Identification of the molecular network regulating movement of Hedgehog proteins on cell surface during skeletal development

• Project/Area Number: 15K15732
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: Ohba Shinsuke 東京大学, 大学院医学系研究科(医学部), 准教授 (20466733)
• Co-Investigator(Kenkyū-buntansha): 鄭 雄一 東京大学, 大学院工学系研究科(工学部), 教授 (30345053)
• Research Collaborator: HOJO Hironori ; YAMAKAWA Akira ; ICHSAN Mochammad
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 発生・分化

Outline of Final Research Achievements

This study was aimed to understand the mechanism underlying the secretion and release of Hedgehog (Hh) proteins during mammalian skeletal development in an integrative manner. Mutant mice of genes that were involved in the secretion and cell surface regulation of Hh were analyzed. In addition, a new finding on Ihh-expressing cells are being obtained by integrative approach of mouse genetics and molecular biology. These findings will lead to integrative understanding of the secretion and cell surface regulation of Hh during skeletal development and contribute to the development of strategies that enhance the osteogenic effect of Hh.

Research Products

• [Int'l Joint Research] 南カリフォルニア大学(米国)
• [Int'l Joint Research] 南カリフォルニア大学(米国)
• [Journal Article] Multi-layered mutatin in hedgehog-related genes in Gorlin syndrome may affect the phenotype. (2017)
  • Author(s): Onodera S, Saito A, Hasegawa D, Watanabe K, Morita N, Nomura T, Shibahara T, Ohba S, Yamaguchi A, Azuma T
  • Journal Title: PLOS ONE Volume: 12 Issue: 9 Pages: e0184702-e0184702
  • DOI: 10.1371/journal.pone.0184702
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the gene-regulatory landscape in skeletal development and potential links to skeletal regeneration. (2017)
  • Author(s): Hojo H, Chung UI, Ohba S
  • Journal Title: Regenerative Therapy Volume: 6 Pages: 100-107
  • DOI: 10.1016/j.reth.2017.04.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An emerging regulatory landscape for skeletal development. (2016)
  • Author(s): Hojo H, McMahon AP, *Ohba S
  • Journal Title: Trends Genet Volume: 32 Issue: 12 Pages: 774-787
  • DOI: 10.1016/j.tig.2016.10.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Local administration of a hedgehog agonist accelerates fracture7healing in a mouse model. (2016)
  • Author(s): Kashiwagi M, Hojo H, Kitaura Y, Maeda Y, Aini H, Takato T, Chung U, Ohba S.
  • Journal Title: Biochem Biophys Res Comm Volume: 479 Issue: 4 Pages: 772-778
  • DOI: 10.1016/j.bbrc.2016.09.134
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] AP-1 family members act with Sox9 to promote chondrocyte hypertrophy. (2016)
  • Author(s): He X, Ohba S (co-first), Hojo H, McMahon AP
  • Journal Title: Development Volume: 143 Issue: 16 Pages: 3012-3023
  • DOI: 10.1242/dev.134502
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte. (2015)
  • Author(s): Ohba S, He X, Hojo H, McMahon AP
  • Journal Title: Cell Reports Volume: 12(2) Issue: 2 Pages: 229-243
  • DOI: 10.1016/j.celrep.2015.06.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 軟骨細胞におけるエンハンサーネットワークを介したIndian hedgehogの発現制御機構. (2017)
  • Author(s): 山川晃, 北條宏徳, 鄭雄一, 大庭伸介
  • Organizer: 第30回軟骨代謝学会
  • Place of Presentation: 京都市勧業館みやこめっせ（京都府京都市）
  • Year and Date: 2017-03-03
• [Presentation] A system level investigation to unravel mechanisms and potential direct targets of the osteogenic small molecule TH (2017)
  • Author(s): Ichsan M, Kanke K, Hojo H, Chung UI, Ohba S
  • Organizer: EMBL Conference: Mamalian Genetics and Genomics: From Molecular Mechanisms to Translational Applications.
  • Int'l Joint Research
• [Presentation] Oral administration of an egg yolk-derived peptide promotes fracture healing in a mouse model. (2017)
  • Author(s): Kitaura Y, Nakamura U, Sakashita M, Yamaghuchi M, Kim M, Chung UI, Ohba S
  • Organizer: 39th Annual Meeting of the American Society for Bone and Mineral Research
  • Int'l Joint Research
• [Presentation] 軟骨細胞特異的なIhhのエンハンサーの同定とSox9によるその活性化機構 (2017)
  • Author(s): 山川晃, 北條宏徳, 鄭雄一, 大庭伸介
  • Organizer: 第35回日本骨代謝学会学術集会
• [Presentation] Regulatory mechanisms underlying Ihh transcription in chondrocytes. (2016)
  • Author(s): Yamakawa A, Chung UI, Ohba S
  • Organizer: 38th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2016-09-16
  • Int'l Joint Research
• [Presentation] 骨形成の分子メカニズムとその骨再生への応用. (2016)
  • Author(s): 大庭伸介
  • Organizer: 日本セラミックス協会第29回秋季シンポジウム
  • Place of Presentation: 広島大学東広島キャンパス（広島県東広島市）
  • Year and Date: 2016-09-08
  • Invited
• [Presentation] 軟骨細胞におけるIndian hedgehogの発現制御機構. (2016)
  • Author(s): 山川晃, 鄭雄一, 大庭伸介
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-07-22
• [Presentation] 多能性幹細胞の段階的骨芽細胞分化誘導とその応用 (2015)
  • Author(s): 大庭伸介
  • Organizer: 第26回日本小児整形外科学会学術集会
  • Place of Presentation: 長良川国際会議場、岐阜市、岐阜県
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts using small molecules under defined conditions. (2015)
  • Author(s): Ohba S
  • Organizer: 2015 International Congress of Osteoporosis
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-11-29
  • Int'l Joint Research / Invited
• [Presentation] 医工の融合によるメディカルイノベータ－創出 (2015)
  • Author(s): 大庭伸介
  • Organizer: 第67回日本気管食道科学会総会・学術講演会
  • Place of Presentation: ザ・セレクトン福島、福島市、福島県
  • Year and Date: 2015-11-20
  • Invited
• [Presentation] Distinct modes of Sox9 action in the transcriptional regulation of developing mammalian chondrocytes (2015)
  • Author(s): Ohba S, He X, Hojo H, McMahon AP
  • Organizer: 37th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Seattle, U.S.A.
  • Year and Date: 2015-10-10
  • Int'l Joint Research
• [Presentation] 多能性幹細胞の段階的骨芽細胞分化誘導法の開発とその応用 (2015)
  • Author(s): 大庭伸介
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル、新宿区、東京都
  • Year and Date: 2015-07-23
  • Invited
• [Book] サイトカイン・増殖因子キーワード事典 第11章Hedgehogシグナル (2015)
  • Author(s): 大庭伸介, 鄭雄一
  • Total Pages: 420
  • Publisher: 羊土社
• [Remarks] 東京大学鄭雄一研究室大庭・鄭グループ ホームページ
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/ohba-tei/
• [Remarks] 東京大学 工学系研究科／医学系研究科 鄭雄一研究室 大庭・鄭グループ
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/ohba-tei/