Evaluation of the effects of occlusal disharmony-induced stress on bone metabolism during growth period in mice

• Project/Area Number: 26861771
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Shimizu Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (60631968)
• Co-Investigator(Renkei-kenkyūsha): Aoki Kazuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40272603)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 咬合異常 / グルココルチコイド / 骨形態計測 / ストレスホルモン

Outline of Final Research Achievements

The purpose of this study was to investigate whether occlusal disharmony-induced stress decreases bone mass. Five-week-old C57BL/6J male mice were used. A 0.5-mm increase in the vertical height of occlusion was used to induce occlusal disharmony for a period of 7 days. Serum corticosterone levels were significantly higher on post-induction day 7, with radiological evidence of osteopenia of long bones of the hind limbs. Osteopenia was associated with a reduction of the mechanical properties of the tibia and femur, with a significant suppression of bone formation parameters as evaluated by bone histomorphometric analysis of the tibial metaphysis. Our findings at the level of bones were supported by our assessment of serum markers of systemic metabolism. Therefore, occlusal disharmony-induced stress may lead to osteopenia and reduce the mechanical strength of the bone through an increase in serum glucocorticoid levels in mice.

Research Products

• [Journal Article] Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model. (2016)
  • Author(s): Arai Y, Aoki K, Shimizu Y, Tabata Y, Ono T, Murali R, Mise-Omata S, Wakabayashi N
  • Journal Title: Eur J Pharmacol Volume: 782 Pages: 89-97
  • DOI: 10.1016/j.ejphar.2016.04.049
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intermittent Hypoxia Influences Alveolar Bone Proper Microstructure via Hypoxia-Inducible Factor and VEGF Expression in Periodontal Ligaments of Growing Rats. (2016)
  • Author(s): Shuji Oishi, Yasuhiro Shimizu, Jun Hosomichi, Yoichiro Kuma, Hideyuki Maeda, Hisashi Nagai, Risa Usumi-Fujita, Sawa Kaneko, Naoki Shibutani, Jun-ichi Suzuki, Ken-ichi Yoshida, Takashi Ono
  • Journal Title: Front. Physiol. Volume: 16 Pages: 416-416
  • DOI: 10.3389/fphys.2016.00416
  • Peer Reviewed / Open Access
• [Journal Article] Intermittent hypoxia causes mandibular growth retardation and macroglossia in growing rats. (2016)
  • Author(s): Hosomichi J, Kuma YI, Oishi S, Nagai H, Maeda H, Usumi-Fujita R, Shimizu Y, Kaneko S, Shitano C, Suzuki JI, Yoshida KI, Ono T.
  • Journal Title: Am J Orthod Dentofacial Orthop. Volume: 151 Issue: 2 Pages: 363-371
  • DOI: 10.1016/j.ajodo.2016.02.033
  • Peer Reviewed
• [Journal Article] Intermittent hypoxia induces disturbances in craniofacial growth and discrepancies in craniofacial morphology. (2016)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Nagai H, Maeda H, Usumi-Fujita R, Kaneko S, Shitano C, Suzuki J, Yoshida K, Ono T.
  • Journal Title: Archives of Oral Biology Volume: Jan;61 Pages: 115-24
  • DOI: 10.1016/j.archoralbio.2015.10.017
  • Peer Reviewed
• [Journal Article] The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: A bone histomorphometric study. (2015)
  • Author(s): Kato G, Shimizu Y, Arai Y, Suzuki N, Sugamori Y, Maeda M, Takahashi M, Tamura Y, Wakabayashi N, Murali R, Ono T, Ohya K, Mise-Omata S, Aoki K.
  • Journal Title: Arthritis Research & Therapy Volume: Sep 12 Issue: 1 Pages: 251-264
  • DOI: 10.1186/s13075-015-0753-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Micro-computed tomography analysis of changes in the periodontal ligament and alveolar bone proper induced by occlusal hypofunction of rat molars. (2014)
  • Author(s): Yasuhiro Shimizu, Jun Hosomichi, Saeko Nakamura, Takashi Ono.
  • Journal Title: The Korean Journal of Orthodontics Volume: 44(5) Issue: 5 Pages: 263-267
  • DOI: 10.4041/kjod.2014.44.5.263
  • Peer Reviewed
• [Journal Article] Impairment of nasal airway under intermittent hypoxia during growth period in rats. (2014)
  • Author(s): Kuma Y, Usumi-Fujita R, Hosomichi J, Oishi S, Maeda H, Nagai H, Shimizu Y,
  • Journal Title: Arch Oral Biol. Volume: 59 Issue: 11 Pages: 1139-45
  • DOI: 10.1016/j.archoralbio.2014.06.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 咬合異常に伴うストレスは マウス椎骨・長管骨骨密度の低下をもたらす (2016)
  • Author(s): 清水康広、青木和広、加藤玄樹、小野卓史
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティとくしま（徳島県徳島市）
  • Year and Date: 2016-11-07
• [Presentation] 超音波マイクロバブル法を応用した歯周組織への新規NF-κBデコイ導入法の開発 (2016)
  • Author(s): 山口博之、石田雄之、細道純、畑野香澄、笠原由紀、大石修史、隈陽一郎、沖藤明日香、臼見莉沙、清水康広、渋谷直樹、金香佐和、渡邊亮、鈴木淳一、小野卓史
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティとくしま（徳島県徳島市）
  • Year and Date: 2016-11-07
• [Presentation] SDF-1/CXCR4シグナル阻害はラット臼歯の矯正的移動を遅延する (2016)
  • Author(s): 畑野香澄、石田雄之、山口博之、細道純、鈴木淳一、笠原由紀、大石修史、隈陽一郎、沖藤明日香、臼見莉沙、清水康広、渋谷直樹、金香佐和、小野卓史
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティとくしま（徳島県徳島市）
  • Year and Date: 2016-11-07
• [Presentation] Intermittent hypoxia influences bone microstructure via hypoxia inducible factor and VEGF in growing rats (2016)
  • Author(s): Oishi Shuji, Shimizu Yasuhiro, Hosomichi Jun, Kuma Yoichiro, Maeda Hideyuki, Nagai Hisashi, Kaneko Sawa, Ishida Yuji, Shibutani Naoki, Usumi-Fujita Risa, Yamaguchi Hiroyuki, Suzuki Jun-ichi, Yoshida Ken-ichi, Ono Takashi
  • Organizer: 10th Asia Pacific Orthodontics Conference
  • Place of Presentation: Bali (Indonesia)
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] ペプチドが誘導する抜歯後の新生骨形成および歯槽骨保護:BMP-2誘導マウス抜歯窩骨新生モデルによる検証研究 (2016)
  • Author(s): 新井祐貴、青木和広、清水康広、田村幸彦、小野卓史、三瀬節子、Murali Ramachandran、若林則幸
  • Organizer: 第36回日本骨形態計測学会
  • Place of Presentation: 新潟コンベンションセンター（新潟県新潟市）
  • Year and Date: 2016-06-23
• [Presentation] Effect of low-intensity pulsed ultrasound on periodontal tissues in occlusal hypofunctional teeth. (2016)
  • Author(s): Yuki Kasahara, Risa Usumi-Fujita, Jun Hosomichi, Sawa Kaneko, Yuji Ishida, Naoki Shibutani, Yasuhiro Shimizu, Asuka Okito, Shuji Oishi, Yoichiro Kuma, and Takashi Ono.
  • Organizer: The Annual Dental Scientific Conference in Ho chi minh city
  • Place of Presentation: Ho chi minh city (Vietnam)
  • Int'l Joint Research
• [Presentation] 間欠的低酸素暴露は成長期ラット歯槽骨の骨微細構造に影響を与える (2015)
  • Author(s): 大石修史、清水康広、細道純、金香佐和、渋谷直樹、臼見莉沙、舌野知佐、隈陽一郎、中井雄太、鈴木淳一、永井恒志、前田秀将、吉田謙一、小野卓史
  • Organizer: 第74回日本矯正歯科学会学術大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ（福岡市）
  • Year and Date: 2015-11-18
• [Presentation] Intermittent hypoxia triggers inflammatory pathway with down-regulated myofibrillar and mitochondrial biogenesis in the geniohyoid muscle. (2015)
  • Author(s): Jun Hosomichi, Yuta Nakai, Hideyuki Maeda, Yo-ichiro Kuma, Shuji Oishi, Risa Usumi-Fujita, Yasuhiro Shimizu, Sawa Kaneko, Yuji Ishida, Naoki Shibutani, Ken-ichi Yoshida, Takashi Ono
  • Organizer: 第74回日本矯正歯科学会学術大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ（福岡市）
  • Year and Date: 2015-11-18
• [Presentation] Root resorption of maxillary incisors associated with ectopically erupting canines: predisposing factors, diagnosis and prognosis of orthodontic treatment. (2015)
  • Author(s): Matsumoto Y., Hoshomichi J., Ishida Y., Ohmori H., Shimizu Y., Kyuragi T., Shitano C., Kawabe A., Maekawa M., Ikeda Y., Kirii A, Kita S., Sakaguchi T., An J., Yamada K., Suzuki K, Ono T.
  • Organizer: 8th The International Orthodontic Congress
  • Place of Presentation: London (UK)
  • Year and Date: 2015-09-27
  • Int'l Joint Research
• [Presentation] The effects of intermittent hypoxia on the microstructure of growing craniofacial bones. (2015)
  • Author(s): Shuji Oishi, Yasuhiro Shimizu, Jun Hosomichi, Yo-ichiro Kuma, Risa Usumi-Fujita, Hideyuki Maeda, Hisashi Nagai, Chisa Shitano, Sawa Kaneko, Yuji Ishida, Jun-ichi Suzuki, Ken-ichi Yoshida, Takashi Ono
  • Organizer: Sleep 2015
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Intermittent hypoxia induces changes in the expression of the angiogenic factor, nitric oxide synthase 3, with impaired growth of the nasal airway. (2015)
  • Author(s): Yo-ichiro Kuma, Risa Usumi-Fujita, Jun Hosomichi, Shuji Oishi, Yasuhiro Shimizu, Hisashi Nagai, Hideyuki Maeda, Chisa Shitano, Sawa Kaneko, Yuji Ishida, Jun-ichi Suzuki, Ken-ichi Yoshida, Takashi Ono.
  • Organizer: Sleep 2015
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Up-regulation of inflammatory pathway through interleukins and NOS in the geniohyoid muscle in contrast to gastrocnemius muscle in growing rats exposed to intermittent hypoxia (2015)
  • Author(s): Jun Hosomichi, Yo-ichiro Kuma, Shuji Oishi, Risa Usumi-Fujita, Yasuhiro Shimizu, Hideyuki Maeda, Hisashi Nagai, Chisa Shitano, Sawa Kaneko, Yuji Ishida, Jun-ichi Suzuki, Ken-ichi Yoshida, Takashi Ono.
  • Organizer: Sleep 2015
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] マウス抜歯窩に局所適用したRANKL結合ペプチドとBMP-2の併用による骨形成促進作用の評価 (2015)
  • Author(s): 新井祐貴、青木和広、三瀬節子、清水康広、小野卓史、若林則幸
  • Organizer: 第35回日本骨形態計測学会
  • Place of Presentation: 倉敷市芸文館（倉敷市）
  • Year and Date: 2015-06-04
• [Presentation] 成長期ラットにおける間欠的低酸素曝露は、骨成長障害とともに関節頭海綿骨の骨密度増生をもたらす (2014)
  • Author(s): 大石修史、清水康広、細道純、隈陽一郎、前田秀将、臼見莉沙、金香佐和、舌野知佐、鈴木淳一、吉田謙一、小野卓史
  • Organizer: 第73回日本矯正歯科学会大会
  • Place of Presentation: 千葉市、幕張メッセ
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] 成長期の間欠的低酸素曝露は、ラット顎顔面の成長障害とともに舌の肥大および下顎歯列の拡大をもたらす (2014)
  • Author(s): 細道純、隈陽一郎、大石修史、永井恒志、金香佐和、臼見莉沙、清水康広、舌野知佐、石田雄之、鈴木淳一、吉田謙一、小野卓史
  • Organizer: 第73回日本矯正歯科学会大会
  • Place of Presentation: 千葉市、幕張メッセ
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] 骨芽細胞の破骨細胞支持能の獲得におけるプロトンセンサーGPR4の関与 (2014)
  • Author(s): 沖藤明日香、中浜健一、細道純、舌野知佐、臼見莉沙、清水康広、石田雄之、金香佐和、森田育男、小野卓史
  • Organizer: 第73回日本矯正歯科学会大会
  • Place of Presentation: 千葉市、幕張メッセ
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] II 型ウシコラーゲン誘導のマウス関節リウマチモデルを用いたRANKL 結合ペプチドの骨形成促進作用と骨吸収抑制作用 (2014)
  • Author(s): 加藤玄樹、清水康広、菅森泰隆、田村幸彦、小野卓史、大谷啓一、青木和広
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Disturbance of maxillofacial bone growth induced by intermittent hypoxia in growing rats. (2014)
  • Author(s): Shuji Oishi, Yasuhiro Shimizu, Jun Hosomichi, Yo-ichiro Kuma, Hideyuki Maeda, Hisashi Nagai, Sawa Kaneko, Jun-ichi Suzuki, Ken-ichi Yoshida, Takashi Ono.
  • Organizer: Sleep 2014
  • Place of Presentation: Minneapolis (USA)
  • Year and Date: 2014-05-31 – 2014-06-04