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image of Semaphorin 3A Confers Protection against Oxidative Stress-induced Damage in Periodontal Ligament Stem Cells through the Activation of the Wnt/β-catenin Signaling Pathway

Abstract

Objectives

The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection. This study aimed to investigate the protective effect of Sema3A on the osteogenic differentiation of PDLSCs under OS conditions induced by hydrogen peroxide (HO).

Methods

PDLSCs were subjected to HO treatment to induce OS. The OS indices in PDLSCs were evaluated by analyzing levels of reactive oxygen species (ROS), cell viability, and expression of antioxidant factors using relevant assay kits. A small molecule inhibitor, XAV-939, was employed to block the Wnt/β-catenin pathway. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining for mineralized nodules. Expression levels of osteogenic gene markers and β-catenin were determined real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis.

Results

The stimulation of HO induced OS in PDLSCs, resulting in a downregulation of Sema3A expression and a decrease in osteogenic markers, including ALP activity, mineralized nodule formation, and the expression of osteogenic genes (RUNX2 and ALP). However, the application of recombinant human Sema3A (rhSema3A) counteracted HO-induced OS and restored these osteogenic markers in PDLSCs under OS induced by HO. Mechanistic studies revealed that these effects were associated with an upregulation of β-catenin levels. Moreover, inhibiting β-catenin expression compromised the protective effect of Sema3A on osteogenesis in PDLSCs under OS.

Conclusion

Sema3A exerts a protective effect against HO-induced OS and activates the Wnt/β-catenin pathway to restore osteogenic differentiation impaired by OS in PDLSCs.

© 2025 Bentham Science Publishers
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2025-01-17
2025-05-06

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Semaphorin 3A Confers Protection against Oxidative Stress-induced Damage in Periodontal Ligament Stem Cells through the Activation of the Wnt/β-catenin Signaling Pathway
Bentham Science Publishers ; https://doi.org/10.2174/011574888X343230250107145153
/content/journals/cscr/10.2174/011574888X343230250107145153
/content/journals/cscr/10.2174/011574888X343230250107145153
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  • Article Type:     Research Article
Keywords: osteogenic differentiation ; Wnt/β-catenin pathway ; periodontal ligament stem cells ; oxidative stress ; semaphorin 3A ; Periodontitis

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