Validation of serotonin-targeted cartilaginous bone dysplasia in pediatric sleep apnea animal model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10223
• 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: Tokyo Medical and Dental University
• Principal Investigator: Hosomichi Jun 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00420258)
• Co-Investigator(Kenkyū-buntansha): 下澤 達雄 国際医療福祉大学, 医学部, 主任教授 (90231365) ; 前田 秀将 東京医科大学, 医学部, 准教授 (60407963)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 閉塞性睡眠時無呼吸症 / 小児 / 交感神経 / 骨軟骨代謝 / 間欠的低酸素状態

Outline of Final Research Achievements

Activation of the sympathoadrenal system is associated with sleep apnea-related symptoms and metabolic dysfunction induced by chronic intermittent hypoxia (IH). IH can induce hormonal imbalances and growth retardation of the craniofacial bones. However, the relationship between IH and β2-adrenergic receptor signaling in the context of skeletal growth regulation is unclear. This study aimed to investigate the role of β2-adrenergic receptors in IH-induced mandibular growth retardation and bone metabolic alterations. Recovery of RANKL expression was observed in IH-exposed rats administered with butoxamine. Collectively, our findings suggest that the activation of β2-adrenergic receptors and leptin signaling during growth may be involved in IH-induced skeletal growth retardation of the mandible, which may be mediated by concomitant changes in RANKL expression at the growing condyle.

Free Research Field

歯科矯正学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の成果は、IH 曝露に伴う顎顔面成長障害の新たな病態機構を示すともに、小児OSA 患者における顎の形や大きさの不調和に対する治療法開発の糸口となることが期待される。