Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Under physiological conditions, matrix metalloproteinases (MMPs) are involved in the remodeling and turnover of periodontal tissue and their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). Disturbances in the balance between MMPs and TIMPs may result in excessive tissue destruction. We previously used an engineered human oral mucosa (EHOM) model to demonstrate that Porphyromonas gingivalis, a major etiological agent of periodontitis, infiltrates connective tissue and induces significant loss of attachment of the stratified epithelium from the basement membrane. The aim of the present study was to investigate the effect of P. gingivalis on the expression and production of MMP-2, MMP-9, TIMP-1, and TIMP-2 by oral fibroblasts and epithelial cells. The EHOM model was infected with P. gingivalis ATCC 33277 or its derivative gingipain-null mutant (KDP128) for different periods of time. MMP and TIMP mRNA expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) analysis, while protein secretion into the culture medium was assessed by enzyme-linked immunosorbent assays. P. gingivalis significantly up-regulated MMP-2 and MMP-9 mRNA expression by oral epithelial cells. This MMP gene activation was paralleled by TIMP-2 gene activation. However, only MMP-9 mRNA expression was significantly enhanced by the gingipain-null mutant. At 8 and 24 h post-infection, P. gingivalis increased significantly the MMP-9 protein level compared to the uninfected EHOM model. The present study reports the ability of P. gingivalis to regulate MMP and TIMP production by oral cells, a phenomenon that may contribute to tissue destruction.
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PMID:Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by Porphyromonas gingivalis in an engineered human oral mucosa model. 1722 91

The aim of this study was to investigate if coherence length is of importance in laser phototherapy. Twenty patients with moderate periodontitis were selected. After oral hygiene instructions, scaling and root planing (SRP), one side of the upper jaw was randomly selected for HeNe (632.8 nm, 3 mW) or InGaAlP (650 nm, 3 mW) laser irradiation. One week after SRP, the following parameters were measured: pocket depth, gingival index, plaque index, gingival crevicular fluid volume, matrix metalloproteinase (MMP-8), interleukin (IL-8) and subgingival microflora. The irradiation (180 s per point, energy 0.54 J) was then performed once a week for 6 weeks. At the follow up examination, all clinical parameters had improved significantly in both groups. A more pronounced decrease of clinical inflammation was observed after HeNe treatment. MMP-8 levels were considerably reduced on the HeNe side, while there was no difference for IL-8 or microflora. Coherence length appears to be an important factor in laser phototherapy.
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PMID:The importance of coherence length in laser phototherapy of gingival inflammation: a pilot study. 1733 77

Periodontitis increases the atherosclerosis risk, but information on the role of periodontal pathogens in atherogenesis is limited. In the present study we have investigated, whether the major periodontal pathogen, Aggregatibacter (Actinobacillus) actinomycetemcomitans, induces development of atherosclerosis in apolipoprotein E-deficient mice. The mice received 4, 6, or 8 weekly i.v. injections of live pathogen (10(7)CFU/50 microl/mouse) or saline as control, and were killed 1 week after the last injection. The atherosclerotic lesion formation was examined from whole aortas and aortic sinus cryosections after lipid staining. Neither the lesion area in the aortas or en face analyses, nor their immunoreactivity to the macrophage-marker CD68 differed significantly between the infected and the control mice. However, the pathogen administration increased serum C-reactive protein (CRP) concentrations, and induced proatherogenic lipoprotein profiles with smaller particle sizes in very-low density (VLDL), low density (LDL), and high density (HDL) lipoprotein fractions. It also caused elevated matrix metalloproteinase-9 expression in the aortas and increased serum gelatinase level. Lipopolysaccharide deriving from the pathogen was associated with proatherogenic lipoprotein fractions: VLDL and especially LDL. The results indicate that A. actinomycetemcomitans contributes to disturbed lipoprotein profiles, inflammatory reaction, and matrix remodelling which are known to promote the development of atherosclerosis.
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PMID:Aggregatibacter actinomycetemcomitans induces MMP-9 expression and proatherogenic lipoprotein profile in apoE-deficient mice. 1788 99

Fish oil rich in n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protects inflammation induced bone loss in chronic inflammatory diseases like rheumatoid arthritis, periodontitis, and osteoporosis. EPA and DHA differentially regulate functional parameters and gene expression in different cell types. One of the risk factors for bone loss in inflammatory bone diseases is the elevation of bone-resorbing osteoclasts and a very few studies so far have indicated that attenuation of osteoclastogenesis might be one of the mechanisms by which n-3 PUFA exert its effect on bone loss protection. However, the precise mechanism underlying this process remains unclear. Receptor activator of NF-kappaB ligand (RANKL) is known to be the most critical mediator of osteoclastogenesis. Therefore, in this study, we examined the differential effect of EPA and DHA on RANKL-stimulated osteoclastogenesis and RANKL signaling using a murine monocytic cell line RAW 264.7. DHA was found to inhibit osteoclast differentiation, activation and function more potently than EPA. The differential potential also closely correlated with the inhibition of osteoclast-specific genes like tartrate resistant acid phosphatase, cathepsin K, calcitonin receptor, matrix metalloproteinase-9 expression and osteoclast-specific transcription factor, c-Fos, as well as osteotropic proinflammatory cytokine, TNF-alpha to a greater extent with DHA than EPA. Further, pretreatment of RAW 264.7 cells with DHA also showed significantly reduced activation of NF-kappaB and p38MAPK than EPA. Our findings suggest that DHA may be much more effective than EPA in alleviating RANKL induced proinflammatory cytokine production, intracellular signaling activation, thereby decreasing osteoclast activation and bone resorption.
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PMID:Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid. 1792 47

Matrix metalloproteinases (MMPs), the key enzymes responsible for matrix degradation, are derived from polymorphonuclear leukocytes during the early stages of periodontitis. The present study determined the levels of GCF matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) and salivary MMP-8 in patients with gingivitis and periodontitis and in healthy controls. Levels of crevicular MMP-2, MMP-9 and salivary MMP-8 were determined by ELISA in subjects with healthy gingiva (n = 15), gingivitis (n = 18) and periodontitis (n = 20). Significantly higher salivary MMP-8 and crevicular MMP-9 were observed in cases of periodontitis compared to gingivitis and healthy adults. On the other hand, crevicular MMP-2 levels in periodontitis subjects were lower than those in gingivitis and healthy subjects. The three MMP levels were highly correlated to probing depth, and bleeding on probing. Salivary MMP-8, crevicular MMP- 2 and 9 may serve as biomarkers of periodontal disease and aid in early detection of periodontitis or gingivitis.
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PMID:Biomarkers of periodontitis in oral fluids. 1840 84

Periodontitis is initiated by accumulation of microbial plaque and activation of gingival inflammation through overexpression of matrix metalloproteinases (MMPs), leading to tissue destruction. Natural MMP inhibitors may be developed as therapeutic agents against periodontitis. In this study, panduratin A, a natural bioactive compound isolated from Kaempferia pandurata ROXB., was used to test its in vitro inhibitory activity against MMP-9 secretion from Porphyromonas gingivalis supernatant-induced human oral epidermoid carcinoma KB cells. Gelatin zymography, Western blot and RT-PCR analyses were performed to evaluate MMP-9 expression. The gelatin zymograms revealed that the main gelatinase secreted by P. gingivalis supernatant-induced KB cells migrated at 92 kDa, representing MMP-9. MMP-9 protein and mRNA levels were significantly decreased after panduratin A treatment (p<0.05). In contrast, panduratin A had no effect on tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 mRNA. Panduratin A also suppressed urokinase type plasminogen activator (uPA) mRNA expression. These results suggest that panduratin A could potentially prevent periodontal inflammation by decreasing the levels of MMP-9 protein and mRNA.
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PMID:Effects of panduratin A isolated from Kaempferia pandurata ROXB. on the expression of matrix metalloproteinase-9 by porphyromonas gingivalis supernatant-induced KB cells. 1912 90

Prevotella intermedia, a major periodontal pathogen, plays important roles in the initiation and development of periodontitis by stimulating the release of proinflammatory cytokines, proteinases and matrix metalloproteinases (MMPs). Our previous study demonstrated that P. intermedia induced MMP-9 expression in human periodontal ligament (hPDL) cells. In this study, we examined the effects of P. intermedia on other MMPs' expression. Semi-quantitative reverse transcriptase (RT)-PCR analysis revealed that P. intermedia ATCC 25611 supernatant increased MMP-1 and MMP-8 mRNA expression in a concentration- and time-dependent manner. Enzyme-linked immunosorbent assay and Western blot results confirmed the RT-PCR results at the protein level. Cyclooxygenase inhibitor indomethacin significantly attenuated the upregulatory effects of P. intermedia on MMP-1 and MMP-8 expression. Extracellular signal-related kinase inhibitor PD98059 and c-Jun N-terminal kinase inhibitor SP600125 considerably decreased the upregulated level of MMP-1, whereas p38 inhibitor SB203580 markedly inhibited MMP-8 expression, suggesting that prostaglandin E(2) and mitogen-activated protein kinase signaling pathways are involved in P. intermedia-induced MMP-1 and MMP-8 upregulation. Our results indicate that P. intermedia might contribute to periodontal connective tissue and bone matrix destruction through upregulating MMP production.
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PMID:Prevotella intermedia upregulates MMP-1 and MMP-8 expression in human periodontal ligament cells. 1970 69

Periodontitis (PD) and rheumatoid arthritis (RA) have been found to be clinically associated and to share the chronic nature of the inflammatory reaction associated with bone resorption activity. However, the mechanisms underlying such association are unknown. Therefore, we examined the basis of Actinobacillus actinomycetemcomitans- and Porphyromonas gingivalis-induced PD and pristane-induced arthritis (PIA) interaction in mice. Higher severity PD in the genetically inflammation prone acute inflammatory reactivity maximum (AIRmax) mice strain was associated with higher levels of TNF-alpha, IL-1beta, IL-17, matrix metalloproteinase (MMP)-13, and RANKL, whereas PD/PIA co-induction resulted in even higher levels of IL-1beta, IFN-gamma, IL-17, RANKL, and MMP-13 levels. Conversely, PD/PIA co-induction in AIRmin strain did not alter the course of both pathologies. PIA/PD co-induction resulted in altered expression of T-cell subsets transcription factors expression, with T-bet and RORgamma levels being upregulated, whereas GATA-3 levels were unaltered. Interestingly, PIA induction resulted in alveolar bone loss, such response being highly dependent on the presence of commensal oral bacteria. No differences were found in PIA severity parameters by PD co-induction. Our results show that the interaction between experimental PD and arthritis in mice involves a shared hyper-inflammatory genotype and functional interferences in innate and adaptive immune responses.
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PMID:Periodontitis and arthritis interaction in mice involves a shared hyper-inflammatory genotype and functional immunological interferences. 2042 91

Neutrophil collagenase or collagenase-2 (matrix metalloproteinase [MMP]-8) belongs to the collagenase subgroup of the MMP superfamily of calcium- and zinc-dependent neutral proteinases. MMP-8 is catalytically the most competent proteinase to initiate type I collagen and extracellular matrix degradation associated with periodontal and peri-implant tissue destruction leading to tooth and dental implant loss. Regarding cardiovascular diseases, pathologically excessive MMP-8 has been implicated in atherosclerotic plaque destabilization and rupture probably through its proteolytic ability to thin the protecting collagenous fibrous cap lining coronary and other arteries. During the initiation and course of inflammatory responses in periodontitis, peri-implantitis and cardiovascular diseases, proinflammatory mediators including especially MMP-8 are up-regulated not only in affected tissues but also in the secreted, disease-affected, oral fluids (gingival crevicular fluid [GCF], peri-implant sulcular fluid [PISF], mouthrinse and saliva) as well as in serum and plasma. Regarding periodontitis, peri-implantitis and cardiovascular diseases, the oral fluid and serum MMP-8 analysis has proven to be a sensitive and an objective biomarker as an indicator of health, pathologic processes and pharmacologic response to therapeutic intervention including doxycycline medication as an MMP inhibitor. Oral fluids, i.e., GCF, PISF, mouthrinse and saliva are easily and non-invasively collected for the site- and patient-specific diagnostic analysis in periodontitis and peri-implantitis, whereas serum and/or plasma sample collection is required for diagnosis and monitoring of cardiovascular diseases. Research in periodontology and cardiology has identified a need for the development of innovative point-of-care diagnostic tests for MMP-8. We summarize and review the recent studies on these topics.
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PMID:Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines. 2093 84

Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)-induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor-kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs.
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PMID:Active principles of Grindelia robusta exert antiinflammatory properties in a macrophage model. 2103 29


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