{"title":"硫酸吲哚乙酯通过铁氧化作用加剧慢性肾病患者的牙槽骨流失。","authors":"Huiwen Chen, Yining Zhou, Yingli Liu, Wei Zhou, Lina Xu, Dihua Shang, Jing Ni, Zhongchen Song","doi":"10.1111/odi.15050","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.</p><p><strong>Materials and methods: </strong>Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation.</p><p><strong>Results: </strong>Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS.</p><p><strong>Conclusions: </strong>IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"264-277"},"PeriodicalIF":2.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis.\",\"authors\":\"Huiwen Chen, Yining Zhou, Yingli Liu, Wei Zhou, Lina Xu, Dihua Shang, Jing Ni, Zhongchen Song\",\"doi\":\"10.1111/odi.15050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.</p><p><strong>Materials and methods: </strong>Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation.</p><p><strong>Results: </strong>Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS.</p><p><strong>Conclusions: </strong>IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.</p>\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":\" \",\"pages\":\"264-277\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.15050\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15050","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
研究目的本研究旨在确定硫酸吲哚酯（IS）是否参与牙槽骨退化，并阐明慢性肾脏病（CKD）患者牙槽骨丧失的机制：小鼠分为对照组、CP 组（结扎诱发牙周炎）、CKD 组（5/6 肾切除）和 CKD + CP 组。采用高效液相色谱法测定牙龈缝隙液（GCF）中的 IS 浓度。通过显微 CT 评估骨的微观结构。用 IS 刺激 MC3T3-E1 细胞，检测线粒体形态和铁突变相关因子的变化。利用 RT-PCR、Western 印迹、碱性磷酸酶活性测定和茜素红 S 染色来评估 IS 如何影响成骨分化：结果：与其他组相比，CKD + CP 组的牙槽骨破坏更为严重。IS 在 CKD 小鼠的 GCF 中积累。IS 在体外激活芳基烃受体（AhR），抑制 MC3T3-E1 细胞成骨分化，导致线粒体形态改变，并激活 SLC7A11/GPX4 信号通路。AhR抑制剂减轻了IS诱导的上述变化：IS激活了AhR/SLC7A11/GPX4信号通路，抑制了MC3T3-E1细胞的成骨过程，并通过铁蛋白沉积参与了CKD模型小鼠的牙槽骨吸收。
Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis.
Objectives: The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.
Materials and methods: Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation.
Results: Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS.
Conclusions: IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
期刊介绍：
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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