Inducing the "re-development state" of periodontal ligament cells via tuning macrophage mediated immune microenvironment

调控巨噬细胞介导的免疫微环境诱导牙周膜细胞“重新发育状态”

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作者:Guanqi Liu, Linjun Zhang, Xuan Zhou, Junlong Xue, Ruidi Xia, Xuejing Gan, Chunxiao Lv, Yanshu Zhang, Xueli Mao, Xiaoxing Kou, Songtao Shi, Zetao Chen

Conclusion

The results of this study could provide some favorable theoretical bases for applying periodontal development engineering strategy in resolving the difficulties in periodontal multi-tissue regeneration.

Methods

In this study, we conducted a comprehensive examination of the periodontium developmental process in the rat mandibular first molar using histological staining. Through the induction of diverse immune microenvironments in macrophages, we evaluated their potential effects on periodontal re-development events using a cytokine array. Additionally, we investigated PDLC-mediated periodontal re-development events under these distinct immune microenvironments through transcriptome sequencing and relevant functional assays. Furthermore, the underlying molecular mechanism was also performed.

Results

The activation of development-related functions in PDLCs proved challenging due to their declined activity. However, our findings suggest that modulating the macrophage immune response can effectively regulate PDLCs-mediated periodontium development-related events. The M1 type macrophage immune microenvironment was found to promote PDLC activities associated with epithelial-mesenchymal transition, fiber degradation, osteoclastogenesis, and inflammation through the Wnt, IL-17, and TNF signaling pathways. Conversely, the M2 type macrophage immune microenvironment demonstrated superiority in inducing epithelium induction, fibers formation, and mineralization performance of PDLCs by upregulating the TGFβ and PI3K-Akt signaling pathway.

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