Periodontal bacterial supernatants modify differentiation, migration and inflammatory cytokine expression in human periodontal ligament stem cells

Abstract

Periodontal ligament stem cells (PDLSC) play an important role in periodontal tissue homeostasis/turnover and could be applied in cell-based periodontal regenerative therapy. Bacterial supernatants secreted from diverse periodontal bacteria induce the production of cytokines that contribute to local periodontal tissue destruction. However, little is known about the impact of whole bacterial toxins on the biological behavior of PDLSC. Therefore this study investigated whether proliferation, migration, inflammatory cytokines expression and transcriptional profile would be affected by exposure to endotoxins from bacterial species found in the subgingival plaque. PDLSC were cultured with the following bacterial supernatants: S . mutans , S . anginosus , P . intermedia , F . nucleatum , P . gingivalis and T . denticola . These supernatants were prepared in dilutions of 1:1000, 1:500, 1:300 and 1:50. Using quantitative RT-PCR, gene expression of selected inflammatory cytokines ( IL-6 , IL-8 and IL-1β ) and cell-surface receptors ( TLR2 , TLR4 ) showed upregulation of ≈2.0- to 3.0-fold, when exposed to P . intermedia , F . nucleatum , P . gingivalis and T . denticola . However, supernatants did not affect proliferation (MTT) and migration (wound scratch assays) of PDLSC. Next generation RNA sequencing confirmed modified lineage commitment of PDLSC by stimulating chondrogenesis, adipogenesis and inhibition of osteogenesis under P . gingivalis supernatant treatment compared to control. Taken together, this study shows stem cell immunomodulatory response to different periodontal bacteria supernatant and suggests that stem cell transcriptional capacity, migration/proliferation and osteogenesis may differ in the presence of those pathogens. These results bring into question stem cell contribution to periodontal tissue regeneration and onset of inflammation.

Salvianolic Acid C Attenuates LPS-Induced Inflammation and Apoptosis in Human Periodontal Ligament Stem Cells via Toll-Like Receptors 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Pathway

“…This suggests that hPDLSCs could be useful in therapy of periodontal diseases by regeneration, reconstruction, and fixation of periodontal tissue [8]. Recent studies have demonstrated that endotoxins produced by periodontal pathogens can disrupt microenvironment homeostasis and destroy periodontal tissue through suppressing the viability of hPDLSCs [4,9]. Periodontal inflammation plays important roles in progression of periodontitis, but the underlying mechanism of pathogenesis remains to be investigated.…”

“…Previous studies have demonstrated periodontitis is related to systemic conditions such as cardiovascular disease, diabetes mellitus, adverse pregnancy outcomes, and osteoporosis [3]. Periodontitis is related to immune reactions and is affected by exposure to endotoxins from Gram-negative bacterial species in the dental biofilm [4]. Currently, there are still no clinically effective therapeutic strategies for periodontitis.…”

Porphyromonas gingivalis enhances pneumococcal adhesion to human alveolar epithelial cells by increasing expression of host platelet‐activating factor receptor

“…gingivalis . Indeed, with human periodontal and immune cells, CSP stimulates pro‐inflammatory characteristics, such as induction of inflammation‐related receptor expression and pro‐inflammatory cytokine secretion [18–21], all of which contribute to the virulence of this bacterium. However, whether CSP also stimulates pro‐inflammatory characteristics with the alveolar epithelium has not been reported.…”

Current state of stem cell-based therapies: an overview

“…These cells were described as an excellent cell source owing to their ease of accessibility, their ability to differentiate into osteoblasts and odontoblasts and lack of ethical controversies (45). Moreover, dental stem cells demonstrated superior abilities in immunomodulation properties either through cell to cell interaction or via a paracrine effect (46). Stem cells of non-dental origin were also suggested for dental tissue and bone regeneration.…”