Effects of masticatory function on extracellular matrix expression and mechanical property of the TMJ disc

• Project/Area Number: 18K09862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Tohoku University
• Principal Investigator: Mizoguchi Itaru 東北大学, 歯学研究科, 教授 (20200032)
• Co-Investigator(Kenkyū-buntansha): 飯嶋 雅弘 北海道医療大学, 歯学部, 教授 (20305915) ; 鳥谷 奈保子 北海道医療大学, 歯学部, 助教 (20433435) ; 岡山 三紀 北海道医療大学, 歯学部, 講師 (30382500) ; 荒川 俊哉 北海道医療大学, 歯学部, 教授 (40306254)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 関節円板 / 細胞外基質 / コラーゲン / 咀嚼機能 / 関節荷重 / プロテオグリカン / 軟食摂取 / 細胞外マトリックス / mRNA発現 / 免疫組織化学 / 機械的特性

Outline of Final Research Achievements

The expression and assembly of the extracellular matrix are profoundly associated with mechanical properties and pathological responses of the temporomandibular joint (TMJ). To understand the adaptive responses and pathological processes of the TMJ disc to joint loading, we examined the expression of proteoglycans and collagens at the mRNA levels in rat TMJ discs in response to altered joint loading caused by anterior bite plane and soft diet. Biochemical and quantitative real-time RT-PCR indicated that GAG content and versican, biglycan and decorin mRNA levels increased in the bite plane groups. GAG content and all proteoglycan and collagen expression levels decreased significantly in the soft-diet group. These results indicate that joint loading influences proteoglycan and collagen mRNA expression in the TMJ disc, which has important biological significance for adaptation to complicated biomechanical requirements and for tissue maintenance in the TMJ disc.

Academic Significance and Societal Importance of the Research Achievements

近年，顎関節症患者の増加とその若年化傾向が歯科学全体での大きな問題となってきており，その原因の究明が求められているが，現在までのところ，顎関節症の発症に関する正確なメカニズムは不明である．本研究では、関節に加わる荷重の増減あるいは咀嚼機能の変化が顎関節の機械的特性に関わる細胞外基質の形成に大きな影響を及ぼすことが明らかになった．本研究で得られた研究成果は，学術的意義が高いだけでなく、顎関節症の発症メカニズム解明ひいては顎関節症の治療の一助になるものと考えられる．

Research Products

• [Journal Article] The miR-155-5p inhibits osteoclast differentiation through targeting CXCR2 in orthodontic root resorption (2021)
  • Author(s): Jiang H, Kitaura H, Liu L, Mizoguchi I, Liu S.
  • Journal Title: J Periodontal Res Volume: - Issue: 4 Pages: 761-773
  • DOI: 10.1111/jre.12875
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation (2021)
  • Author(s): Hasegawa Tatsuya、Venkata Suresh V.、Yahata Yoshio、Nakano Masato、Suzuki Shigeto、Suzuki Shigeki、Yamada Satoru、Kitaura Hideki、Mizoguchi Itaru、Noiri Yuichiro、Handa Keisuke、Saito Masahiro
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 2613-2613
  • DOI: 10.1038/s41598-021-82167-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of bioactive glass coating by electrophoretic deposition on esthetical, bending, and frictional performance of orthodontic stainless steel wire (2020)
  • Author(s): Kawaguchi K, Iijima M, Muguruma T, Endo K, Mizoguchi I
  • Journal Title: Dental Materials Journal Volume: 39 Issue: 4 Pages: 593-600
  • DOI: 10.4012/dmj.2019-085
  • NAID: 130007884193
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2020-07-30
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TNF-α stimulates the expression of RANK during orthodontic tooth movement (2020)
  • Author(s): Noguchi Takahiro、Kitaura Hideki、Ogawa Saika、Qi Jiawei、Shen Wei-Ren、Ohori Fumitoshi、Marahleh Aseel、Nara Yasuhiko、Pramusita Adya、Mizoguchi Itaru
  • Journal Title: Archives of Oral Biology Volume: 117 Pages: 104796-104796
  • DOI: 10.1016/j.archoralbio.2020.104796
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice (2020)
  • Author(s): Nara Yasuhiko、Kitaura Hideki、Ogawa Saika、Shen Wei-Ren、Qi Jiawei、Ohori Fumitoshi、Noguchi Takahiro、Marahleh Aseel、Pramusita Adya、Kinjo Ria、Mizoguchi Itaru
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 17 Pages: 6120-6120
  • DOI: 10.3390/ijms21176120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption (2020)
  • Author(s): Kitaura Hideki、Marahleh Aseel、Ohori Fumitoshi、Noguchi Takahiro、Shen Wei-Ren、Qi Jiawei、Nara Yasuhiko、Pramusita Adya、Kinjo Ria、Mizoguchi Itaru
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 14 Pages: 5169-5169
  • DOI: 10.3390/ijms21145169
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption (2020)
  • Author(s): Qi Jiawei、Kitaura Hideki、Shen Wei-Ren、Ogawa Saika、Ohori Fumitoshi、Noguchi Takahiro、Marahleh Aseel、Nara Yasuhiko、Adya Pramusita、Mizoguchi Itaru
  • Journal Title: BioMed Research International Volume: 2020 Pages: 1-9
  • DOI: 10.1155/2020/7189084
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice (2020)
  • Author(s): Shen Wei-Ren、Kitaura Hideki、Qi Jiawei、Ogawa Saika、Ohori Fumitoshi、Noguchi Takahiro、Marahleh Aseel、Nara Yasuhiko、Adya Pramusita、Mizoguchi Itaru
  • Journal Title: The Angle Orthodontist Volume: 91 Issue: 1 Pages: 111-118
  • DOI: 10.2319/021320-103.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Obtaining Primary Osteocytes through Murine Calvarial Fractionation of GFP-Expressing Osteocytes (2020)
  • Author(s): Marahleh Aseel、Kitaura Hideki、Ogawa Saika、Shen Wei-Ren、Qi Jiawei、Ohori Fumitoshi、Noguchi Takahiro、Nara Yasuhiko、Pramusita Adya、Kinjo Ria、Mizoguchi Itaru
  • Journal Title: Journal of Visualized Experiments Volume: 160 Issue: 160
  • DOI: 10.3791/61513
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sugar Metabolism of Scardovia wiggsiae, a Novel Caries-Associated Bacterium (2020)
  • Author(s): Kameda M, Abiko Y, Washio J, Anne C. R. Tanner, Christine A. Kressirer, Mizoguchi I, Takahashi N
  • Journal Title: Frontiers in Microbiology Volume: 25 Pages: 479-479
  • DOI: 10.3389/fmicb.2020.00479
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of TNF-α-induced sclerostin on osteocytes during orthodontic tooth movement (2020)
  • Author(s): Ohori F, Kitaura H, Ogawa S, Shen WR, Qi J, Noguchi T, Marahleh A, Nara Y, Pramusita A, Mizoguchi I.
  • Journal Title: J Immunol Res Volume: 2019 Pages: 1-10
  • DOI: 10.1155/2019/9716758
  • Peer Reviewed / Open Access
• [Journal Article] Effects of pastes containing ion-releasing particles on dentin remineralization (2019)
  • Author(s): IIJIMA Masahiro、ISHIKAWA Rina、KAWAGUCHI Kyotaro、ITO Shuichi、SAITO Takashi、MIZOGUCHI Itaru
  • Journal Title: Dental Materials Journal Volume: 38 Issue: 2 Pages: 271-277
  • DOI: 10.4012/dmj.2018-015
  • NAID: 130007628891
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2019-03-28
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of an orthodontic retention mouse model and the effect of anti-c-Fms antibody on orthodontic relapse (2019)
  • Author(s): Qi J, Kitaura H, Shen WR, Kishikawa A, Ogawa S, Ohori F, Noguchi T, Marahleh A, Nara Y, Mizoguchi I.
  • Journal Title: PLos One Volume: 14 Issue: 6 Pages: e0214260-e0214260
  • DOI: 10.1371/journal.pone.0214260
  • Peer Reviewed / Open Access
• [Journal Article] TNF-α is responsible for the contribution of stromal cells to osteoclast and odontoclast formation during orthodontic tooth movement (2019)
  • Author(s): Ogawa S, Kitaura H, Kishikawa A, Qi J, Shen WR, Ohori F, Noguchi T, Marahleh A, Nara Y, Ochi Y, Mizoguchi I.
  • Journal Title: PLos One Volume: 14 Issue: 10 Pages: e0223989-e0223989
  • DOI: 10.1371/journal.pone.0223989
  • Peer Reviewed / Open Access
• [Journal Article] TNF-α directly enhances osteocyte RANKL expression and promotes osteoclast formation. (2019)
  • Author(s): Marahleh A, Kitaura H, Ohori F, Kishikawa A, Ogawa S, Shen WR, Qi J, Noguchi T, Nara Y, Mizoguchi I.
  • Journal Title: Front Immunol Volume: 10 Issue: 3 Pages: 2925-2925
  • DOI: 10.3390/ijms21031130
  • Peer Reviewed / Open Access
• [Journal Article] Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivoThrough GPR120 by Inhibiting TNF-α Production in Macrophages and Directly Inhibiting Osteoclast Formation (2019)
  • Author(s): Akiko Kishikawa, Hideki Kitaura, Keisuke Kimura, Saika Ogawa, Jiawei Qi, Wei-Ren Shen, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Atsuhiko Ichimura, Itaru Mizoguchi
  • Journal Title: frontier in endocrinology Volume: Volume 10 Pages: 157-157
  • DOI: 10.3389/fendo.2019.00157
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro (2019)
  • Author(s): Marahleh A, Kitaura H, Ishida M, Shima K, Kishikawa A, Ogawa S, Shen WR, Qi J, Ohori F, Noguchi T, Nara Y, Mizoguchi I
  • Journal Title: J Vis Exp Volume: 18 Issue: 145 Pages: 145-145
  • DOI: 10.3791/59089
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accuracy of digital models generated by conventional impression/plaster-model methods and intraoral scanning (2018)
  • Author(s): Tomita Y, Uechi J, Konno M, Sasamoto S, Iijima M, Mizoguchi I
  • Journal Title: Dental Materials Journal Volume: 37 Issue: 4 Pages: 628-633
  • DOI: 10.4012/dmj.2017-208
  • NAID: 130007420981
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2018-07-26
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Inhibitory Effect of IL-33 on TNF-α-Induced Osteoclastogenesis and Orthodontic Tooth Movement. (2020)
  • Author(s): Ohori F, Kitaura H, Ogawa S, Noguchi T, Marahleh A, Nara Y, Pramusita A, Kinjo R, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Diabetes Medicine Glucagon-Like Peptode-1 Receptor Agonist Inhibits Orthodontic Tooth Movement and Root Resorption. (2020)
  • Author(s): Ohori F, Kitaura H, Shen WR, Ogawa S, Noguchi T, Marahleh A, Nara Y, Pramusita A, Kinjo R, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Diabetes medicine DPP-4 inhibitor inhibits orthodontic tooth movement and associated root resorption in mouse tooth movement model. (2020)
  • Author(s): Noguchi T, Kitaura H, Qi J, Ogawa S, Ohori F, Marahleh A, Nara Y, Pramusita A, Kinjo R, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] TNF-α stimulates the expression of RANK during orthodontic tooth movement. (2020)
  • Author(s): Noguchi T, Kitaura H, Ogawa S, Ohori F, Marahleh A, Nara Y, Pramusita A, Kinjo R, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Role of TNF-α-responsible stromal clls to osteoclast and odontoclast formation during orthodontic tooth movement. (2020)
  • Author(s): Ogawa S, Kitaura H, Ohori F, Noguchi T, Marahleh A, Nara Y, Pramusita A, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Statistical and clinical survey of congenital disease patients in the past 10-year period in Tohoku University Hospital Department of orthodontics. (2020)
  • Author(s): Sasaki S, Kitaura H, Maeda T, Ogawa S, Ogura H, Kameda M, Kinjo R, Shigemi S, Numazaki K, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Craniofacial characteristics, malocclusions and successful orthodontic treatment results in 3 Diamond Blackfan Syndrome patients. (2020)
  • Author(s): Sasaki S, Kitaura H, Yoshida M, Mayama A, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Micro-osteoperforations induce TNF-α expression and accelerate orthodontic tooth movement in mice. (2020)
  • Author(s): Kinjo R, Kitaura H, Ogawa S, Ohori F, Noguchi T, Marahleh A, Nara Y, Pramusita A, Mizoguchi I.
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Solt-sensitive hypertension exacerbates osteoclastogenesis and bone resorption in vivo. (2020)
  • Author(s): Pramusita A, Kitaura H, Ogawa S, Ohori F, Noguchi T, Marahleh A, Nara Y, Kinjo R, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] TNF-α induces orthodontic tooth movement and enhances osteocyte RANKL expression by activating MAPKs and NFκB pathway. (2020)
  • Author(s): Marahleh A, Kitaura H, Ohori F, Ogawa S, Noguchi T, Nara Y, Pramusita A, Kinjo R, Mizoguchi I.
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Facial asymmetry and unilateral condylar hyperplasia treated with ipsilateral condylectomy and orthodontic treatment. (2020)
  • Author(s): Kishikawa A, Fukunaga T, Nogami S, Seiryu M, Shigemi S, Kumamoto H, Takahashi T, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Three-dimensional evaluation of temporomandibular joint cavity in three cases with severe skeletal asymmetry and occlusal cant. (2020)
  • Author(s): Oyanagi T, Maeda T, Yoshizawa M, Kimura S, Mayama A, Seiryu M, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Treatment of open bite and unilateral scissors bite with orthodontic anchor screws in a middle-age (2020)
  • Author(s): Oyanagi T, Yoshida M, Mayama A, Masahiro Seiryu M, Itaru Mizoguchi
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] Five-year clinical investigation of orthodontic anchow screw used for surgical orthodontic treatment (2020)
  • Author(s): Sasaki S, Mayama A, Oyangi T, Ito A, Ogura H, Seiryu M, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] 3D evaluation of changes in the alveolar bone due to upper anterior teeth retraction with orthodontic anchor screws. (2020)
  • Author(s): Ito A, Mayama A, Oyanagi T, Sasaki S, Ogura H, Seiryu M, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] 3D cast analysis of 10 years retention case treated with miniscrews for distalization of maxillary molar. (2020)
  • Author(s): Irie D, Oyanagi T, Ito-Okubo M, Mayama A, Seiryu M, Mizoguchi I
  • Organizer: The 9th International Orthodontic Congress
  • Int'l Joint Research
• [Presentation] TNF- α increases sclerostin expression in osteocytes during orthodontic tooth movement (2019)
  • Author(s): Ohori F, Kitaura H, Marahleh A, Kishikawa A, Ogawa S, Qi J, Shen WR, Noguchi T, Nara Y, Mizoguchi I.
  • Organizer: Annual Meeting of International Association of Dental Research （国際学会）
  • Int'l Joint Research
• [Presentation] TNF- α directly enhances osteocytes RANKL expression and promotes osteoclast formation (2019)
  • Author(s): Marahleh A, Kitaura H, Ohori F, Kishikawa A, Ogawa S, Qi J, Shen WR, Noguchi T, Nara Y, Mizoguchi I.
  • Organizer: American Society for Bone and Mineral Research Annual Meeting（国際学会）
  • Int'l Joint Research
• [Presentation] TNF- α is responsible for stromal cell contribution to osteoclast and odontoclast formation during orthodontic tooth movement (2019)
  • Author(s): Ogawa S, Kitaura H, Marahleh A, Kishikawa A, Qi J, Shen WR, Ohori F, Noguchi T, Nara Y, Mizoguchi I.
  • Organizer: American Society for Bone and Mineral Research Annual Meeting（国際学会）
  • Int'l Joint Research
• [Presentation] 下顎骨の成長と下顎頭軟骨の生物学的特徴 (2019)
  • Author(s): 溝口 到
  • Organizer: 東北矯正歯科学会秋季セミナー
  • Invited
• [Presentation] 下顎骨の成長と下顎頭軟骨の生物学的特徴 (2019)
  • Author(s): 溝口 到
  • Organizer: 北海道矯正歯科学会
  • Invited
• [Presentation] 下顎前歯部叢生の後戻を考える (2018)
  • Author(s): 溝口 到
  • Organizer: 日本成人矯正歯科学会
  • Invited
• [Presentation] 関節荷重が成長期ラット下顎頭軟骨の細胞外基質mRNA発現に及ぼす影響 (2018)
  • Author(s): 山口 優、樫尾治奈、中尾友也、溝口 到
  • Organizer: 日本矯正歯科学会
• [Presentation] DCLコーティングを施した矯正用ワイヤーの曲げ特性と摩擦特性における水素含有量の影響 (2018)
  • Author(s): 六車武史、飯嶋雅弘、河口馨太朗、溝口 到
  • Organizer: 日本矯正歯科学会
• [Presentation] 異なる垂直的顎顔面形態を有する混合歯列期Ⅱ級症例におけるcervical headgearの治療効果 (2018)
  • Author(s): 山崎敦永、鳥谷奈保子、林 明里、溝口 到
  • Organizer: 日本矯正歯科学会
• [Remarks] 東北大学大学院歯学研究科 顎口腔矯正学分野
  • URL: http://www.orthod.dent.tohoku.ac.jp/index.html