Potential Application of Human β-Defensin 4 in Dental Pulp Repair

Abstract

When pulp tissue is damaged by caries or trauma, vital pulp therapy (VPT) can help preserve the pulp tissue for long-term retention of teeth. However, the choice of pulp capping agent used in VPT is important for the successful preservation of the pulp tissue. Here we investigated the expression and biological function of human βdefensin 4 (HBD4) in dental pulp stem cells (DPSC) and explored its potential as a pulp capping agent. We examined the expression of HBD4 in DPSC in vitro using qPCR and immunofluorescence staining. We also looked at the effect of HBD4 on inflammatory factors in lipopolysaccharide (LPS)-stimulated DPSC, and its effects on mineralizing cell phenotype differentiation, via qPCR and western blot. Finally, we examined the ability of HBD4 to promote the restoration of the pulp-dentin complex in vivo, using male Wistar rats with reversible pulpitis. We found HBD4 was highly expressed in DPSC stimulated by TNF-α and IL-1α. HBD4 down-regulated the expression of inflammatory mediators (i.e., IL-1α, IL-1β, IL-6, TNF-α) in LPS-stimulated DPSC, and suppressed MAPK activity and the NF-κB pathway. HBD4 also enhanced the differentiation of DPSC into osteoblasts or odontoblasts, potentially by modulating the Notch pathway. Furthermore, HBD4 controlled the degree of pulp inflammation in a rat model of reversible pulpitis and induced the formation of restorative dentin. Together our findings indicate HBD4 may be a useful pulp capping agent for use in VPT.

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

“…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 ].…”

Dental-Derived Mesenchymal Stem Cells: State of the Art

“…To illustrate, nano-monetite hydrosol (nMH) contributed to dentin remineralization and acid resistance, but the interaction between nMH and DPSCs has not been discussed (Tan et al, 2020). Human β-defensin 4 (HBD4) controlled the intensity of dental pulp inflammation in a rat model of reversible pulpitis and induced the formation of restorative dentin (Zhai et al, 2020). For future research, studies should be conducted to reveal the interaction of DMSCs and scaffolds, and, more importantly, the underlying mechanisms in the context of tooth regeneration in vivo.…”

The multifaceted roles of antimicrobial peptides in oral diseases

“…In previous research, hBD-2 significantly (Shiba et al, 2003). hBD-4 may be useful in indirect pulp therapy because it can enhance the differentiation of stem cells into osteoblasts or odontoblasts in dental pulp (Zhai et al, 2020).…”

“…In previous research, hBD‐2 significantly increased the dentine sialophosphoprotein mRNA levels in human pulp cells, which may have the ability to stimulate odontoblast differentiation (Shiba et al., 2003). hBD‐4 may be useful in indirect pulp therapy because it can enhance the differentiation of stem cells into osteoblasts or odontoblasts in dental pulp (Zhai et al., 2020). LL37 also stimulates human pulp cell migration, odontoblastic differentiation, angiogenesis and reparative dentin formation (Horibe et al., 2018).…”