幼若ラットモデルにおいて、鼻閉は歯槽骨の破壊を促進する

Nasal obstruction promotes alveolar bone destruction in the juvenile rat model.

抄録

背景・目的:

鼻閉は口呼吸を引き起こし、結果として低酸素症になる。本研究の目的は、鼻閉により口呼吸を誘発したラットモデルにおいて、低酸素が炎症反応に及ぼす影響と歯槽骨の発育に及ぼす影響を明らかにすることである。

Background/purpose: Nasal obstruction leads to oral breathing and consequently hypoxia. The purpose of this study was to determine the influence of hypoxia on inflammatory response and the effect on alveolar bone development in a rat model in which mouth breathing was induced by nasal obstruction.

材料および方法:

Materials and methods: Unilateral nasal obstruction was performed by injecting a Merocel sponge into the nasal cavity of 8-week-old Sprague Dawley (SD) rats. After 3 and 6 weeks of nasal obstruction, rats were sacrificed, the organs were weighed, and the changes in mandibular bone quality were examined by micro-computed tomography (μ-CT). The stereomicroscope was used for the morphological analysis of alveolar bone loss in response to nasal obstruction. Hematoxylin and Eosin (H&E) and immunohistochemical staining were employed to examine inflammation and bone remodeling induced by hypoxia.

結果:

鼻閉により、全身の成長や器官の発達に遅れが生じた。下顎骨の骨密度（BMD）および骨量／総体積（BV/TV）は鼻閉により減少し、歯槽骨の欠損が形態学的に確認された。鼻腔閉塞法は、低酸素誘導因子1α（HIF-α）の増加を伴う低酸素誘導に成功することが確認された。経鼻閉塞による経口低酸素症は炎症反応を亢進させ、receptor activator of nuclear factor kappa-Β ligand（RANKL）の発現を増加させ、骨破壊に至らせた。

Results: Nasal obstruction led to a delay in overall growth and organ development. The bone mineral density (BMD) and bone volume/total volume (BV/TV) of the mandible were reduced due to nasal obstruction, and the loss of the alveolar bone was confirmed morphologically. Our nasal obstruction method was observed to be successful in inducing hypoxia along with an increase in hypoxia-inducible factor 1-alpha (HIF-α). Oral hypoxia induced by nasal obstruction increased inflammatory response, and increased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) led to bone destruction.

結論:

本研究により、鼻閉による口呼吸が低酸素状態を引き起こすことが、ラットモデルで実証された。低酸素状態では、炎症経路の活性化により破骨細胞の分化が増加し、歯槽骨の破壊的な変化を引き起こす。

Conclusion: This study demonstrated that nasal obstruction induced mouth breathing led to hypoxia in a rat model. Under hypoxic conditions, an increase in osteoclast differentiation induced by activation of the inflammatory pathway causes destructive changes in the alveolar bone.