Visfatin Induces Senescence of Human Dental Pulp Cells

Abstract

Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin, is closely associated with cellular senescence. However, little is known about the effect of visfatin on the senescence of human dental pulp cells (hDPCs). Here, it was found that in vivo visfatin levels in human dental pulp tissues increase with age and are upregulated in vitro in hDPCs during premature senescence activated by H2O2, suggesting a correlation between visfatin and senescence. In addition, visfatin knockdown by small interfering RNA led to the reduction in hDPC senescence; however, treatment with exogenous visfatin protein induced the senescence of hDPCs along with increased NADPH consumption, which was reversed by FK866, a chemical inhibitor of visfatin. Furthermore, visfatin-induced senescence was associated with both the induction of telomere damage and the upregulation of senescence-associated secretory phenotype (SASP) factors as well as NF-κB activation, which were all inhibited by FK866. Taken together, these results demonstrate, for the first time, that visfatin plays a pivotal role in hDPC senescence in association with telomere dysfunction and the induction of SASP factors.

Aging and Senescence of Dental Pulp and Hard Tissues of the Tooth

“…Additionally, it was recently elucidated that visfatin, a type of adipokine, increases in senescent HDPCs; exogenous visfatin induces HDPC aging along with upregulation of SASP factors, whereas the chemical inhibitor of visfatin, FK866, reduces senescent features in HDPCs ( Figure 2B; Ok et al, 2020). Another group reported that miR-433, which is increased in aged HDPCs, is a senescence-associated miRNA of HDPCs that targets GRB2 ( Figure 2B; Wang et al, 2015).…”

Dental follicle stem cells rescue the regenerative capacity of inflamed rat dental pulp through a paracrine pathway

“…When exposed to bacteria and/or their toxic components, DPCs can recognize invading bacteria via their expression of a variety of pattern recognition receptors [1,[19][20][21] and induce an innate immune response by expressing antimicrobial peptides (AMPs) and secreting various inflammatory cytokines, such as TNF-α, IL-6, IL-8, IL-1α, CCL7, CCL26, and CXCL11 [19,[22][23][24][25][26], and these effects lead to the recruitment of macrophages, neutrophils, and other immune cells and initiation of the early inflammatory response to eliminate invading microbes [1]. Moreover, DPCs subsequently migrate to the injured site, where they differentiate into odontoblast-like cells to synthesize reparative dentin, initiating repair and regeneration [27][28][29][30]. However, antibacterial activities easily induce the inflammatory cascade and thereby propagate sustained inflammation [2][3][4], which not only irreversibly damages vital pulp tissue but also actively impedes the repair responses of DPCs, and these effects eventually lead to total necrosis of the pulp [1,24].…”

Oral Senescence: From Molecular Biology to Clinical Research

“…The oral cavity is the site of trauma, is susceptible to toxin and drug exposure, responds to the impact of systemic disease and aging and is exposed to microbial infection. Whilst senescence has been implicated in the pathobiology of odontogenesis (79)(80)(81), changes in the supporting structures of the teeth (82,83), the pathology of salivary glands (84) and disruption of homeostasis in the oral mucosa, it is thought to play a fundamental role in the most prevalent human disorder, namely periodontal disease (82). It has been proposed that Gram-negative bacterial infection leads to a DNA damage response in both gingival keratinocytes and fibroblasts, chronic inflammation results in ROS-mediated oxidative DNA damage and keratinocyte senescence leads to breakdown of the cervical epithelial barrier (62).…”