MicroRNA-506 Is Involved in Regulation of the Occurrence of Lipopolysaccharides (LPS)-Induced Pulpitis by Sirtuin 1 (SIRT1)

Abstract

Departmental sources Background: Toothache often occurs with pulpitis. Lipopolysaccharide (LPS) is produced by gram-negative bacteria, and its accumulation is related to clinical symptoms of pain. MicroRNAs (miRNAs) display anti-inflammatory potential due to their direct regulation of cellular protein expression, which can promote inflammatory changes in dental pulp tissues. However, the mechanism of LPS-induced pulpitis is still unclear. Material/Methods: In this study, dental pulp stem cells (DPSCs) were separated and cultured from rat dental pulp tissues; then, LPS was administered to induce inflammation and activate the TLR4 pathway. Results: It was found that miR-506 was upregulated following LPS treatment in DPSCs. The inhibition of miR-506 in LPS-treated DPSCs led to attenuated inflammation and deactivation of the TLR4 pathway. Furthermore, the bioinformatic analysis and dual-luciferase reporter gene assay indicated that miR-506 could target the 3'-UTR of sirtuin 1 (SIRT1). Additionally, SIRT1 decreased in LPS-treated DPSCs, and miR-506 transfection resulted in SIRT1 upregulation. SIRT1 overexpression showed a similar inhibitory effect as that of miR-506 downregulation on inflammation and TLR4 activation in DPSCs. Conclusions: In brief, miR-506 can protect dental pulp in LPS-induced inflammation by inhibiting the SIRT1-mediated TLR4 pathway.

The Role of microRNAs in Pulp Inflammation

“…Furthermore, studies have reported that miR-506 is associated with the inflammatory response, since its overexpression is capable of activating the immune system [91], favoring the development of various inflammatory diseases [92]. The function of miR-506 in pulp inflammation is not well-known, however, a study carried out by Wang et al coincides with that previously reported in the literature, since in this study, it was observed that in DPSCs stimulated with LPS, the expression of miR-506 was upregulated, activating the TLR-4 signaling pathway by upregulating sirtuin (SIRT)-1, together with an increase in the expression of pro-inflammatory proteins, such as IL-1β, IL-6, and TNF-α [93]. These findings suggest a pro-inflammatory role for miR-506 [94]; however, more studies are needed to understand the role of miR-506 in the pathogenesis of pulp disease.…”

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

“…miR-223-3p may play a role in promoting the angiogenesis of HUVECs [ 121 ]. A higher expression of miR-506 and downregulation of Sirtuin 1 (SIRT1) are observed in LPS-induced hDPCs—a finding closely associated with activation of the TLR4-NFkB pathway and expression of pro-inflammatory cytokines: IL-1β, IL-6, and TNF-a [ 122 ]. Human β-Defensin 4 (HBD4) exerts anti-inflammatory effects in vitro and promotes the mineralization of DPSC [ 123 ].…”

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…In the LPS-treated DPSCs, the expression of miR-506 is upregulated, and TLR-4 pathway is activated. However, miR-506 knockdown attenuates the inflammatory response and suppresses the TLR-4 pathway by upregulating SIRT1 [ 166 ]. These inflammatory responses are reversed in the presence of let-7c-5p overexpression in LPS-induced DPSCs.…”