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Background <p>To explore the potential role of cGAS-STING/GPX4 axis-mediated ferroptosis in cementoblast mineralization under compressive force and to determine its involvement in orthodontically induced inflammatory external root resorption (OIIERR).</p> Methodology <p>An immortalized murine cementoblast cell line (OCCM-30) was subjected to a 2&#xa0;g/cm<sup>2</sup> compressive force for 24&#xa0;h to establish an in vitro loading model. Western blot was used to detect proteins associated with mineralization (RUNX2, OPN, OCN) and components of the cGAS-STING/GPX4 axis. Ferroptosis was assessed by measuring ROS, Fe<sup>2+</sup>, and MDA levels. Mitochondrial damage was examined via mitochondrial membrane potential analysis and mtDNA linkage evaluation. To further investigate the role of cGAS-STING/GPX4 axis-mediated ferroptosis, STING knockdown and Ferrostatin-1 (Fer-1) were employed. In vivo, an OIIERR mouse model was established, and the STING inhibitor H-151 was administered to assess the involvement of cGAS-STING/GPX4 axis-mediated ferroptosis in OIIERR.</p> Results <p>Compressive force significantly reduced RUNX2, OPN, OCN, and GPX4 expression, while increasing ROS, Fe<sup>2+</sup>, and MDA levels. Mitochondrial dysfunction, including decreased membrane potential and cytoplasmic mtDNA leakage, was observed. Western blot analysis showed that compressive force significantly upregulated cGAS, p-STING, p-TBK1 and p-IRF3 in OCCM-30 cells. Knockdown of STING or Fer-1 treatment restored mineralization under compressive force. In vivo, immunohistochemical staining confirmed the activation of cGAS-STING/GPX4 axis in the OIIERR group. Notably, administration of H-151 reduced the expression of pathway-related proteins and effectively mitigated root resorption.</p> Conclusions <p>Compressive force inhibits cementoblast mineralization by inducing ferroptosis via the cGAS-STING/GPX4 axis. Furthermore, H-151 effectively suppresses OIIERR in mice. Targeting cGAS-STING/GPX4 axis-mediated ferroptosis may serve as a potential therapeutic strategy for OIIERR treatment.</p>

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Ferroptosis inhibits cementoblast mineralization via cGAS-STING/GPX4 axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月13日

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  • Tian Wei,
  • Dongyang Li,
  • Jie Zhang,
  • Zhe Zhou,
  • Chunmiao Jiang

摘要

Background

To explore the potential role of cGAS-STING/GPX4 axis-mediated ferroptosis in cementoblast mineralization under compressive force and to determine its involvement in orthodontically induced inflammatory external root resorption (OIIERR).

Methodology

An immortalized murine cementoblast cell line (OCCM-30) was subjected to a 2 g/cm2 compressive force for 24 h to establish an in vitro loading model. Western blot was used to detect proteins associated with mineralization (RUNX2, OPN, OCN) and components of the cGAS-STING/GPX4 axis. Ferroptosis was assessed by measuring ROS, Fe2+, and MDA levels. Mitochondrial damage was examined via mitochondrial membrane potential analysis and mtDNA linkage evaluation. To further investigate the role of cGAS-STING/GPX4 axis-mediated ferroptosis, STING knockdown and Ferrostatin-1 (Fer-1) were employed. In vivo, an OIIERR mouse model was established, and the STING inhibitor H-151 was administered to assess the involvement of cGAS-STING/GPX4 axis-mediated ferroptosis in OIIERR.

Results

Compressive force significantly reduced RUNX2, OPN, OCN, and GPX4 expression, while increasing ROS, Fe2+, and MDA levels. Mitochondrial dysfunction, including decreased membrane potential and cytoplasmic mtDNA leakage, was observed. Western blot analysis showed that compressive force significantly upregulated cGAS, p-STING, p-TBK1 and p-IRF3 in OCCM-30 cells. Knockdown of STING or Fer-1 treatment restored mineralization under compressive force. In vivo, immunohistochemical staining confirmed the activation of cGAS-STING/GPX4 axis in the OIIERR group. Notably, administration of H-151 reduced the expression of pathway-related proteins and effectively mitigated root resorption.

Conclusions

Compressive force inhibits cementoblast mineralization by inducing ferroptosis via the cGAS-STING/GPX4 axis. Furthermore, H-151 effectively suppresses OIIERR in mice. Targeting cGAS-STING/GPX4 axis-mediated ferroptosis may serve as a potential therapeutic strategy for OIIERR treatment.