Dataset Information

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model.

ABSTRACT: Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor ? (PDGFR?)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated ? galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

SUBMITTER: Aung KT

PROVIDER: S-EPMC7663404 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model.

Aung Kyaw Thu KT Akiyama Kentaro K Kunitomo Masayoshi M Mun Aung Ye AY Tosa Ikue I Nguyen Ha Thi Thu HTT Zhang Jiewen J Kohno Teisaku T Ono Mitsuaki M Hara Emilio Satoshi ES Kuboki Takuo T

International journal of molecular sciences 20201030 21

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship ...[more]

PMID: 33143068

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Project description:Introduction: Periodontitis is a chronic inflammatory oral disease that destroys soft and hard periodontal support tissues. Multiple cell death modes including apoptosis, necroptosis, pyroptosis, and ferroptosis play a crucial role in the pathogenicity of inflammatory diseases. This study aimed to identify genes associated with ferroptosis, necroptosis, and pyroptosis in different cells present in the periodontium of periodontitis patients. Methods: Gingival tissues' mRNA sequencing dataset GSE173078 of 12 healthy control and 12 periodontitis patients' and the microarray dataset GSE10334 of 63 healthy controls and 64 periodontitis patients' were obtained from Gene Expression Omnibus (GEO) database. A total of 910 differentially expressed genes (DEGs) obtained in GSE173078 were intersected with necroptosis, pyroptosis, and ferroptosis-related genes to obtain the differential genes associated with cell death (DCDEGs), and the expression levels of 21 differential genes associated with cell death were verified with dataset GSE10334. Results: Bioinformatic analysis revealed 21 differential genes associated with cell death attributed to ferroptosis, pyroptosis, and necroptosis in periodontitis patients compared with healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that 21 differential genes associated with cell death were related to various cellular and immunological pathways including inflammatory responses, necroptosis, and osteoclast differentiation. Additionally, the single-cell RNA (scRNA) sequencing data GSE171213 of 4 healthy controls and 5 periodontitis patients' periodontal tissue was analyzed to obtain cell clustering and cell types attributed to differential genes associated with cell death. We found that among 21 DCDEGs, SLC2A3, FPR2, TREM1, and IL1B were mainly upregulated in neutrophils present in the periodontium of periodontitis patients. Gene overlapping analysis revealed that IL-1B is related to necroptosis and pyroptosis, TREM1 and FPR2 are related to pyroptosis, and SLC2A3 is related to ferroptosis. Finally, we utilized the CIBERSORT algorithm to assess the association between DCDEGs and immune infiltration phenotypes, based on the gene expression profile of GSE10334. The results revealed that the upregulated SLC2A3, FPR2, TREM1, and IL1B were positively correlated with neutrophil infiltration in the periodontium. Discussion: The findings provide upregulated SLC2A3, FPR2, TREM1, and IL1B in neutrophils as a future research direction on the mode and mechanism of cell death in periodontitis and their role in disease pathogenicity.

Dataset Information

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model.

Publications

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model.

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