Ning Yanyang, Li Weilan, Zou Li, Shen Hongren, Su Zhijian
Department of Endodontics, Changsha Stomatological Hospital, No.389, Youyi Road, Tianxin District, Changsha, 410008, Hunan, China.
Department of Children's Dental Center, Changsha Stomatological Hospital, No.389, Youyi Road, Tianxin District, Changsha, 410008, Hunan, China.
Cell Biochem Biophys. 2025 Mar;83(1):1159-1166. doi: 10.1007/s12013-024-01550-z. Epub 2024 Sep 28.
Periodontitis is a prevalent condition characterized by inflammation and tissue destruction within the periodontium, with hypoxia emerging as a contributing factor to its pathogenesis. Hypoxia-inducible factor 1α (HIF-1α) has a crucial role in orchestrating adaptive responses to hypoxic microenvironments and has been implicated in various inflammatory-related diseases. Understanding the interplay between HIF-1α, matrix metalloproteinases (MMPs), and inflammatory responses in periodontitis could provide insights into its molecular mechanisms. We investigated the relationship between HIF-1α, MMP2, and MMP9 in gingival crevicular fluid (GCF) and periodontal ligament stem cells (PDLSCs) from periodontitis patients. The expression levels of HIF-1α, MMP2, MMP9, and inflammatory factors (IL-6, IL-1β, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Additionally, osteogenic differentiation of PDLSCs was identified by alkaline phosphatase activity. Significantly elevated levels of HIF-1α, MMP2, and MMP9 were observed in GCF of periodontitis patients compared to controls. Positive correlations were found between HIF-1α and MMP2/MMP9, as well as with IL-6, IL-1β, and TNF-α. Modulation of HIF-1α expression in PDLSCs revealed its involvement in MMP2/9 secretion and inflammatory responses, with inhibition of HIF-1α mitigating these effects. Furthermore, HIF-1α inhibition alleviated the reduction in osteogenic differentiation induced by inflammatory stimuli. Our findings elucidate the regulatory role of HIF-1α in MMP expression, inflammatory responses, and osteogenic differentiation in periodontitis. In conclusion, targeting HIF-1α signaling pathways may offer therapeutic opportunities for managing periodontitis and promoting periodontal tissue regeneration.
牙周炎是一种常见病症，其特征为牙周组织内的炎症和组织破坏，缺氧是其发病机制中的一个促成因素。缺氧诱导因子1α（HIF-1α）在协调对缺氧微环境的适应性反应中起关键作用，并与多种炎症相关疾病有关。了解牙周炎中HIF-1α、基质金属蛋白酶（MMPs）和炎症反应之间的相互作用，可为其分子机制提供见解。我们研究了牙周炎患者龈沟液（GCF）和牙周膜干细胞（PDLSCs）中HIF-1α、MMP2和MMP9之间的关系。使用酶联免疫吸附测定（ELISA）和实时聚合酶链反应（RT-PCR）评估HIF-1α、MMP2、MMP9和炎症因子（IL-6、IL-1β、TNF-α）的表达水平。此外，通过碱性磷酸酶活性鉴定PDLSCs的成骨分化。与对照组相比，牙周炎患者GCF中HIF-1α、MMP2和MMP9水平显著升高。发现HIF-1α与MMP2/MMP9以及与IL-6、IL-1β和TNF-α之间呈正相关。对PDLSCs中HIF-1α表达的调节揭示了其参与MMP2/9分泌和炎症反应，抑制HIF-1α可减轻这些作用。此外，HIF-1α抑制减轻了炎症刺激诱导的成骨分化减少。我们的研究结果阐明了HIF-1α在牙周炎中MMP表达、炎症反应和成骨分化中的调节作用。总之，靶向HIF-1α信号通路可能为治疗牙周炎和促进牙周组织再生提供治疗机会。
