein-NulendJ.
  • Journal Title: IntegrBiol (Camb) Volume: 4(10) Pages: 1198-206
• [Journal Article] Roles of heparan sulfate sulfation in dentinogenesis (2012)
  • Author(s): Hayano S, Kurosaka H, Yanagita T, Kalus I, Milz F, Ishihara Y, Islam MN, Kawanabe N, Saito M, Kamioka H, Adachi T, Dierks T, Yamashiro T
  • Journal Title: J Biol Chem Volume: 287(15): Pages: 12217-29
• [Journal Article] In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone (2012)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Kurosaka H, Naruse K, Yamashiro T
  • Journal Title: Bone. Volume: 50(4) Pages: 842-52
• [Journal Article] Stage-specific embryonic antigen-4 identifies human dental pulp stem cells (2012)
  • Author(s): Kawanabe N, Murata S, Fukushima H, Ishihara Y, Yanagita T, Yanagita E, Ono M, Kurosaka H, Kamioka H, Itoh T, Kuboki T, Yamashiro T
  • Journal Title: Exp Cell Res Volume: 318(5) Pages: 453-63
• [Journal Article] Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress. (2012)
  • Author(s): Honjo T, Kubota S, Kamioka H, Sugawara Y, Ishihara Y, Yamashiro T, Takigawa M, Takano-Yamamoto T.
  • Journal Title: J Cell Commun Signal. Volume: 6(4) Pages: 225-32
  • Peer Reviewed
• [Journal Article] SSEA-4 is a marker of human deciduous periodontal ligament stem cells. (2012)
  • Author(s): Fukushima H, Kawanabe N, Murata S, Ishihara Y, Yanagita T, Balam TA, Yamashiro T.
  • Journal Title: J Dent Res. Volume: 91(10) Pages: 955-60
  • Peer Reviewed
• [Journal Article] Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model. (2012)
  • Author(s): Kamioka H, Kameo Y, Imai Y, Bakker AD, Bacabac RG, Yamada N, Takaoka A, Yamashiro T, Adachi T, Klein-Nulend J.
  • Journal Title: IntegrBiol (Camb). Volume: 4(10) Pages: 1198-206
  • Peer Reviewed
• [Journal Article] Stage-specific embryonic antigen-4 identifies human dental pulp stem cells. (2012)
  • Author(s): Kawanabe N, Murata S, Fukushima H, Ishihara Y, Yanagita T, Yanagita E, Ono M, Kurosaka H, Kamioka H, Itoh T, Kuboki T, Yamashiro T.
  • Journal Title: Exp Cell Res. Volume: 10;318(5) Pages: 453-63
  • Peer Reviewed
• [Journal Article] Roles of heparan sulfate sulfation in dentinogenesis. (2012)
  • Author(s): Hayano S, Kurosaka H, Yanagita T, Kalus I, Milz F, Ishihara Y, Islam MN, Kawanabe N, Saito M, Kamioka H, Adachi T, Dierks T, Yamashiro T.
  • Journal Title: J Biol Chem. Volume: 287(15) Pages: 12217-29
  • Peer Reviewed
• [Journal Article] In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone. (2012)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Kurosaka H, Naruse K, Yamashiro T.
  • Journal Title: Bone. Volume: 50(4) Pages: 842-52
• [Journal Article] Core binding factor beta functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors (2012)
  • Author(s): Kurosaka H, Isiam MN, Kuremoto K, Hayano S, Nakamura M, Kawanabe N, Yanagita T, Rice DP, Harada H, Taniuchi I, Yamashiro T
  • Journal Title: Stem Cells Volume: 29(11) Pages: 1792-803
  • Peer Reviewed
• [Journal Article] A case report of multidisciplinary treatment of an adult patient with bilateral cleft lip and palate (2011)
  • Author(s): Fukunaga T, Honjo T, Sakai Y, Sasaki K, Takano-Yamamoto T, Yamashiro T
  • Journal Title: Cleft Palate Craniofac J
• [Journal Article] Core binding factor beta functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors (2011)
  • Author(s): Kurosaka H, Islam MN, Kuremoto K, Hayano S, Nakamura M, Kawanabe N, Yanagita T, Rice DP, Harada H, Taniuchi I, Yamashiro T
  • Journal Title: Stem Cells Volume: 29(11) Pages: 1792-803
• [Journal Article] The three-dimensional morphometry and cell-cell communication of the osteocyte network in chick and mouse embryonic calvaria (2011)
  • Author(s): Sugawara Y, Ando R, Kamioka H, Ishihara Y, Honjo T, Kawanabe N, Kurosaka H, Takano-Yamamoto T, Yamashiro T.
  • Journal Title: Calcif Tissue Int Volume: 88(5) Pages: 416-24
• [Presentation] Stage-specific embryonic antigen-4 is a marker of human deciduous periodontalligament stem cells (2012)
  • Author(s): Kawanab N, Fukushim H, Murata S,Ishihara Y, Yanagit T, Balam TA, Yamashiro T
  • Organizer: 34thAnnual Meeting of the AmericanSociety of Bone and Mineral Research
  • Place of Presentation: Minneapolis, US
• [Presentation] Live imaging of fluid flow-induced Ca_2+signaling of osteoblasts and osteocytes in bone: implications for gap junctional intercellular communication (2012)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Naruse K, Yamashiro T
  • Organizer: 34th Annual Meeting of the American society of bone and mineral research
  • Place of Presentation: Minneapolis, USA
• [Presentation] Stage-specific embryonic antigen-4 is a marker of human deciduous periodontal ligament stem cells. (2012)
  • Author(s): Kawanab N, Fukushima H, Murata S, Ishihara Y, Yanagit T, Balam TA, Yamashiro T.
  • Organizer: 34th Annual Meeting of the American Society of Bone and Mineral Research
  • Place of Presentation: Minneapolis, 米国.
• [Presentation] Live imaging of fluid flow-induced Ca2+ signaling of osteoblasts and osteocytes in bone: implications for gap junctional intercellular communication. (2012)
  • Author(s): Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Naruse K, Yamashiro T.
  • Organizer: 34th Annual Meeting of the American Society of Bone and Mineral Research
  • Place of Presentation: Minneapolis, 米国.
• [Presentation] Cbfb は切歯の上皮幹細胞の維持と, 増殖と分化の領域形成に関与する.サテライトシンポジウム3・歯の幹細胞を考える. (2011)
  • Author(s): 山城隆
  • Organizer: 第53回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岐阜.
  • Year and Date: 2011-09-30
• [Presentation] Cbfbは切歯の上皮幹細胞の維持と、増殖と分化の領域形成に関与する (2011)
  • Author(s): 山城隆
  • Organizer: 第53回歯科基礎医学会学術大会ならびに総会2011、サテライトシンポジウム歯の幹細胞を考える
  • Place of Presentation: 岐阜市
  • Year and Date: 2011-09-30
• [Presentation] Core binding factorβ(Cbfβ) functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors (2011)
  • Author(s): Yamashiro T
  • Organizer: 18thInternational RunxWorkshop
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2011-08-15
• [Presentation] Core binding factor beta (Cbfb) functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors (2011)
  • Author(s): Kurosaka H, Islam MN, Kuremoto K,Hayano S, Nakamura M, Kawanabe N, Yanagita T, Rice DP, Harada H, Taniuchi I, Yamashiro T
  • Organizer: Gordon Research Conference on Bones and Teeth
  • Place of Presentation: Les Diablerets, Switzerland
• [Presentation] 歯の発生及びエナメル芽細胞分化におけるcore-binding factor β(Cbfb)の役割について (2010)
  • Author(s): 黒坂寛、早野暁、山城隆
  • Organizer: 第69回日本矯正歯科学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 歯の発生及びエナメル芽細胞分化におけるcore-binding factor β(Cbfb)の役割について (2010)
  • Author(s): 黒坂寛, 早野暁, 呉本晃一, 原田英光, 山城隆
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: タワーホール船堀