Wntシグナルを介した重度歯根吸収発生機構の解明と進行抑制への基礎的検討

• Project/Area Number: 16K11795
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Nihon University
• Principal Investigator: 山口 大 日本大学, 松戸歯学部, 准教授 (60333100)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Discontinued (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 歯根吸収 / 歯根膜 / Wntシグナル / 歯の移動 / Wnt5a

Outline of Annual Research Achievements

研究の目的は、歯根膜線維芽細胞と破歯前駆細胞におけるシグナル伝達、特にWntシグナルに焦点を当て、矯正治療による歯根吸収発生メカニズムを解明するとともに、その抑制方法を検討することである。具体的には、ラットの実験的歯の移動において人為的に歯根吸収を惹起させ、歯根吸収部の歯根膜線維芽細胞と破歯前駆細胞におけるWnt5a発現、およびRANK/RANKL発現について検討した。In vitroでは歯根膜細胞圧迫モデルにて過大な荷重を加え、Wnt5aとRANKLの発現を検討した。
In vivoにおいて1週目ではHF群で歯根吸収が認められた。さらに、歯根吸収部でWnt5a,、RANKL、 IL-6、 IL-17の陽性細胞の増加が認められた。 さらに、カスパーゼ3および8陽性細胞は, 3日目および5日目に50 g群のセメント質表層で増加した。TRAP, RANKL陽性細胞数およびカスパーゼ3, 8陽性細胞率は, 10 g群と比較し50 g群で有意な増加が認められた。In vitroではヒト歯根膜線維芽細胞に4.0g/cm2と1.0g/cm2の持続的圧迫力を加えた時、Wnt5aの遺伝子発現は12時間でピークに達し、1.0g/cm2の加重を加えた時に比べて、4.0g/cm2の加重を加えた時の方が減少した。RANKL、IL-6の遺伝子発現は12時間でピークに達し、1.0g/cm2の加重を加えた時に比べて、4.0g/cm2の加重を加えた時の方が増大した。
以上のことから、歯根吸収の発現にWntシグナルが関与していることが示唆された。

Research Products

• [Journal Article] Micro-osteoperforations accelerate orthodontic tooth movement by stimulating periodontal ligament cell cycles. (2018)
  • Author(s): Sugimori T, Yamaguchi M, Shimizu M, Kikuta J, Hikida T, Hikida M, Murakami Y, Kasai K..
  • Journal Title: Am J Orthod Dentofacial Orthop Volume: －
  • Peer Reviewed / Open Access
• [Journal Article] Effect of caspases and RANKL induced by heavy force in orthodontic root resorption. (2018)
  • Author(s): Minato Y, Yamaguchi M, Shimizu M, Kikuta J, Hikida T, Hikida M, Suemitsu M, Kuyama K, Kasai K..
  • Journal Title: Korean Journal of Orthodontics Volume: ー
  • Peer Reviewed / Open Access
• [Journal Article] Effects of daidzein on the production of type I collagen and matrix metalloproteinase1 by stretched human periodontal ligament cells. (2018)
  • Author(s): Yamaguchi M, Nakayama E, Shimizu M, Kikuta J, Horihata S, Kasai K..
  • Journal Title: International Journal of Oral- Medical Sciences. Volume: ー
  • NAID: 130007403289
  • Peer Reviewed / Open Access
• [Journal Article] Daidzein inhibits relapse after rat experimental tooth movement. (2018)
  • Author(s): Nakayama E, Yamaguchi M, Kikuta J, Shimizu M, Hikida T, Hikida M, Murakami Y, Suemitu M, Kuyama K, Kasai K..
  • Journal Title: International Journal of Oral- Medical Sciences. Volume: ー
  • NAID: 130007403287
  • Peer Reviewed / Open Access
• [Journal Article] Micro-osteoperforations accelerate orthodontic tooth movement by stimulating periodontal ligament cell cycles. (2018)
  • Author(s): Sugimori T, Yamaguchi M, Shimizu M, Kikuta J, Hikida T, Hikida M, Murakami Y, Kasai K.
  • Journal Title: Am J Orthod Dentofacial Orthop Volume: ー
  • Peer Reviewed / Open Access
• [Journal Article] Effect of caspases and RANKL induced by heavy force in orthodontic root resorption. (2018)
  • Author(s): Minato Y, Yamaguchi M, Shimizu M, Kikuta J, Hikida T, Hikida M, Suemitsu, M Kuyama K, Kasai K..
  • Journal Title: Korean Journal of Orthodontics Volume: ー
  • Peer Reviewed / Open Access
• [Journal Article] Effects of daidzein on the production of type I collagen and matrix metalloproteinase1 by stretched human periodontal ligament cells.. (2018)
  • Author(s): Yamaguchi M, Nakayama E, Shimizu M, Kikuta J, Horihata S, Kasai.K.
  • Journal Title: International Journal of Oral- Medical Sciences. Volume: ー
  • NAID: 130007403289
  • Peer Reviewed / Open Access
• [Journal Article] Daidzein inhibits relapse after rat experimental tooth movement. (2018)
  • Author(s): Nakayama E, Yamaguchi M, Kikuta J, Shimizu M, Takuji Hikida T, Hikida M, Murakami Y, Suemitu M, Kuyama K, Kasai.K.
  • Journal Title: International Journal of Oral- Medical Sciences. Volume: ー
  • NAID: 130007403287
  • Peer Reviewed / Open Access
• [Journal Article] <b>Caspase-mediated Apoptosis by Compressive Force Induces RANKL in Cementoblasts </b> (2018)
  • Author(s): Yamaguchi M, Minato, Y Shimizu M, Kikuta J, Hikida T, Kasai. K.
  • Journal Title: International Journal of Oral-Medical Sciences Volume: 16 Issue: 2 Pages: 31-38
  • DOI: 10.5466/ijoms.16.31
  • NAID: 130006320938
  • ISSN: 1347-9733, 2185-4254
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between root resorption and individual variation in the calcium/phosphorous ratio of cementum. (2017)
  • Author(s): Yao-Umezawa E, Yamaguchi M, Shimizu M, Kikuta J, Suzuki K, Kasai K.
  • Journal Title: Am J Orthod Dentofacial Orthop, Volume: 152 Issue: 4 Pages: 465-470
  • DOI: 10.1016/j.ajodo.2016.12.029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] <b>Expression of IL-34 in Root Resorption by Excessive Orthodontic Force </b> (2017)
  • Author(s): Kohno R, Yamaguchi M, Hikida T, Kikuta J, Shimizu M, Takahashi-Hikida M, Murakami Y, Kasai K.
  • Journal Title: International Journal of Oral-Medical Sciences Volume: 16 Issue: 1 Pages: 8-15
  • DOI: 10.5466/ijoms.16.8
  • NAID: 130006894958
  • ISSN: 1347-9733, 2185-4254
  • Peer Reviewed / Open Access
• [Journal Article] ラットの実験的歯の移動においてジグリングはIL-17を介して歯根吸収を重篤化する. (2017)
  • Author(s): 石川 友子，山口 大, 疋田 拓史，菊田 純，清水 真美，高橋 桃子，村上 嘉規，葛西 一貴.
  • Journal Title: 日大口腔科学 Volume: 43. Pages: 83-91
  • NAID: 40021289677
  • Peer Reviewed / Open Access
• [Journal Article] An energy dispersive x-ray microanalysis study in root apex of human cementum. (2017)
  • Author(s): Yao-Umezawa E, Yamaguchi M, Shimizu M, Kikuta J, Suzuki K, Kasai K.
  • Journal Title: Am J Orthod Dentofacial Orthop Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Individual Variations in the Hardness and Elastic Modulus of the Human Cementum (2016)
  • Author(s): Yamaguchi M, Yao-Umezawa E, Tanimoto Y, Shimizu M, Kikuta J, Hikida T, Takahashi-Hikida M, Horihata S, Suzuki K, Kasai K.
  • Journal Title: Journal of Hard Tissue Biology Volume: 25 Issue: 4 Pages: 345-350
  • DOI: 10.2485/jhtb.25.345
  • NAID: 130005249139
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Jiggling Force Aggravates Orthodontic Root Resorption Via TNF-α during Rat Experimental Tooth Movement (2016)
  • Author(s): Ohashi M, Yamaguchi M, Hikida T, Kikuta J, Shimizu M, Goseki T, Kasai K.
  • Journal Title: International Journal of Oral-Medical Sciences Volume: 14 Issue: 4 Pages: 82-90
  • DOI: 10.5466/ijoms.14.82
  • NAID: 130005142171
  • ISSN: 1347-9733, 2185-4254
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of orthodontic root resorption under heavy and jiggling forces during experimental tooth movement. (2016)
  • Author(s): Hikida T, Yamaguchi M, Shimizu M, Kikuta J, Yoshino T, Kasai K.
  • Journal Title: Korean J Orthod Volume: 46(4) Issue: 4 Pages: 228-241
  • DOI: 10.4041/kjod.2016.46.4.228
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Micro-osteoperforationsによるラット歯根膜のGeneChip遺伝子発現プロファイリング (2016)
  • Author(s): 山口大, 杉森匡，今村隆一，葛西一貴
  • Journal Title: 成人矯正歯科学会雑誌 Volume: 23 Pages: 2-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Daidzein inhibits relapse after experimental tooth movement (2017)
  • Author(s): Erika Nakayama, Masaru Yamaguch,Jun Kikuta, Takuji Hikida, Momoko hikida,Kazutaka Kasai
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Relationship between root resorption and apoptosis in cementum. (2017)
  • Author(s): Yukari Minato, Masaru Yamaguchi, Mami Shimizu, Jun Kikuta, Takuji Hikida, Momoko Hikida,Masaaki Suemitsu, Kayo Kuyama, Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Jiggling force aggregates root resorption via production of inflammatory cytokines. (2017)
  • Author(s): Takuji Hikida., Masaru Yamaguchi., Mami Shimizu., Jun Kikuta., Momoko Hikida., Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Notch signaling aggravates root resorption by suppressing Wnt signaling. (2017)
  • Author(s): Jun Kikuta, Masaru Yamaguchi, Mami Shimizu, Takuji Hikida, Momoko Hikida, Takehiro Iwane,Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Hypoxia induced by nasal obstraction natural killer cell activity. (2017)
  • Author(s): Tomonori Sato, Masaru Yamaguchi,Yoshiki Murakami, Ryoki Kobayashi, Sinichi Negishi, Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Hardness and Ca/P ratio of cementum involve in root resorption. (2017)
  • Author(s): Eriko Umezawa-Yao, Masaru Yamaguchi, Mami ShimizJun Kikuta, Kunihiro Suzuki,Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] The utility of GFRP orthodontic wire for clinical application (2017)
  • Author(s): Naomi Minami, Masaru Yamaguchi, Yasuhiro Tanimoto, Kiyoshi Arai, Masaaki Suemitsu, Kayo Kuyama, Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Effect of nasal obstruction on the immune system (2017)
  • Author(s): Yoshiki Murakami, Masaru Yamaguchi, Mami Shimizu, Jun Kikuta, Tomonori Sato, Yurie Horigome, Ryoki Kobayashi ,Kazutaka,Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USASan Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Micro-osteoperforations accelerate orthodontic tooth movement by activating PDL cell cycles (2017)
  • Author(s): Tadasu Sugimori, Masaru Yamaguchi, Mami Shimizu, Jun Kikuta, Takuji Hikida, Momoko Takahashi, Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Basic study of an orthodontic anchor screw using bioabsorble materials (2017)
  • Author(s): Masaru Yamaguchi, Momoko Takahashi, Yasuhiro Tanimoto, Eriko Umezawa-Yao, Kazutaka Kasai
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Compression Force Induces Wnt Signaling in Periodontal Ligament Cells (2017)
  • Author(s): Hitomi Saito, Masaru Yamaguchi, Mami Shimizu, Jun Kikuta, Yoshiki Murakami, Kazutaka Kasai.
  • Organizer: 95th International Association for Dental Research
  • Place of Presentation: San Francisco, Calif., USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Analysis of microbial profile to failure of orthodontic anchor screw. (2017)
  • Author(s): Masaru Yamaguchi
  • Organizer: 9th World implant Orthodontic Conference.
  • Int'l Joint Research / Invited
• [Presentation] 成長期ラットの鼻閉塞改善後における顎顔面領域の骨成長変化. (2017)
  • Author(s): 佐藤友紀，山口大，村上嘉規，小林良喜，根岸慎一，葛西一貴．
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] Micro-osteoperforationsは歯槽骨の骨密度の減少を介して歯の移動速度を促進させる. (2017)
  • Author(s): 杉森匡, 山口 大, 清水真美, 菊田 純, 疋田拓史, 疋田桃子, 村上嘉規, 葛西一貴.
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] メカ二カルストレスによる歯根膜のWntシグナル発現が、歯根吸収を増悪する. (2017)
  • Author(s): 齊籐瞳, 山口 大, 菊田 純, 疋田拓史, 疋田桃子, 清水真美, 村上嘉規, 葛西一貴.
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 圧迫力負荷によるセメント芽細胞のアポトーシスと歯根吸収の関係性. (2017)
  • Author(s): 湊友香里, 山口 大, 清水真美、菊田純、疋田拓史、疋田桃子、村上嘉規、葛西一貴.
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] Daidzeinはコラーゲン代謝を活性化し後戻りを抑制する. (2017)
  • Author(s): 中山瑛加、山口 大、疋田拓史、清水真美、菊田純、村上嘉規、疋田桃子、葛西一貴.
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] ヒト歯根膜線維芽細胞の持続的圧迫力に対するNotchシグナルとWntシグナルの相互関係. (2017)
  • Author(s): 岩根健大、山口 大、菊田純、疋田拓史、疋田桃子、清水真美、村上嘉規、葛西一貴.
  • Organizer: 第76回日本矯正歯科学会大会
• [Presentation] 歯の移動による歯根吸収とセメント細胞のアポトーシスの関与 (2016)
  • Author(s): 湊友香里、山口大、清水真美、菊田純、高橋桃子、吉野智一、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] 歯の移動速度は皮質骨切除術により歯根膜細胞周期の活性化を介して促進する (2016)
  • Author(s): 杉森匡、山口大、清水真美、菊田純、疋田拓史、高橋桃子、村上嘉規、吉野智一、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] 根尖部セメント質の物性および化学組成が歯根吸収の発生に及ぼす影響 (2016)
  • Author(s): 梅澤恵梨子、山口大、清水真美、吉野智一、菊田純、鈴木久仁博、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] GFRP矯正ワイヤーのin vivoによる歯の移動量の検討 (2016)
  • Author(s): 南奈緒美、谷本安浩、荒井清、山口大、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] 歯の移動後のdaidzeinの後戻り抑制効果の検討 (2016)
  • Author(s): 中山瑛加、山口大、高橋桃子、疋田拓史、清水真美、菊田純、村上嘉規、吉野智一、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] 軽度低酸素状態がラットNK細胞活性に及ぼす影響 (2016)
  • Author(s): 佐藤友紀、山口大、村上嘉規、小林良喜、根岸慎一、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] 持続的圧迫力がヒト歯根膜線維芽細胞のWnt5a発現に及ぼす影響について (2016)
  • Author(s): 斉藤瞳、山口大、菊田純、疋田拓史、高橋桃子、清水真美、村上嘉規、吉野智一、葛西一貴
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: 徳島市アスティとくしま, 徳島県, 徳島市
  • Year and Date: 2016-11-07
• [Presentation] Jiggling force aggravates orthodontic root resorption via TNF-α during rat experimental tooth movement. (2016)
  • Author(s): Yamaguchi M, Hikida T, Yoshino T, Kikuta J, Shimizu M, Takahashi M, Kasai K.
  • Organizer: 38th Asia Pacific Dental Congress. .
  • Place of Presentation: Hong Kong, China.
  • Year and Date: 2016-06-17
  • Int'l Joint Research