Periodontal regenerative effects by inhibition of Sprouty2 protein in periodontal ligament cells

• Project/Area Number: 26893196
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Periodontology
• Research Institution: Kyushu University
• Principal Investigator: Tanaka Urara 九州大学, 歯学研究科(研究院), 研究員 (50734993)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Spry2 / proliferation / migration / bFGF / EGF / periodontal regeneration / periodontal ligament / cell migration / Rac / Sprouty2

Outline of Final Research Achievements

In this study, we investigated how Spry2 inhibition affects the cellular physiology of periodontal ligament (PDL) cells. ERK1/2 activation and proliferation of 1-17 PDL cells were significantly upregulated by the addition of Spry2 siRNA in the presence of bFGF and EGF. In addition, Spry2 siRNA reduced transcription of osteogenesis-related genes and ALP staining relative to control cells. Furthermore, it increased AKT/phosphatidylinositol 3-kinase (PI3K) phosphorylation; consequently, Rac1 but not Cdc42 was activated, thereby promoting lamellipodia formation, cell proliferation, and migration after stimulation by bFGF and EGF. In conclusion, Spry2 combined with bFGF and EGF stimulation reduced PDL cell migration and proliferation with inducing osteoblastic differentiation. These in vitro findings may provide a molecular basis for novel therapeutic approaches for establishing periodontal tissue regeneration.

Research Products

• [Journal Article] Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ and Porphyromonas gingivalis lipopolysaccharide. (2016)
  • Author(s): Atomura R, Sanui T*, Fukuda T, Tanaka U, Toyoda K, Taketomi T, Yamamichi K, Akiyama H, Nishimura F
  • Journal Title: Immunity, Inflammation and Disease Volume: 4（1） Issue: 1 Pages: 98-110
  • DOI: 10.1002/iid3.99
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Grp78 is critical for amelogenin-induced cell migration in a multipotent clonal human periodontal ligament cell line. (2016)
  • Author(s): Toyoda K, Fukuda T, Sanui T*, Tanaka U, Yamamichi K, Atomura R, Maeda H, Tomokiyo A, Taketomi T, Uchiumi T, Nishimura F
  • Journal Title: Journal of Cellular Physiology Volume: 231 Issue: 2 Pages: 414-427
  • DOI: 10.1002/jcp.25087
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tyrosine 55 Mutation of Spry2 Induces Proliferation and Differentiation of Osteoblasts through bFGF and EGF Stimulation but Inhibits Proliferation of Gingival Epithelial Cells (2015)
  • Author(s): Sanui T, Tanaka U, Fukuda T, Toyoda K, Taketomi T, Atomura R, Yamamichi K , Nishimura F.
  • Journal Title: Journal of Cellular Biochemistry Volume: 116 Issue: 4 Pages: 628-639
  • DOI: 10.1002/jcb.25014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spry2 is a novel therapeutic target for periodontal tissue regeneration through fibroblast growth factor receptor signaling and epidermal growth factor signaling. (2015)
  • Author(s): Sanui T, Fukuda T, Tanaka U, Toyoda K, Taketomi T, Nishimura F.
  • Journal Title: Receptors and Clinical Investigation Volume: 2
  • DOI: 10.14800/rci.597
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Molecular basis of amelogenin-induced periodontal tissue regeneration (2016)
  • Author(s): Takao Fukuda, Terukazu Sanui, Kyosuke Toyoda, Urara Tanaka, Kensuke Yamamichi, Ryo Atomura, Hajime Akiyama, Fusanori Nishimura
  • Organizer: 口腔から健康長寿を支えるプロジェクト推進に向けた研究拠点構築プログラム2nd Symposium
  • Place of Presentation: 福岡リーセントホテル
  • Year and Date: 2016-02-28
  • Int'l Joint Research
• [Presentation] Grp78 is critical for amelogenin-induced cell migration in PDL cells (2015)
  • Author(s): Takao Fukuda, Kyosuke Toyoda, Terukazu Sanui, Urara Tanaka, Kensuke Yamamichi, Ryo Atomura, Takaharu Taketomi, Fusanori Nishimura
  • Organizer: Penn Periodontal Conference 2015
  • Place of Presentation: 西日本Penn Dental Medicine in Philadelphia, Pennsylvania
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] Inhibition of Sprouty2 Regulates Cell Functions in Periodontal Ligament Cells (2015)
  • Author(s): Urara Tanaka, Terukazu Sanui, Takao Fukuda, Kyosuke Toyoda, Ryo Atomura, Kensuke Yamamichi, Fusanori Nishimura
  • Organizer: Penn Periodontal Conference 2015
  • Place of Presentation: Penn Dental Medicine in Philadelphia, Pennsylvania
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] 新規に同定したアメロジェニン会合蛋白Grp78がヒト歯根膜幹細胞/前駆細胞株の機能に及ぼす役割の検討 (2015)
  • Author(s): 豊田敬介、福田隆男、讃井彰一、後村亮、山道研介、田中麗、西村英紀
  • Organizer: 平成27年度 第58回春季日本歯周病学会学術大会
  • Place of Presentation: 幕張メッセ 国際会議場・国際展示場 ホール7
  • Year and Date: 2015-05-16
• [Presentation] Sprouty2 regulates cell proliferation and migration in periodontal ligament cells. (2015)
  • Author(s): Urara Tanaka, Terukazu Sanui, Takao Fukuda, Kyosuke Toyoda, Takaharu Taketomi, Ryo Atomura, Kensuke Yamamichi and Fusanori Nishimura
  • Organizer: 93rd General Session & Exhibition of the International Association for Dental Research
  • Place of Presentation: Haynes Convention Center, Boston, USA
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] The Effects of Spry2 in Osteoblasts and Gingival Epithelial Cells. (2015)
  • Author(s): T. Sanui, R. Atomura, U. Tanaka, T. Fukuda, K. Toyoda, K.Yamamichi, T. Taketomi, F. Nishimura
  • Organizer: 93rd General Session & Exhibition of the International Association for Dental Research
  • Place of Presentation: Haynes Convention Center, Boston, USA
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] Grp78 is Essential for Amelogenin-Induced Cell Migration in PDLSCs. (2015)
  • Author(s): T. Fukuda, R. Atomura, T. Kyosuke, K. Yamamichi, U. Tanaka, T. Sanui, T. Taketomi, F. Nishimura
  • Organizer: 93rd General Session & Exhibition of the International Association for Dental Research
  • Place of Presentation: Haynes Convention Center, Boston, USA
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] Grp78 is critical for amelogenin-induced cell migration in a human periodontal ligament stem/progenitor cell line. (2015)
  • Author(s): Kyosuke Toyoda, Takao Fukuda, Terukazu Sanui, Urara Tanaka,Ryo Atomura, Kensuke Yamamichi, and Fusanori Nishimura
  • Organizer: Kyudai Oral Bioscience (KOB) 2015
  • Place of Presentation: 福岡リーセントホテル、福岡市
  • Year and Date: 2015-02-28
• [Presentation] Sprouty2 Regulates Cell Proliferation and Migration in Periodontal Ligament Cells. (2015)
  • Author(s): Urara Tanaka, Terukazu Sanui, Takao Fukuda, Kyosuke Toyoda, Ryo Atomura, Kensuke Yamamichi, and Fusanori Nishimura.
  • Organizer: 頭脳循環Kick Off Symposium
  • Place of Presentation: 福岡リーセントホテル、福岡市
  • Year and Date: 2015-02-27
• [Presentation] Tyrosine 55 Mutation of Spry2 Induces Proliferation and Differentiation of Osteoblasts through bFGF and EGF Stimulation but Inhibits Proliferation of Gingival Epithelial Cells: Implications for Novel Biological Approach to Periodontal Regeneration. (2014)
  • Author(s): Terukazu Sanui, Urara Tanaka, Kyosuke Toyoda, Ryo Atomura, Takao Fukuda, Takaharu Taketomi, Kensuke Yamamichi and Fusanori Nishimura
  • Organizer: 62nd Annual Meeting of Japanese Association for Dental Research
  • Place of Presentation: KKRホテル大阪、大阪市
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] Amelogenin induces cell migration via Grp78 in PDL cells. (2014)
  • Author(s): Kyosuke Toyoda, Takao Fukuda, Ryo Atomura, Terukazu Sanui, Urara Tanaka, Takaharu Taketomi, Kensuke Yamamichi and Fusanori Nishimura
  • Organizer: 62nd Annual Meeting of Japanese Association for Dental Research
  • Place of Presentation: KKRホテル大阪、大阪市
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] アメロジェニンの生物学的活性の機序解明 (2014)
  • Author(s): 豊田敬介、後村亮、福田隆男、讃井彰一、山道研介、田中麗、西村英紀
  • Organizer: 平成26年度日本歯周病学会九州五大学日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: アクロス福岡、福岡市
  • Year and Date: 2014-11-16
• [Presentation] 新規に同定したアメロジェニン会合分子GRP78がヒト歯根膜細胞機能に果たす役割の検討 (2014)
  • Author(s): 豊田敬介、後村亮、福田隆男、讃井彰一、山道研介、田中麗、西村英紀
  • Organizer: 第58日本歯周病学会秋季学術大会
  • Place of Presentation: 神戸市国際展示場、神戸市
  • Year and Date: 2014-10-19
• [Remarks] 九州大学大学院歯学研究院口腔機能修復学講座歯周病学分野
  • URL: http://www.dent.kyushu-u.ac.jp/perio/