The roles and regulatory factors of cellular ligistics, autophagy maintaining the homeostasis of periodontal ligament.

• Project/Area Number: 26670887
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Kyushu University
• Principal Investigator: HARUYAMA NAOTO 九州大学, 歯学研究院, 准教授 (70359529)
• Co-Investigator(Kenkyū-buntansha): 寺尾 文恵 九州大学, 歯学研究院, 助教 (10510018) ; 安永 敦 九州大学, 歯学研究院, 共同研究員 (80515990)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯科矯正学 / オートファジー / 歯根膜 / 線維芽細胞 / アポトーシス / 低酸素 / 歯学 / 歯の移動 / メカニカルストレス / 細胞死

Outline of Final Research Achievements

In this study, we examined the autophagy inducible factors in periodontal ligament (PDL), and tried to clarify the relationship between autophagy and apoptotic cell death. First, we moved the maxillary first molar of GFP-LC3 transgenic mice, and examined the localization of autophagy marker, LC3 in the PDL. Autophagy (LC3) was induced in the compression side of PDL at 6 hours after initiating the tooth movement. The autophagy was found in the hypoxic area induced by tooth movement. Furthermore, autophagy was induced prior to the PDL cell apoptosis. In order to clarify the autophagy inducible factors in the PDL cells, low oxygen partial pressure were loaded to a human PDL fibroblast cell line, and resulted in increased cellular LC3 protein levels. These results suggest that the orthodontic tooth movement induces autophagy on compression side of PDL, and hypoxia is one of the critical inducers of autophagy.

Research Products

• [Journal Article] Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains. (2017)
  • Author(s): Arai C, Yoshizaki K, Miyazaki K, Saito K, Yamada A, Han X, Funada K, Fukumoto E, Haruyama N, Iwamoto T, Takahashi I, Fukumoto S.
  • Journal Title: Sci Rep. Volume: 27 Issue: 1 Pages: 45181-45181
  • DOI: 10.1038/srep45181
  • NAID: 120006534986
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinicostatistical analysis of congenitally missing permanent teeth in Japanese patients with cleft lip and/or palate. (2016)
  • Author(s): Sato M, Baba Y, Haruyama N, Higashihori N, Tsuji M, Suzuki S, Moriyama K.
  • Journal Title: Orthodontic Waves. Volume: 75 Issue: 2 Pages: 41-45
  • DOI: 10.1016/j.odw.2016.06.001
  • Peer Reviewed
• [Journal Article] 口唇裂口蓋裂患者の矯正歯科受診と咬合の実態 -九州大学病院矯正歯科における43年間の臨床統計－ (2016)
  • Author(s): 祐田京子, 丸山和宏, 鈴木陽, 安永敦, 下村卓弘, 吉崎恵悟, 春山直人, 高橋一郎
  • Journal Title: 日本口蓋裂学会雑誌 Volume: 41 Pages: 192-200
  • NAID: 130005281889
  • Peer Reviewed
• [Journal Article] Plakophilin-1, a novel Wnt signaling regulator, is critical for tooth development and ameloblast differentiation (2016)
  • Author(s): Miyazaki K, Yoshizaki K, Arai C, Yamada A, Saito K, Ishikawa M, Xue H, Funada K, Haruyama N, Yamada Y, Fukumoto S, Takahashi I
  • Journal Title: Plos One Volume: 11 Issue: 3 Pages: 0152206-0152206
  • DOI: 10.1371/journal.pone.0152206
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between length variations in Ser/Asp-rich repeats in phosphophoryn and in vitro precipitation of calcium phosphate. (2015)
  • Author(s): Kobuke S, Suzuki S, Hoshino H, Haruyama N, Nishimura F, Shiba H.
  • Journal Title: Arch Oral Biol Volume: 60 Issue: 9 Pages: 1263-72
  • DOI: 10.1016/j.archoralbio.2015.05.013
  • Peer Reviewed / Open Access
• [Presentation] Stim1はマウスのエナメル質の石灰化およびエナメル芽細胞成熟期にみられる周期性を制御する (2017)
  • Author(s): 古川雄亮, 春山直人, 二階堂まりこ, 中西正光, 笠 法子, 大洞將嗣, 呉本晃一, 吉崎恵悟, 高橋一郎.
  • Organizer: 第12回九州矯正歯科学会学術大会
  • Place of Presentation: 宮崎
  • Year and Date: 2017-03-18
• [Presentation] ストア作動性Ca2+流入の異常による外胚葉異形成症におけるエナメル質形成不全の発症メカニズム. (2016)
  • Author(s): 古川雄亮, 春山直人, 二階堂まりこ, 中西正光, 笠 法子, 大洞將嗣, 呉本晃一, 吉崎恵悟, 高橋一郎
  • Organizer: 第75回 日本矯正歯科学会大会
  • Place of Presentation: 徳島
  • Year and Date: 2016-11-07