Immunization with Fimbrial Protein and Peptide Protects against Porphyromonas Gingivalis-Induced Periodontal Tissue Destruction

AbstractThe Gram-negative bacterium Porphyromonas gingivalis is a secondary colonizer of the oral biofilm and is involved in the onset and progression of periodontitis. Its fimbriae, of type-V, are important for attachment to other microorganisms in the biofilm and for adhesion to host cells. The fimbriae are assembled from five proteins encoded by the mfa1 operon, of which Mfa5 is one of the ancillary tip proteins. Here we report the X-ray structure of the N-terminal half of Mfa5, which reveals a von Willebrand factor domain and two IgG-like domains. One of the IgG-like domains is stabilized by an intramolecular isopeptide bond, which is the first such bond observed in a Gram-negative bacterium. These features make Mfa5 structurally more related to streptococcal adhesins than to the other P. gingivalis Mfa proteins. The structure reported here indicates that horizontal gene transfer has occurred among the bacteria within the oral biofilm.

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Progression of periodontal tissue destruction at splinted/non-splinted teeth. An experimental study in the dog

Journal Of Clinical Periodontology ◽

10.1111/j.1600-051x.1993.tb00693.x ◽

1993 ◽

Vol 20 (10) ◽

pp. 693-698 ◽

Cited By ~ 15

Author(s):

I. Ericsson ◽

M. Giargia ◽

J. Lindhe ◽

A.-M. Neiderud

Keyword(s):

Experimental Study ◽

Periodontal Tissue ◽

Tissue Destruction

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Microscopic spirochete counts in untreated subjects with and without periodontal tissue destruction

Journal Of Clinical Periodontology ◽

10.1111/j.1600-051x.1995.tb00140.x ◽

2005 ◽

Vol 22 (3) ◽

pp. 235-239 ◽

Cited By ~ 6

Author(s):

Bakari S. Lembariti ◽

Frans H.M. Mikx ◽

Wim H. Palenstein Helderman

Keyword(s):

Periodontal Tissue ◽

Tissue Destruction

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The potential protective immune responses to synthetic peptides containing conserved epitopes of Porphyromonas gingivalis fimbrial protein

Journal of Medical Microbiology ◽

10.1099/00222615-41-5-349 ◽

1994 ◽

Vol 41 (5) ◽

pp. 349-358 ◽

Cited By ~ 24

Author(s):

T. OGAWA

Keyword(s):

Immune Responses ◽

Porphyromonas Gingivalis ◽

Synthetic Peptides ◽

Fimbrial Protein

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Molecular Mechanism for Connective Tissue Destruction by Dipeptidyl Aminopeptidase IV Produced by the Periodontal Pathogen Porphyromonas gingivalis

Infection and Immunity ◽

10.1128/iai.73.5.2655-2664.2005 ◽

2005 ◽

Vol 73 (5) ◽

pp. 2655-2664 ◽

Cited By ~ 45

Author(s):

Yumi Kumagai ◽

Hisao Yagishita ◽

Ayako Yajima ◽

Tatsuya Okamoto ◽

Kiyoshi Konishi

Keyword(s):

Connective Tissue ◽

Molecular Mechanism ◽

Porphyromonas Gingivalis ◽

Type I Collagen ◽

Plasmid Vector ◽

Periodontal Pathogen ◽

Matrix Metalloproteinase 2 ◽

Type I ◽

Tissue Destruction ◽

Dipeptidyl Aminopeptidase

ABSTRACT Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.

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Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis

Molecular Immunology ◽

10.1016/j.molimm.2019.11.003 ◽

2020 ◽

Vol 117 ◽

pp. 110-121 ◽

Cited By ~ 4

Author(s):

Zheng Zhang ◽

Wei Yuan ◽

Junjie Deng ◽

Danyang Wang ◽

Tianyi Zhang ◽

...

Keyword(s):

Periodontal Tissue ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Tissue Destruction ◽

Experimental Periodontitis ◽

Stimulating Factor ◽

Factor G

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Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model

International Journal of Molecular Sciences ◽

10.3390/ijms21218103 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8103

Author(s):

Kyaw Thu Aung ◽

Kentaro Akiyama ◽

Masayoshi Kunitomo ◽

Aung Ye Mun ◽

Ikue Tosa ◽

...

Keyword(s):

Growth Factor Receptor ◽

Periodontal Tissue ◽

Tissue Destruction ◽

Aged Mice ◽

T Cell Apoptosis ◽

Severe Bone Loss ◽

Fas L ◽

Vitro Analysis ◽

Old Mice

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

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