Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells

Lyu, Ping; Song, Yiming; Bi, Ruiye; Li, Zucen; Wei, Yali; Huang, Qin; Song, Dongzhe; Zhou, Xuedong; Fan, Yi

doi:10.3390/biom12121737

Cited by 7 publications

(5 citation statements)

References 120 publications

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“…Bone destruction is a major pathological factor in chronic inflammatory diseases such as AP. Various cytokines including TNF-α, IL-1α, and IL-6 were released by immunocytes to recruit the osteoclast precursors and induce the maturation of osteoclasts ( Lyu et al, 2022 ). We have detected osteoclast markers including Ctsk , Acp5 , Mmp9 , and Nfatc1 by scRNA-seq.…”

Section: Resultsmentioning

confidence: 99%

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Fan

Lyu

et al. 2023

eLife

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Oral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher levels of osteogenic related markers, including Sparc and Col1a1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the protective process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases.

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Section: Resultsmentioning

confidence: 99%

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Fan

Lyu

et al. 2023

eLife

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“…This agrees with previous studies using different cultivable or noncultivable methods. [20–22] However, Firmicutes , Proteobacteria , Actinobacteria , and Bacteroidetes were found to be prevalent in chronic apical periodontitis cases. [23,24] More specifically, the members of the genera Streptococcus , Lactobacillus , and Prevotella were highly associated with acute apical periodontitis intracanal samples.…”

Section: Discussionmentioning

confidence: 99%

Comparative oral metagenome insight into acute and chronic root canal infections

Kumari,

Dixit,

Gaur

et al. 2023

J Bio-X Res

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Background: In the dynamic progression of root canal infections, the resultant change in environmental conditions directs the adaptation of the microbiome in terms of richness, evenness, and diversity. Objective: The goal of this study is to contrast the interradicular bacterial community structures of teeth in acute and chronic stages and investigate potential microorganisms associated with persistent apical periapical infections. Methods: Interradicular samples were collected from 10 teeth in the apical periodontitis group and 10 teeth in the chronic apical periodontitis group. High-throughput next-generation sequencing (NGS)–based microbial identification through the Illumina platform was used to characterize the complex intraradicular microbial communities in acute and chronic root canal infections. Results: Bacteria were the major domain, with a prevalence of >97% (acute cases: 98.11% and chronic cases: 97.6%) compared to eukaryotes and archaea. Bacterial diversity was relatively higher in acute compared to chronic conditions under 10 and 9 phyla, 79 and 64 genera, and 172 and 135 species, respectively. These endodontically infecting bacteria belonged to Firmicutes (47.21%), Bacteroidetes (20.07%), and Proteobacteria (10.72%) in acute conditions, while in the chronic stage, Firmicutes (40.85%), Proteobacteria (27.80%), and Actinobacteria (14.79%) were abundant. The phylum Candidatus Saccharibacteria was exclusively found in acute samples. Spirochaetes and Synergistetes were found predominantly in acute infections compared to chronic infections. Bacillus and Lactobacillus were found in equal and highest abundance under the phylum Firmicutes in both conditions. Conclusion: This study provides information on the differential microbial community present in the apical root canal system of teeth with acute and chronic apical periodontitis and contributes to new approaches or channels for future research on preventive measures and therapeutic protocols during disease progression and treatment. However, functional characterization and detection of antimicrobial resistance in these two clinical conditions can supplement these findings for deciding routine drug treatment for periodontal infections.

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“…In particular, it has been reported that SCAPs may have superior osteogenic differentiation capacity compared to bone marrow mesenchymal stem cells (BMSCs) ( 10 ). Nonetheless, it was also reported that an inflammatory microenvironment could alter the hallmarks of SCAPs, leading to an inhibitory or increasing effect on osteogenic differentiation ( 11 , 12 ). Effective osteogenic differentiation of MSCs is regulated by numerous factors, including physical, chemical, and biological factors, which may stimulate different signaling pathways, transcription factors, and microRNAs (miRNAs), to direct MSCs differentiated toward osteoblast lineage ( 13 – 16 ).…”

Section: Introductionmentioning

confidence: 99%

MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis

Huang

Zheng

et al. 2023

Front. Immunol.

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IntroductionPeriapical alveolar bone loss is the common consequence of apical periodontitis (AP) caused by persistent local inflammation around the apical area. Human stem cells from apical papilla (hSCAPs) play a crucial role in the restoration of bone lesions during AP. Studies have recently identified the critical role of microRNAs (miRNAs) involved in AP pathogenesis, but little is known about their function and potential molecular mechanism, especially in the osteogenesis of hSCAPs during AP. Here, we investigated the role of clinical sample-based specific miRNAs in the osteogenesis of hSCAPs.MethodsDifferential expression of miRNAs were detected in the periapical tissues of normal and patients with AP via transcriptomic analysis, and the expression of miR-199a-5p was confirmed by qRT-PCR. Treatment of hSCAPs with miR-199a-5p mimics while loaded onto beta-tricalcium phosphate (β-TCP) ceramic particle scaffold to explore its effect on osteogenesis in vivo. RNA binding protein immunoprecipitation (RIP) and Luciferase reporter assay were conducted to identify the target gene of miR-199a-5p.ResultsThe expression of miR-199a-5p was decreased in the periapical tissues of AP patients, and miR-199a-5p mimics markedly enhanced cell proliferation and osteogenic differentiation of hSCAPs, while miR-199a-5p antagomir dramatically attenuated hSCAPs osteogenesis. Moreover, we identified and confirmed Interferon Induced Protein with Tetratricopeptide Repeats 2 (IFIT2) as a specific target of miR-199a-5p, and silencing endogenous IFIT2 expression alleviated the inhibitory effect of miR-199a-5p antagomir on the osteogenic differentiation of hSCAPs. Furthermore, miR-199a-5p mimics transfected hSCAPs loaded onto beta-tricalcium phosphate (β-TCP) scaffolds induced robust subcutaneous ectopic bone formation in vivo.DiscussionThese results strengthen our understanding of predictors and facilitators of the key AP miRNAs (miR-199a-5p) in bone lesion repair under periapical inflammatory conditions. And the regulatory networks will be instrumental in exploring the underlying mechanisms of AP and lay the foundation for future regenerative medicine based on dental mesenchymal stem cells.

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Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells

Cited by 7 publications

References 120 publications

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Comparative oral metagenome insight into acute and chronic root canal infections

MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis

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