Basic research of tissue engineering for TMJ using immortalized TMJ disc cell clones

• Project/Area Number: 25463170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hosomichi Jun 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (00420258)
• Co-Investigator(Kenkyū-buntansha): YONEMITSU Ikuo 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00431940) ; SHIMIZU Yasuhiro 東京医科歯科大学, 歯学部附属病院, 医員 (60631968)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 顎骨低形成 / 骨軟骨破壊 / 顎関節 / 劣成長 / 顎骨成長 / 低酸素 / 顎関節低成長 / 小児性睡眠時無呼吸症候群 / 間欠的低酸素暴露 / HIFs / オートファジー

Outline of Final Research Achievements

Our first purpose was to clarify the mechanism of osteoarthritis in TMJ, leading to disturb TMJ regeneration in adults, especially in female adults. We checked cell responses of TMJ disc clone cells to female hormone, relaxin. Relaxin enhanced the expression of RXFP1/2 in fibroblast-like clones. It caused a greater induction of MMP9/13 in fibroblast- than in chondrocyte-like clones. Our second purpose was to examine the role of intermittent hypoxia (IH) observed in pediatric obstructive sleep apnea (OSA) in dentofacial morphological changes in growing rats. We demonstrated that IH induces the formation of a smaller mandible and larger tongue in peripubertal rats, consistent with children with OSA who exhibit macroglossia and retrognathia, as well as discrepant growth in the transverse dental arch. Mandibular growth persists during adolescence, suggesting that IH induces earlier intramembranous ossification and growth delay in the mandible in growing rats.

Research Products

• [Journal Article] Intermittent hypoxia causes mandibular growth retardation and macroglossia in growing rats. (2016)
  • Author(s): Hosomichi J, Kuma K, Oishi S, Nagai H, Maeda H, Usumi-Fujita R, Shimizu Y, Kaneko S, Shitano C, Suzuki J, Yoshida K, Ono T.
  • Journal Title: American Journal of Orthodontics and Dentofacial Orthopedics Volume: In press
  • Peer Reviewed / Acknowledgement Compliant
• [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] Immortalization and characterization of mouse - temporomandibular joint disc cell clones with capacity for multi-lineage differentiation. (2015)
  • Author(s): Park Y, Hosomichi J, Ge C, Xu J, Franceschi R, Kapila S.
  • Journal Title: Osteoarthritis Cartilage. Volume: - Issue: 9 Pages: 1532-1542
  • DOI: 10.1016/j.joca.2015.04.006
  • 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
• [Journal Article] Soft diet causes greater alveolar osteopenia in the mandible than in the maxilla. (2013)
  • Author(s): Yasuhiro Shimizu, Takayoshi Ishida, Jun Hosomichi, Sawa Kaneko, Kasumi Hatano, and Takashi Ono
  • Journal Title: Archives of Oral Biology Volume: 未 Issue: 8 Pages: 907-11
  • DOI: 10.1016/j.archoralbio.2013.02.003
  • Peer Reviewed
• [Journal Article] Mechanisms for relaxin's modulation of MMPs and matrix loss in fibrocartilages. (2013)
  • Author(s): Kapila S, Park Y, Ahmad N, Hosomichi J, Hayami T, Tacon C.
  • Journal Title: Ital J Anat Embryol. Volume: 118 Pages: 62-65
  • Peer Reviewed
• [Presentation] Intermittent hypoxia influences bone microstructure via hypoxia inducible factor and VEGF in growing rats (2016)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Maeda H, Nagai H, Kaneko S, Ishida Y, Shibutani N, Usumi-Fujita R, Yamaguchi H, Suzuki J, Yoshida K, Ono T.
  • Organizer: 10th Asia Pacific Orthodontic Congress
  • Place of Presentation: インドネシア・バリ
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [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. (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, 隈陽一郎, 中井雄太, 鈴木淳一, 前田秀将, 吉田謙一, 小野卓史.
  • Organizer: 第74回日本矯正歯科学会大会
  • Place of Presentation: マリンメッセ福岡・福岡県福岡市
  • Year and Date: 2015-11-20
• [Presentation] Intermittent hypoxia triggers inflammatory pathway with down-regulated myofibrillar and mitochondrial biogenesis in the geniohyoid muscle. (2015)
  • Author(s): Hosomichi J, Nakai Y, Maeda H, Kuma Y, Oishi S, Usumi-Fujita R, Shimizu Y, Kaneko S, Ishida Y, Shibutani N, Yoshida K, Ono T.
  • Organizer: The 74th Annual Meeting of the Japanese Orthodontic Society
  • Place of Presentation: 福岡国際会議場・福岡県福岡市
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] Up-regulation of inflammatory pathway through interleukins and NOS in the geniohyoid muscle. (2015)
  • Author(s): Hosomichi J, Oishi S, Kuma Y, Maeda H, Nagai Y, Kaneko S, Shitani C, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP 2015
  • Place of Presentation: アメリカ・シアトル
  • Year and Date: 2015-06-15
  • 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): Hosomichi J, Kuma Y, Oishi S, Usumi-Fujita R, Shimizu Y, Maeda H, Nagai H, Shitano C, Kaneko S, IshidaY, Suzuki J, Yoshida K, Ono T.
  • Organizer: 29th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06 – 2015-06-10
• [Presentation] Intermittent hypoxia effects the angiogenic factor and structure of nasal cavity. (2015)
  • Author(s): Kuma Y, Usumi-Fujita R, Hosomichi J, Oishi S, Nagai H, Maeda H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: 29th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06 – 2015-06-10
• [Presentation] Intermittent hypoxia induces the impaired microstructure of the growing craniofacial bone. (2015)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, KumaY, Usumi-Fujita R, Maeda H, Nagai H, Shitano C, Kaneko S, Ishida Y, Suzuki J, Yoshida K, Ono T.
  • Organizer: 29th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-06-06 – 2015-06-10
• [Presentation] Impairment of nasal airway under intermittent hypoxia during growth period in rats. (2015)
  • Author(s): Kuma Y, Usumi-Fujita R, Hosomichi J, Oishi S, Nagai Y, Maeda H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP 2015
  • Place of Presentation: アメリカ・シアトル
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] The effects of intermittent hypoxia on the microstructure of growing craniofacial bones. (2015)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Maeda H, Nagai Y, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP 2015
  • Place of Presentation: アメリカ・シアトル
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Intermittent hypoxia induces impaired craniofacial and muscular growths in rats. (2015)
  • Author(s): Hosomichi J, Kuma Y, Oishi S, Nagai H, Maeda H, Kaneko S, Usumi-Fujita R, Shimizu Y, Ishida Y, Suzuki J, Yoshida K, Ono T.
  • Organizer: 2015 IADR/AADR/CADR General Session & Exhibition
  • Place of Presentation: Boston (USA)
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] Mechanisms for relaxin’s modulation of fibrocartilage MMPs and matrix loss. (2015)
  • Author(s): Kapila S, Park Y, Ahmad N, Hosomichi J, Hayami T, Xu J.
  • Organizer: 2015 IADR/AADR/CADR General Session & Exhibition
  • Place of Presentation: Boston (USA)
  • Year and Date: 2015-03-11 – 2015-03-14
• [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: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2014-10-20 – 2014-10-22
• [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: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] Intermittent-hypoxia-induced expression of autophagy accelerates BNIP3 in the geniohyoid muscles in contrast to gastrocnemius muscle in rats. (2014)
  • Author(s): Hosomichi J, Oishi S, Kuma Y, Maeda H, Nagai H, Kaneko S, Shitano C, Suzuki J, Yoshida K, Ono T.
  • Organizer: 28th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Minneapolis (USA)
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] Growth impairment of nasal airway under intermittent hypoxia during growth period in rats. (2014)
  • Author(s): Kuma Y, Usumi-Fujita R, Hosomichi J, Oishi S, Nagai H, Maeda H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: 28th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Minneapolis (USA)
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] The Intermittent hypoxia induced discrepancy of bone growth and density in rat maxillofacial bone. (2014)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Maeda H, Nagai H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: 28th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Minneapolis (USA)
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] Intermittent-hypoxia-induced expression of autophagy accelerates BNIP-3 in the geniohyoid muscles in contrast to gastrocnemius muscle in rats (2014)
  • Author(s): Hosomichi J, Oishi S, Kuma Y, Maeda H, Nagai H, Kaneko S, Shitano C, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP 2014
  • Place of Presentation: ミネアポリス・アメリカ
• [Presentation] Disturbance of maxillofacial bone growth induced by intermittent hypoxia in growing rats (2014)
  • Author(s): Oishi S, Shimizu Y, Hosomichi J, Kuma Y, Maeda H, Nagai H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP 2014
  • Place of Presentation: ミネアポリス・アメリカ
• [Presentation] Growth impairment of nasal airway under intermittent hypoxia during growth period in rats (2014)
  • Author(s): Kuma Y, Usumi-Fujita R, Hosomichi J, Oishi S, Nagai H, Maeda H, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: SLEEP2014
  • Place of Presentation: ミネアポリス・アメリカ
• [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）
• [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）
• [Presentation] Alveolar bone loss induced by hypofunctional tooth movement in rats (2013)
  • Author(s): C. SHITANO, O. BABA, S. KANEKO, J. HOSOMICHI, Y. SHIMIZU, N. SHIBUTANI, R. USUMI-FUJITA, Y. T AKANO, T. ONO
  • Organizer: 第61回JADR＆第2回IADR Asia Pacific Region
  • Place of Presentation: バンコク・タイ
• [Presentation] 成長期における間欠的低酸素がラット鼻腔気道の三次元形態に与える影響 (2013)
  • Author(s): 隈陽一郎、臼見莉沙、細道純、大石修史、永井恒志、清水康広、金香佐和、舌野知佐、鈴木淳一、吉田謙一、小野卓史
  • Organizer: 第72回日本矯正歯科学会大会
  • Place of Presentation: 松本市(キッセイ文化ホール・松本市総合体育館)
• [Presentation] 間欠的低酸素はラット顎顔面領域の骨成長を抑制し形態の不調和をもたらす (2013)
  • 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72回日本矯正歯科学会大会
  • Place of Presentation: 松本市(キッセイ文化ホール・松本市総合体育館)