2. Academic Validation
  3. BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway

BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway

  • BMC Oral Health. 2024 Jan 8;24(1):40. doi: 10.1186/s12903-023-03827-w.
Yao Xu 1 2 3,  Yi Chu 1 2,  Wanrong Yang 1 2,  Kefei Chu 1 2,  Sihui Li 1 2,  Ling Guo 4 5
Affiliations

Affiliations

  • 1 Luzhou Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, China.
  • 2 Department of Oral prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, China.
  • 3 The people's hospital of pengzhou, Chengdu, China.
  • 4 Luzhou Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, China. [email protected].
  • 5 Department of Oral prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, China. [email protected].
PMID: 38191432 DOI: 10.1186/s12903-023-03827-w
Abstract

Background: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related Pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms.

Methods: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism.

Results: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related Pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway.

Conclusion: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related Pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis.

Keywords

Lipoxin A4 analog; NLRP3; Nrf2; Pyroptosis; Reactive oxygen species.

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