2. Academic Validation
  3. Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis

Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis

  • Oral Dis. 2024 Jun 27. doi: 10.1111/odi.15050.
Huiwen Chen 1 2,  Yining Zhou 1 2,  Yingli Liu 3,  Wei Zhou 2 4,  Lina Xu 1 2,  Dihua Shang 1 2,  Jing Ni 1 2,  Zhongchen Song 1 2
Affiliations

Affiliations

  • 1 Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
  • 3 Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 38934473 DOI: 10.1111/odi.15050
Abstract

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.

Keywords

alveolar bone; aryl hydrocarbon receptor; chronic kidney disease; ferroptosis; indoxyl sulfate.

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