Transcriptome Analysis Reveals Modulation of Human Stem Cells from the Apical Papilla by Species Associated with Dental Root Canal Infection

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 14420
• Main Authors: Razghonova, Yelyzaveta, Zymovets, Valeriia, Wadelius, Philip, Rakhimova, Olena, Manoharan, Lokeshwaran, Brundin, Malin, Kelk, Peyman, Romani Vestman, Nelly
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.11.2022; MDPI
• Subjects: Bacteria; Basic Medicine; Biofilms; Bone marrow; Cbfa-1 protein; Cell and Molecular Biology; Cell Differentiation; Cell division; Cell proliferation; Cell- och molekylärbiologi; Dental pulp; Dental Pulp Cavity; dentinogenesis; Dentistry; differential gene expression analysis (DEG); Differentiation; Endodontics; Enrichment; Enterococcus faecalis; Environmental conditions; Fusobacterium nucleatum; Gene expression; Gene Expression Profiling; Genes; Genomes; Humans; Infections; Inflammation; Inflammatory response; Intracellular Signaling Peptides and Proteins - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metabolites; Microorganisms; Mineralization; odontologi; Odontology; Osteogenesis; regenerative endodontic treatment (RET); Root canals; Stem cells; Stem Cells - metabolism; stem cells from the apical papilla (SCAP); Teeth; transcriptome analysis; Transcriptomes; Transcriptomics; Transposition; Enterococcus faecalis; Fusobacterium nucleatum; regenerative endodontic treatment (RET); stem cells from the apical papilla (SCAP); dentinogenesis; osteogenesis; transcriptome analysis; differential gene expression analysis (DEG)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214420

Interaction of oral bacteria with stem cells from the apical papilla (SCAP) can negatively affect the success of regenerative endodontic treatment (RET). Through RNA-seq transcriptomic analysis, we studied the effect of the oral bacteria and , as well as their supernatants enriched by bacterial metabolites, on the osteo- and dentinogenic potential of SCAPs in vitro. We performed bulk RNA-seq, on the basis of which differential expression analysis (DEG) and gene ontology enrichment analysis (GO) were performed. DEG analysis showed that supernatant had the greatest effect on SCAPs, whereas supernatant had the least effect (Tanimoto coefficient = 0.05). GO term enrichment analysis indicated that upregulates the immune and inflammatory response of SCAPs, and suppresses cell proliferation and cell division processes. SCAP transcriptome profiles showed that under the influence of the upregulation of , , and genes occurred, which may negatively affect the SCAP's osteo- and odontogenic differentiation. downregulates the expression of and and upregulates the expression of and in SCAPs, the upregulation of which may be detrimental for SCAPs' differentiation potential. In conclusion, the present study shows that in vitro, , , and their metabolites are capable of up- or downregulating the expression of genes that are necessary for dentinogenic and osteogenic processes to varying degrees, which eventually may result in unsuccessful RET outcomes. Transposition to the clinical context merits some reservations, which should be approached with caution.