Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells

Kuang, Yunchun; Hu, Bo; Ge, Feng; Xiang, Mingli; Deng, Yuejia; Tan, Minmin; Li, Jie; Song, Jinlin

doi:10.1007/s10522-019-09838-x

Cited by 64 publications

(57 citation statements)

References 66 publications

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“…Consequently, excessive production of H 2 O 2 caused HPDLCs to lose their differentiation potential to osteoblast and cementoblast phenotypes and reduced their levels of autophagy. These findings are similar to the results of previous studies [ 34 ] and suggest that high production of H 2 O 2 initiates pathological conditions and impairs the vitality of the PDL.…”

Section: Discussionsupporting

confidence: 92%

Phelligridin D maintains the function of periodontal ligament cells through autophagy in glucose-induced oxidative stress

Kim

Lee

et al. 2020

J Periodontal Implant Sci

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Purpose The objective of this study was to investigate whether phelligridin D could reduce glucose-induced oxidative stress, attenuate the resulting inflammatory response, and restore the function of human periodontal ligament cells (HPDLCs). Methods Primary HPDLCs were isolated from healthy human teeth and cultured. To investigate the effect of phelligridin D on glucose-induced oxidative stress, HPDLCs were treated with phelligridin D, various concentrations of glucose, and glucose oxidase. Glucose-induced oxidative stress, inflammatory molecules, osteoblast differentiation, and mineralization of the HPDLCs were measured by hydrogen peroxide (H 2 O 2 ) generation, cellular viability, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot analyses. Results Glucose-induced oxidative stress led to increased production of H 2 O 2 , with negative impacts on cellular viability, ALP activity, and calcium deposition in HPDLCs. Furthermore, HPDLCs under glucose-induced oxidative stress showed induction of inflammatory molecules (intercellular adhesion molecule-1, vascular cell adhesion protein-1, tumor necrosis factor-alpha, interleukin-1-beta) and disturbances of osteogenic differentiation (bone morphogenetic protein-2, and -7, runt-related transcription factor-2), cementogenesis (cementum protein-1), and autophagy-related molecules (autophagy related 5, light chain 3 I/II, beclin-1). Phelligridin D restored all these molecules and maintained the function of HPDLCs even under glucose-induced oxidative stress. Conclusions This study suggests that phelligridin D reduces the inflammation that results from glucose-induced oxidative stress and restores the function of HPDLCs (e.g., osteoblast differentiation) by upregulating autophagy.

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Section: Discussionsupporting

confidence: 92%

Phelligridin D maintains the function of periodontal ligament cells through autophagy in glucose-induced oxidative stress

Kim

Lee

et al. 2020

J Periodontal Implant Sci

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“…Previous reports have indicated that age-related inflammation, also referred to as inflammaging, accelerates gingival senescence in gingival tissues (33,34). The persistent presence of senescent cells can foster chronic inflammation and modify the periodontal microenvironment via changes in the levels of SASP factors (34,35). However, the precise mechanism underlying the development of inflammaging in chronic P<0.001 vs. WT; @ P<0.05, @@ P<0.01, @@@ P<0.001 vs. TLR4 KO.…”

Section: Discussionmentioning

confidence: 99%

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Qin

Chen

et al. 2020

Int J Mol Med

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Overproduction of pro-inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll-like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild-type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence-associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi-1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi-1. In addition, there was a significant reduction in the expression of Bmi-1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi-1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.

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“…The longevity effect of metformin has not yet been identified in humans, and therefore, its mechanism of action requires further investigation. Metformin regulates mitochondrial biogenesis and cellular senescence through SIRT3 [155], and decreases oxidative stress-induced senescence by activating autophagy [156].…”

Section: Metforminmentioning

confidence: 99%

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

et al. 2020

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Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.

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Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells

Cited by 64 publications

References 66 publications

Phelligridin D maintains the function of periodontal ligament cells through autophagy in glucose-induced oxidative stress

Phelligridin D maintains the function of periodontal ligament cells through autophagy in glucose-induced oxidative stress

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

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