Department of Orthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, School and Hospital of Stomatology, Tongji University, Shanghai, China.
Department of Orthodontic, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
J Oral Pathol Med. 2023 Sep;52(8):786-794. doi: 10.1111/jop.13468. Epub 2023 Jul 25.
Oral breathing has an important impact on morphology and bone mineral density (BMD) in a mandible. This study aimed to investigate the hub genes and mechanism regulating the mandibular BMD decrease induced by nasal obstruction.
A unilateral nasal obstruction model was established in 1-week-old Wistar rats by electrocautery obstruction. BMD of the mandible was determined by micro-computed tomography. Transcriptome analysis was performed to identify differentially expressed genes (DEGs). Hub genes were identified by building protein-protein interaction network and verified by western blot. A hypoxic cell model was established in bone marrow mesenchymal stem cells (BMSCs) by using CoCl2. The expression of hypoxia-inducible factor-1α (HIF-1α), NF-kB ligand-receptor activator (RANKL), osteoprotegerin (OPG), and Cyp1a1 was detected by western blot.
The mandibular BMD of rats in the unilateral nasal obstruction group was significantly decreased. A total of 38 DEGs were identified in nasal obstruction rats compared with normal rats. A ratio of RANKL/OPG in the mandible was elevated by nasal obstruction, while the Cyp1a1 was decreased. In vitro, the HIF-1α expression and RANKL/OPG ratio were upregulated by hypoxia while the Cyp1a1 expression was decreased. Pretreatment with Cyp1a1 activator, FICZ, could increase the expression of Cyp1a1 while attenuating the activation of HIF-1α and RANKL.
Respiratory changes caused by nasal obstruction contribute to the decrease in Cyp1a1 expression in the mandible of juvenile rats, which is associated with disturbances in bone homeostasis controlled by the RANKL/OPG ratio.
口腔呼吸对下颌骨形态和骨密度（BMD）有重要影响。本研究旨在探讨鼻阻塞引起下颌骨 BMD 下降的调节机制。
采用电灼法阻塞 1 周龄 Wistar 大鼠单侧鼻腔，建立单侧鼻阻塞模型。采用微计算机断层扫描法测定下颌骨 BMD。采用转录组分析鉴定差异表达基因（DEGs）。通过构建蛋白质-蛋白质相互作用网络鉴定关键基因，并通过 Western blot 进行验证。采用 CoCl2 建立骨髓间充质干细胞（BMSCs）缺氧模型。采用 Western blot 检测缺氧诱导因子-1α（HIF-1α）、核因子-kB 配体-受体激活剂（RANKL）、骨保护素（OPG）和细胞色素 P4501A1（Cyp1a1）的表达。
单侧鼻阻塞组大鼠下颌骨 BMD 明显降低。与正常组大鼠相比，鼻阻塞组大鼠共鉴定出 38 个 DEGs。鼻阻塞使下颌骨 RANKL/OPG 比值升高，Cyp1a1 表达降低。体外，缺氧可上调 HIF-1α表达和 RANKL/OPG 比值，降低 Cyp1a1 表达。Cyp1a1 激活剂 FICZ 预处理可增加 Cyp1a1 表达，同时抑制 HIF-1α和 RANKL 的激活。
鼻阻塞引起的呼吸变化导致幼年大鼠下颌骨 Cyp1a1 表达减少，这与 RANKL/OPG 比值控制的骨稳态紊乱有关。
