Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging

Akkaoui, Juliet; Yamada, Chiaki; Duarte, Carolina; Ho, Anny; Vardar-Şengül, Saynur; Kawai, Toshihisa; Movila, Alexandru

doi:10.1007/s11357-020-00258-1

Cited by 31 publications

(22 citation statements)

References 47 publications

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“…Among the periodontal pathogens that have been related to this complex comorbidity conditions are A. actinomycetemcomitans, Actinomyces israelii, Capnocytophaga spp., C. pneumoniae, E. corrodens, F. nucleatum, Fusobacterium necrophorum, P. gingivalis, P. intermedia , and Streptococcus constellatus . Fusobacterium nucleatum and Fusobacterium necrophorum were indeed associated with a different, but related condition starting with pharyngitis, later developing into a full respiratory tract infection called Lemierre's syndrome (Akkaoui et al, 2020 ). Also a cross-sectional study in a student cohort reported acute sore throat associated to F. necrophorum in 20.5% of subjects and 9.4% of asymptomatic individuals.…”

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

Periodontal Inflammation and Systemic Diseases: An Overview

2021

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Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.

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Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

Periodontal Inflammation and Systemic Diseases: An Overview

2021

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“…Our previously published observations indicated that ligation of MIF and SDF-1 with CXCR4 receptor promotes OCPs chemotaxis and osteoclastogenesis in vitro as well as in the experimental model of particle-induced osteolysis using young CSF1r-eGFP-KI mice [ 10 ]. Because CSF1r-eGFP-KI mice express eGFP protein in osteoclast precursors, it was suggested that this transgenic strain could be used to elucidate the molecular mechanisms underlying chemotaxis of OCPs to osteolytic lesions in relation to aging [ 11 , 56 ]. Consequently, we examined next whether local administration of GLY could affect the recruitment of CXCR4+OCPs to PMMA particle-induced osteolysis in aged CSF1r-eGFP-KI mice by multicolor flow cytometry assay.…”

Section: Resultsmentioning

confidence: 99%

“…Although, particle-induced osteolysis is significantly elevated in patients of an advanced age, most of the published pre-clinical studies were performed using experimental models of periprosthetic bone loss induced in young mice (less than three-months old) [ 8 – 10 ]. By contrast, using CSF1r-eGFP knock in (KI) mice, whose monocyte-lineage cells predominantly express enhanced green fluorescent protein (eGFP), we recently demonstrated that the molecular mechanisms of innate responses and bone osteolysis are significantly different between young (two-month old) and aged (twenty-four-month old) mice indicating the critical need to employ experimental models of particle-induced periprosthetic osteolysis involving aged mice [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…A triterpenoid saponin glycoside glycyrrhizin (GLY), an active component of licorice plant roots ( Glycyrrhiza glabra ), possesses multiple pharmacological properties, including anti-inflammation, anti-tumor, anti-aging, and anti-oxidative activities [ 21 – 23 ] It was also suggested that GLY attenuates tissue aging and promotes cell rejuvenation via the suppression of senescence-associated secretory phenotype (SASP) markers including macrophage migration inhibitory factor (MIF) and lysosomal cathepsins [ 24 – 26 ] Besides the role of GLY in the downregulation of SASPs expression, several studies have reported that it promotes the expression of senescence-protective nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, known as sirtuins [ 27 , 28 ] It is true that the age-dependent accumulation of SASPs converts senescent cells into pro-inflammatory cells that alter osteoclastogenesis, leading to inflammatory osteolysis [ 11 , 29 , 30 ]. Furthermore, the incidence of senescent osteoclast precursors (OCPs) increases in the bone microenvironment of aging mice compared with young mice [ 31 ] and the inhibition of cellular senescence may prevent aging-related bone loss [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Glycyrrhizin mitigates inflammatory bone loss and promotes expression of senescence-protective sirtuins in an aging mouse model of periprosthetic osteolysis

Yamada

Akkaoui

et al. 2021

Biomedicine & Pharmacotherapy

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Although periprosthetic osteolysis induced by wear debris particles is significantly elevated in senior (65+ years old) patients, most of the published pre-clinical studies were performed using young (less than three-month old) mice indicating the critical need to employ experimental models of particle-induced osteolysis involving mice with advanced age. Emerging evidence indicates that currently available antiresorptive bone therapies have serious age-dependent side effects. However, a resurgence of healthcare interest has occurred in glycyrrhizin (GLY), a natural extract from the licorice roots, as alternative sources of drugs for treating inflammatory bone lytic diseases and prevention of cellular senescence. This study investigated the effects of GLY on inflammatory bone loss as well as expression patterns of senescence-associated secretory phenotype and senescence-protective markers using an experimental calvarium osteolytic model induced in aged (twenty-four-month-old) mice by polymethylmethacrylate (PMMA) particles. Our results indicate that local treatment with GLY significantly diminished the size of inflammatory osteolytic lesions in aged mice via the number of CXCR4+OCPs and Tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts. Furthermore, GLY dramatically decreased the amounts of senescence-associated secretory phenotype markers, including pro-inflammatory macrophage migration inhibitory factor (MIF) chemokine, and cathepsins B and K in the bone lesions of aged mice. By contrast, GLY significantly elevated expression patterns of senescence-protective markers, including homeostatic stromal derived factor-1 (SDF-1) chemokine, and sirtuin-1, and sirtuin-6, in the PMMA particle-induced calvarial lesions of aged mice. Collectively, these data suggest that GLY can be used for the development of novel therapies to control bone loss and tissue aging in senior patients with periprosthetic osteolysis.

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“…Although ligation of Pg-LPS and PEDHC with Toll-Like Receptor (TLR) 2 and TLR4 elicits a strong inflammatory signaling induced in young mice, various published studies indicated that TLR function may be impaired in the context of aging (16)(17)(18). Furthermore, it was also recently demonstrated that P.g-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice (19). We, however, reported that PGDHC ceramide promotes inflammation in a manner independent of TLRs (20), indicating that PGDHC may also represent a novel virulence risk factor that contributes to various age-related disorders, including periodontitis and AD.…”

Section: Introductionmentioning

confidence: 99%

Potential Role of Phosphoglycerol Dihydroceramide Produced by Periodontal Pathogen Porphyromonas gingivalis in the Pathogenesis of Alzheimer’s Disease

Yamada

Akkaoui

et al. 2020

Front. Immunol.

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BackgroundAmong different types of sphingolipids produced by human cells, the possible engagement of ceramide species in the pathogenesis of Alzheimer’s disease (AD) has attracted recent attention. While ceramides are primarily generated by de novo synthesis in mammalian cells, only a limited number of bacterial species, produce ceramides, including phosphoglycerol dihydroceramide (PGDHC) that is produced by the key periodontal pathogen Porphyromonas gingivalis. Emerging evidence indicates that virulence factors produced by P. gingivalis, such as lipopolysaccharide and gingipain, may be engaged in the initiation and/or progression of AD. However, the potential role of PGDHC in the pathogenesis of AD remains unknown. Therefore, the aim of this study was to evaluate the influence of PGDHC on hallmark findings in AD.Material and MethodsCHO-7WD10 and SH-SY-5Y cells were exposed to PGDHC and lipopolysaccharide (LPS) isolated from P. gingivalis. Soluble Aβ42 peptide, amyloid precursor protein (APP), phosphorylated tau and senescence-associated secretory phenotype (SASP) factors were quantified using ELISA and Western blot assays. ResultsOur results indicate that P. gingivalis (Pg)-derived PGDHC, but not Pg-LPS, upregulated secretion of soluble Aβ42 peptide and expression of APP in CHO-7WD10 cells. Furthermore, hyperphosphorylation of tau protein was observed in SH-SY-5Y cells in response to PGDHC lipid. In contrast, Pg-LPS had little, or no significant effect on the tau phosphorylation induced in SH-SY-5Y cells. However, both PGDHC and Pg-LPS contributed to the senescence of SH-SY5Y cells as indicated by the production of senescence-associated secretory phenotype (SASP) markers, including beta-galactosidase, cathepsin B (CtsB), and pro-inflammatory cytokines TNF-α, and IL-6. Additionally, PGDHC diminished expression of the senescence-protection marker sirtuin-1 in SH-SY-5Y cells.ConclusionsAltogether, our results indicate that P. gingivalis-derived PGDHC ceramide promotes amyloidogenesis and hyperphosphorylation, as well as the production of SASP factors. Thus, PGDHC may represent a novel class of bacterial-derived virulence factors for AD associated with periodontitis.

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Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging

Cited by 31 publications

References 47 publications

Periodontal Inflammation and Systemic Diseases: An Overview

Periodontal Inflammation and Systemic Diseases: An Overview

Glycyrrhizin mitigates inflammatory bone loss and promotes expression of senescence-protective sirtuins in an aging mouse model of periprosthetic osteolysis

Potential Role of Phosphoglycerol Dihydroceramide Produced by Periodontal Pathogen Porphyromonas gingivalis in the Pathogenesis of Alzheimer’s Disease

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