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Aim <p>The Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy and the Acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid peroxidation promote ferroptosis. Nuclear factor erythroid-2 related factor-2 (Nrf2), a transcription factor, controls antioxidants, detoxifying enzymes, and ferroptosis. The concerted activity of NCOA4, ACSL4, and Nrf2 in periodontitis associated with or without T2DM needs exploration.</p> Materials and methods <p>Forty-two patients were recruited and categorized into 3 groups: Group I: systemically and periodontally healthy (PH, <i>n</i> = 14); Group II: Stage III/IV Periodontitis (PD, <i>n</i> = 14); Group III: Stage III/IV Periodontitis with uncontrolled Type 2 Diabetes mellitus (T2DM + DM, <i>n</i> = 14). The site-specific periodontal clinical parameters were recorded. Gingival tissue biopsies were evaluated for gene expression of NCOA4, Nrf2, and ACSL4 by real time -PCR.</p> Results <p>In groups II and III, NCOA4 expression increased by 10.07 ± 9.15 and 9.40 ± 6.29-fold, respectively, whereas ACSL4 expression increased by 3.23 ± 2.53 and 2.03 ± 2.22-fold, respectively, compared to group I (<i>P</i> &lt; 0.05). Nrf2 expression decreased in groups II (0.36 ± 0.39) and III (0.83 ± 0.89) compared to group I, with the least expression in group II. In the total sample analysis, NCOA4 FC and Nrf2 CT showed a significant positive correlation with all clinical parameters and with each other (<i>P</i> &lt; 0.05). There was a significant positive correlation (<i>P</i> &lt; 0.05) between NCOA4 FC and ACSL4 CT (<i>P</i> &lt; 0.05). In group II, NCOA4 CT had significant positive and negative correlations with Nrf2 FC and ACSL4 FC values, respectively (<i>P</i> &lt; 0.05). The diagnostic accuracy of NCOA4 and Nrf2 in differentiating between periodontal health and periodontitis was 89% (AUC = 0.96) and 71% (AUC = 0.60), respectively. Likewise, NCOA4 and Nrf2 demonstrated diagnostic accuracy of 67.8% (AUC = 0.73) and 78.5% (AUC = 0.85) in differentiating between diabetic periodontitis and periodontal health, respectively.</p> Conclusions <p>Ferroptosis in the progression of periodontitis and diabetes-associated periodontitis may be linked to dysregulated expressions of the NCOA4, ACSL4, and Nrf2 genes. However, additional investigation is required to fully comprehend the findings.</p>

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Comparative evaluation of ferroptosis markers NCOA4, ACSL4, and Nrf2 in periodontitis with and without type 2 diabetes mellitus: a case-control study

  • 期刊论文

  • 发表日期：

    2025年11月29日

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  • Sriram Premkumar,
  • Devapriya Appukuttan,
  • Jaganathan Ranjit Kumar,
  • Santhosh Venkadassalapathy,
  • Sangeetha Subramanian,
  • PSG Prakash,
  • Dhayanand John Victor

摘要

Aim

The Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy and the Acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid peroxidation promote ferroptosis. Nuclear factor erythroid-2 related factor-2 (Nrf2), a transcription factor, controls antioxidants, detoxifying enzymes, and ferroptosis. The concerted activity of NCOA4, ACSL4, and Nrf2 in periodontitis associated with or without T2DM needs exploration.

Materials and methods

Forty-two patients were recruited and categorized into 3 groups: Group I: systemically and periodontally healthy (PH, n = 14); Group II: Stage III/IV Periodontitis (PD, n = 14); Group III: Stage III/IV Periodontitis with uncontrolled Type 2 Diabetes mellitus (T2DM + DM, n = 14). The site-specific periodontal clinical parameters were recorded. Gingival tissue biopsies were evaluated for gene expression of NCOA4, Nrf2, and ACSL4 by real time -PCR.

Results

In groups II and III, NCOA4 expression increased by 10.07 ± 9.15 and 9.40 ± 6.29-fold, respectively, whereas ACSL4 expression increased by 3.23 ± 2.53 and 2.03 ± 2.22-fold, respectively, compared to group I (P < 0.05). Nrf2 expression decreased in groups II (0.36 ± 0.39) and III (0.83 ± 0.89) compared to group I, with the least expression in group II. In the total sample analysis, NCOA4 FC and Nrf2 CT showed a significant positive correlation with all clinical parameters and with each other (P < 0.05). There was a significant positive correlation (P < 0.05) between NCOA4 FC and ACSL4 CT (P < 0.05). In group II, NCOA4 CT had significant positive and negative correlations with Nrf2 FC and ACSL4 FC values, respectively (P < 0.05). The diagnostic accuracy of NCOA4 and Nrf2 in differentiating between periodontal health and periodontitis was 89% (AUC = 0.96) and 71% (AUC = 0.60), respectively. Likewise, NCOA4 and Nrf2 demonstrated diagnostic accuracy of 67.8% (AUC = 0.73) and 78.5% (AUC = 0.85) in differentiating between diabetic periodontitis and periodontal health, respectively.

Conclusions

Ferroptosis in the progression of periodontitis and diabetes-associated periodontitis may be linked to dysregulated expressions of the NCOA4, ACSL4, and Nrf2 genes. However, additional investigation is required to fully comprehend the findings.