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

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

doi:10.1016/j.jare.2023.08.009

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

J Adv Res. 2023 Aug 18:S2090-1232(23)00225-4. doi: 10.1016/j.jare.2023.08.009. Online ahead of print.

Authors

Affiliations

¹ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, China.
² Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; South China Center of Craniofacial Stem Cell Research,510055, Guangzhou, China.
³ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, China. Electronic address: chenzet3@mail.sysu.edu.cn.

PMID: 37597747
DOI: 10.1016/j.jare.2023.08.009

Abstract

Introduction: Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of regenerative dentistry. In light of periodontal development, harnessing the multi-tissue developmental capabilities of periodontal ligament cells (PDLCs) and reinitiating the periodontal developmental process hold great promise as an effective strategy to foster the regeneration of the periodontal complex.

Objectives: This study aims to delve into the potential effects of the macrophage-mediated immune microenvironment on the "developmental engineering" regeneration strategy and its underlying molecular mechanisms.

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.

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.

Keywords: Developmental engineering; Macrophage; Periodontal ligament cells; Periodontal multi-tissue regeneration.