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Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells

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Abstract

Periodontitis is characterized by alveolar bone destruction and is one of the most common chronic oral diseases. Inflammatory cytokines released by pyroptosis, which can be triggered by oxidative stress, are critical in the development of periodontitis. This study aims to clarify whether oxidative stress causes osteoblast dysfunction by inducing pyroptosis in the process of periodontitis. We found that treatment with lipopolysaccharide (LPS) led to NLRP3 inflammasome-mediated pyroptosis of MG63 cells as well as decreased cell migration. Of note, LPS stimulation increased LDH release in a time- and dose-dependent manner. However, inhibition of reactive oxygen species with N-acetyl-L-cysteine attenuated oxidative stress-mediated pyroptosis and improved migration injury in osteoblasts treated with LPS. Further, inhibition of the NLRP3 inflammasome with MCC950 improved osteoblast migration and restored the expression of osteogenic differentiation-related proteins such as COL 1, RUNX 2 and ALP. In conclusion, oxidative stress caused by LPS induces pyroptosis in osteoblasts, leading to osteogenic dysfunction.

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Abbreviations

LPS:

Lipopolysaccharides

ROS:

Reactive oxygen species

LDH:

Lactate dehydrogenase

NAC:

N-acetyl-L-cysteine

SOD:

Superoxide dismutase

GSH:

Glutathione peroxidase

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Acknowledgements

This study was partially supported by the National Nature Science Foundation of China (Grant Nos. 81972072; 81470719; 81611140133) to Li M; Shandong Key Research and development Project (Grant No. 2018GSF118114) to Li M. This research was also supported by Open Foundation of Shandong Key Laboratory of Oral Tissue Regeneration (Grant No. SDKQ201903) to Du J, Jinan Clinical Medicine and Technology Innovation Programme (Grant No. 201704121) to Zhou W.

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Shanshan Liu contributed most to this work and should be considered first authors. Minqi Li conceived and designed the study should be considered as Corresponding authors; Shanshan Liu and Juan Du analyzed the data; Dongfang Li, Panpan Yang and Qin Zhou made the diagrams and tables of the article; Yuying Kou, Congshan Li and Tomoka Hasegawa wrote the paper.

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Correspondence to Minqi Li.

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Liu, S., Du, J., Li, D. et al. Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells. J Mol Hist 51, 221–232 (2020). https://doi.org/10.1007/s10735-020-09874-9

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  • DOI: https://doi.org/10.1007/s10735-020-09874-9

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