The study to clarify the mechanism of mandibular growth retardation regulated by central mediators for bone formation in pediatric obstructive sleep apnea

• Project/Area Number: 15K15753
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ONO Takashi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30221857)
• Co-Investigator(Kenkyū-buntansha): 吉田 謙一 東京医科大学, 医学部, 主任教授 (40166947) ; 清水 康広 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) ; 鈴木 淳一 東京大学, 医学部附属病院, 特任准教授 (90313858) ; 臼見 莉沙 東京医科歯科大学, 歯学部附属病院, 特任助教 (90706946)
• Co-Investigator(Renkei-kenkyūsha): HOSOMICHI Jun 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00420258)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児期閉塞性睡眠時無呼吸症候群 / 間欠的低酸素曝露 / 成長期動物 / 閉塞性睡眠時無呼吸症候群 / 小児 / 顎顔面成長障害 / 成長期ラットモデル / 骨代謝 / 小児睡眠時無呼吸症候群 / 交感神経受容体 / 顎骨

Outline of Final Research Achievements

Repetitive episodes of hypoxia during sleep is a pathology of obstructive sleep apnea (OSA). However, the mechanism of impaired craniofacial growth caused by intermittent hypoxia (IH) is unknown. The aim of this study was to demonstrate the role of the β2-adrenergic receptor in the craniofacial growth retardation of adolescent rats exposed to IH. Seven-week-old male rats underwent 20 cycles of IH (nadir of 4% oxygen to peak of 21% oxygen) for 8 hours each day for 3 weeks. Rats were medicated with a β2-adrenergic antagonist (butoxamine) intraperitoneally. The control rats were exposed to room air, and administrated with saline intraperitoneally. IH caused mandibular growth retardation and a significant increase in bone mineral density (BMD). Butoxamine attenuated mandibular growth retardation, especially in the posterior part and also increases BMD in the condylar head and gene expression level of RANKL in the IH group.

Research Products

• [Presentation] The impact of a ß2-adrenergic antagonist, butoxamine on mandibular growth retardation caused by intermittent hypoxia in growing rats. (2018)
  • Author(s): Hong H, Hosomichi J, Maeda H, Kochakorn L, Oishi S, Kuma Y, Yamaguchi H, Ishida Y, Suzuki J, Yoshida K, Ono T.
  • Organizer: The 11th Asian Pacific Orthodontic Conference
  • Int'l Joint Research
• [Presentation] The impact of a ß2-adrenergic antagonist, butoxamine on mandibular growth retardation caused by intermittent hypoxia in growing rats. (2018)
  • Author(s): Hong H, Hosomichi J, Maeda H, Kochakorn L, Oishi S, Kuma Y, Yamaguchi H, Ishida Y, Suzuki J, Yoshida K, Ono T.
  • Organizer: 第5回東京医科大学記念会館ポスター発表懇談会
• [Presentation] β2-adrenergic antagonist butoxamine reduces the mandibular growth retardation caused by intermittent hypoxia in adolescent rats. (2018)
  • Author(s): ong H, Hosomichi J, Maeda H, Kochakorn L, Oishi S, Kuma Y, Yamaguchi H, Ishida Y, Usumi-Fujita R, Shimizu Y, Kaneko S, Suzuki J, Yoshida K, Ono T.
  • Organizer: The 7th Joint Meeting of the Japanese Orthodontic Society and Korean Association of Orthodontists
  • Int'l Joint Research