Periodontitis is a bacterium-induced chronic inflammation that destroys tissues that attach teeth to jaw bone. Pathologically excessive matrix metalloproteinase 8 (MMP-8) is among the key players in periodontal destruction by initiating type I collagen degradation. We studied MMP-8 in Porphyromonas gingivalis-induced periodontitis by using MMP-8-deficient (MMP8 ؊/؊ ) and wild-type (WT) mice. Alveolar bone loss, inflammatory mediator expression, serum immunoglobulin, and lipoprotein responses were investigated to clarify the role of MMP-8 in periodontitis and systemic inflammatory responses. P. gingivalis infection induced accelerated site-specific alveolar bone loss in both MMP8؊/؊ and WT mice relative to uninfected mice. The most extensive bone degradation took place in the P. gingivalis-infected MMP8 ؊/؊ group. Surprisingly, MMP-8 significantly attenuated (P < 0.05) P. gingivalis-induced site-specific alveolar bone loss. Increased alveolar bone loss in P. gingivalis-infected MMP8 ؊/؊ and WT mice was associated with increase in gingival neutrophil elastase production. Serum lipoprotein analysis demonstrated changes in the distribution of high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) particles; unlike the WT mice, the MMP8 ؊/؊ mice underwent a shift toward a smaller HDL/VLDL particle sizes. P. gingivalis infection increased the HDL/VLDL particle size in the MMP8 ؊/؊ mice, which is an indicator of lipoprotein responses during systemic inflammation. Serum total lipopolysaccharide activity and the immunoglobulin G-class antibody level in response to P. gingivalis were significantly elevated in both infected mice groups. Thus, MMP-8 appears to act in a protective manner inhibiting the development of bacterium-induced periodontal tissue destruction, possibly through the processing anti-inflammatory cytokines and chemokines. Bacterium-induced periodontitis, especially in MMP8 ؊/؊ mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.
Peri-implantitis PISF contained higher collagenase-2 levels and activity than GCF from similar deep CP sites. GCF and PISF from severe CP and PI exhibited the highest activation of MMP-8 isoenzymes species (PMN and fibroblast-type).
f Chronic biofilm infections are often accompanied by a chronic inflammatory response, leading to impaired healing and increased, irreversible damage to host tissues. Biofilm formation is a major virulence factor for Candida albicans and a challenge for treatment. Most current antifungals have proved ineffective in eradicating infections attributed to biofilms. The biofilm structure protects Candida species against antifungals and provides a way for them to evade host immune systems. This leads to a very distinct inflammatory response compared to that seen in planktonic infections. Previously, we showed the superior efficacy of DL-2-hydroxyisocaproic acid (HICA) against various bacteria and fungi. However, the immunomodulatory properties of HICA have not been studied. Our aim was to investigate the potential anti-inflammatory response to HICA in vivo. We hypothesized that HICA reduces the levels of immune mediators and attenuates the inflammatory response. In a murine model, a robust biofilm was formed for 5 days in a diffusion chamber implanted underneath mouse skin. The biofilm was treated for 12 h with HICA, while caspofungin and phosphate-buffered saline (PBS) were used as controls. The pathophysiology and immunoexpression in the tissues surrounding the chamber were determined by immunohistochemistry. Histopathological examination showed an attenuated inflammatory response together with reduced expression of matrix metalloproteinase 9 (MMP-9) and myeloperoxidase (MPO) compared to those of chambers containing caspofungin and PBS. Interestingly, the expression of developmental endothelial locus 1 (Del-1), an antagonist of neutrophil extravasation, increased after treatment with HICA. Considering its anti-inflammatory and antimicrobial activity, HICA may have enormous therapeutic potential in the treatment of chronic biofilm infections and inflammation, such as those seen with chronic wounds.
The present study demonstrated the presence of soluble or shed forms of MMP-25 and MMP-26 in GCF of patients with different periodontal diseases. Increased levels and activation of MMP-25 and MMP-26 in GCF are associated with an enhanced severity of periodontal inflammation, suggesting that these novel MMPs can participate in the progression of periodontal diseases. They may prove to be diagnostically useful and could be targets of medication in the future.
We investigated whether certain Actinobacillus actinomycetemcomitans clones occur in elevated proportions in subgingival flora, and if the proportions relate to other bacteria in the samples. A total of 121 A. actinomycetemcomitans strains from 121 patients with periodontitis were serotyped and 60 strains were also genotyped. The 121 strains were divided into three groups and the 60 strains into two groups according proportion of A. actinomycetemcomitans. The samples from the 60 patients with genotyped strains were cultured for five other species. Among the 121 strains, serotype b occurred significantly more frequently in the high- (n = 14, proportions > 5%, mean = 18.09, SD = 20.07%) than low- (n = 49, proportions < or = 0.1%), mean = 0.04, SD = 0.03%) or intermediate-proportion groups (n = 58, proportions > 0.5%, mean = 1.31, SD = 1.24%). Genotype 3 occurred significantly more frequently in samples with low A. actinomycetemcomitans proportions (n = 28, < or = 0.1%, mean = 0.04, SD = 0.03%) than in those with high proportions (n = 32, > 0.1%, mean = 5.70, SD = 14.60%). No differences were seen in the detection frequencies or proportions of the five bacterial species between the samples with low or high A. actinomycetemcomitans proportions. The results indicate that certain clonotypes of A. actinomycetemcomitans may preferentially occur as low proportions, suggesting their controlled growth. Conversely, some serotype b clones may have a competitive advantage in subgingival flora.
Periodontal diseases that affect the marginal and apical periodontium result from the interaction between bacterial biofilm and the host response. Oral fluid biomarkers might aid clinical diagnosis. Matrix metalloproteinases (MMPs) are a family of 24 proteases that act in physiological and pathological conditions. They can degrade almost all extracellular matrix constituents and regulate inflammatory processes. They are mainly inhibited by tissue inhibitors of metalloproteinases. The aim of this study was to perform a current literature review with a special reference on the diagnostic and clinical utility of oral fluid MMPs, especially MMP-8, and their inhibitors in periodontal and oral diseases. MMP-8 is the main collagenolytic MMP detected in oral fluids, such as saliva, oral mouthrinse, gingival crevicular fluid, and peri-implant fluid. MMP-8, and potentially MMP-9, in oral fluids represent strong biomarker candidates associated especially with periodontal disease diagnosis, severity, progression, and follow-up. Additionally, they show diagnostic potential for systemic conditions, such as pregnancy, myocardial infarction, and smoking. A commercially available mouthrinse, active MMP-8 chair-side/ point-of-care lateral flow immunoassay, shows enough sensitivity and specificity to detect clinical signs of periodontitis. The current literature supports that high MMP-8 levels reflect the loss of periodontal supporting tissues rather than inflammation, representing a potentially useful sidediagnostic point-of-care oral disease biomarker, especially in periodontal diseases.
Increased GCF laminin-5 gamma2-chain fragments in periodontitis sites with deep periodontal pocket suggest that these cleaved 40 and 70 kDa fragments could reflect the extent of the inflammatory reaction in CP.
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