Details

Autor(en) / Beteiligte

• Bao, Jiaqi
• Wang, Zhongxiu
• Yang, Yuting
• Yu, Xufei
• Yuan, Wenlin
• Sun, Weilian
• Chen, Lili

Titel

Interleukin‐17 alleviates erastin‐induced alveolar bone loss by suppressing ferroptosis via interaction between NRF2 and p‐STAT3

Ist Teil von

• Journal of clinical periodontology, 2024-02, Vol.51 (2), p.233-250

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2024

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Aim To investigate the relationship between interleukin‐17 (IL‐17), ferroptosis and osteogenic differentiation. Materials and Methods We first analysed the changes in ferroptosis‐related molecules in experimental periodontitis models. The effects of erastin, a small‐molecule ferroptosis inducer, and IL‐17 on alveolar bone loss and repair in animal models were then investigated. Primary mouse mandibular osteoblasts were exposed to erastin and IL‐17 in vitro. Ferroptosis‐ and osteogenesis‐related genes and proteins were detected. Further, siRNA, immunofluorescence co‐localization and immunoprecipitation were used to confirm the roles of the nuclear factor erythroid‐2‐related factor 2 (NRF2) and phosphorylated signal transducer and activator of transcription 3 (p‐STAT3), as well as their interaction. Results The levels of NRF2, glutathione peroxidase 4 and solute carrier family 7 member 11 were lower in the ligated tissues than in normal periodontal tissues. Alveolar bone loss in an in vivo experimental periodontitis model was aggravated by erastin and alleviated by IL‐17. In vitro, IL‐17 ameliorated erastin‐inhibited osteogenic differentiation by reversing ferroptosis. Altered NRF2 expression correlated with changes in ferroptosis‐related molecules and osteogenesis. Furthermore, the physical interaction between NRF2 and p‐STAT3 was confirmed in the nucleus. In IL‐17 + erastin‐stimulated osteoblasts, the p‐STAT3–NRF2 complex might actively participate in the downstream transcription of ferroptosis‐ and osteogenesis‐related genes. Conclusions IL‐17 administration conferred resistance to erastin‐induced osteoblast ferroptosis and osteogenesis. The possible mechanism may involve p‐STAT3 directly interacting with NRF2.