UMLS:C0031099 - FACTA Search

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Query: UMLS:C0031099 (periodontitis)
12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagenolysis in periodontitis is thought to be modulated by the expression of three genes, collagenase, tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2). We assessed the possible difference in TIMP-1, TIMP-2 and collagenase mRNA levels between gingival samples from patients with periodontitis and those from healthy subjects by reverse transcription-polymerase chain reaction (RT-PCR). This technique allows detection of transcripts from a very small sample quantity. The experiments showed that levels of TIMP-1 and collagenase transcripts relative to beta-actin are significantly higher in the diseased group than in healthy controls (8.11 +/- 0.83 versus 1.38 +/- 0.28% for TIMP-1 and 0.50 +/- 0.10 versus 0.0075 +/- 0.0024% for collagenase, respectively). The difference in TIMP-2 between the two groups (2.91 +/- 0.46 versus 1.84 +/- 0.87%) did not differ. Therefore, the host would have responded to the increase in collagenase level by preferentially producing TIMP-1 against tissue destruction. The differential gene expression of TIMP-1 and TIMP-2 in our study may account for a distinct genetic regulation of TIMP-1 and -2 in vivo.
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PMID:Expression of TIMP-1, TIMP-2 and collagenase mRNA in periodontitis-affected human gingival tissue. 841 Jun

Tetracyclines (TCs) have wide therapeutic usage as antimicrobial agents; these drugs (e.g., minocycline, doxycycline) remain useful as adjuncts in periodontal therapy. However, TCs also have non-antimicrobial properties which appear to modulate host response. In that regard, TCs and their chemically-modified analogs (CMTs) have been shown to inhibit the activity of the matrix metalloproteinase (MMP), collagenase. The activity of this enzyme appears crucial in the destruction of the major structural protein of connective tissues, collagen. Such pathologic collagenolysis may be a common denominator in tissue destructive diseases such as rheumatoid and osteoarthritis, diabetes mellitus, bullous dermatologic diseases, corneal ulcers, and periodontitis. The mechanisms by which TCs affect and, possibly, diminish bone resorption (a key event in the pathogenesis of periodontal and other diseases) are not yet understood. However, a number of possibilities remain open for investigation including the following: TCs may 1) directly inhibit the activity of extracellular collagenase and other MMPs such as gelatinase; 2) prevent the activation of its proenzyme by scavenging reactive oxygen species generated by other cell types (e.g. PMNs, osteoclasts); 3) inhibit the secretion of other collagenolytic enzymes (i.e. lysosomal cathepsins); and 4) directly affect other aspects of osteoclast structure and function. Several recent studies have also addressed the therapeutic potential of TCs and CMTs in periodontal disease. These drugs reduced excessive gingival collagenase activity and severity of periodontal breakdown in rats infected with Porphyromonas gingivalis and in diabetic rats. Furthermore, the latter drug (CMT) was not associated with the emergence of TC-resistant microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blocking periodontal disease progression by inhibiting tissue-destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs. 841 Jun 21

Tetracyclines have recently been shown to inhibit the activity of some but not all mammalian matrix metalloproteinases believed to mediate periodontal destruction. However, the specificity of this effect, which could have significant therapeutic implications for different periodontal diseases, has not been examined in detail. Doxycycline and 4-de-dimethylaminotetracycline (CMT-1) have been tested in vitro for their ability to inhibit human neutrophil and fibroblast interstitial collagenases and collagenase in human gingival crevicular fluid (GCF). The GCF samples were obtained from systemically healthy and insulin-dependent diabetic adult periodontitis patients and from localized juvenile periodontitis (LJP) patients. The concentrations of these 2 tetracyclines required to inhibit 50% of the collagenase activity (IC50) were found to be 15 to 30 microM for human neutrophil collagenase and for collagenase in GCF of systemically healthy and diabetic adult periodontitis patients. These concentrations approximate the tetracycline levels observed in vivo during treatment with these drugs. In contrast, human fibroblast collagenase and GCF collagenase from LJP patients were both relatively resistant to tetracycline inhibition; the IC50 for doxycycline and CMT-1 for these 2 sources of collagenase were 280 and 500 microM, respectively. Based on these and other findings, we propose the following: 1) that systemic levels of tetracycline may inhibit connective tissue breakdown by inhibiting neutrophil collagenase; 2) that tetracyclines do not inhibit fibroblast-type collagenase, which may help explain their lack of effect on normal connective tissue remodeling; 3) that tetracycline inhibition of collagenases may serve to identify the cellular origin of the enzyme; and 4) that tetracyclines can also prevent the oxidative activation of latent human procollagenases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracycline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article. 843 57

The last 25 years have brought unprecedented advances to our understanding of periodontal disease. Consider that in 1970 periodontitis was believed to effect most individuals over the age of 35 years, to progress steadily in an individual once initiated until teeth were lost, to be the primary cause of tooth loss in adults, to be caused by the bacterial mass accumulating on the tooth surface and subgingivally, and to involve the host in some fashion or another. In the 25 years since then, impressive research advances in the epidemiology of periodontal disease, the specific bacterial etiology of periodontal disease and the immunoinflammatory mediators of periodontal tissue destruction have greatly altered our view of periodontal disease. Thus, given these research advances in the understanding of periodontitis, what may the future hold for improved diagnosis and treatment of periodontal disease? Impressive research into new ways to diagnose the periodontal diseases is well underway. Investigators are seeking new ways to diagnose an individual's degree of risk for periodontal disease initiation, susceptibility to disease progression, level of disease "activity" and the likely response to treatment and recurrence of active disease. New diagnostic tests should greatly advance our ability to more accurately and specifically diagnose periodontal disease. The future also looks promising for new treatment strategies to slow or arrest periodontal disease progression. The bacterial specificity of periodontal disease etiology revealed since 1970 has logically led to the use of antibiotics in periodontitis treatment. In the late 1980s the concept of locally delivering antibiotics to the periodontal pocket was introduced, and subsequent clinical trials have indicated that it is possible to reduce pocket depth and inflammation with tetracycline locally delivered to the periodontal pocket. Likely, we have barely scratched the surface in studying the efficacy of locally delivery antimicrobial agents to alter the progression of periodontal disease. As new agents are developed and better delivery systems to the periodontal pocket are developed, the future should see a variety of antimicrobial agents available which can slow periodontal disease progression. The future also holds promise for slowing periodontal disease progression by blocking inflammatory pathways important in periodontal tissue destruction. Clinical trials of flubiprofen, naproxen and ketoprofen indicate that it is possible to slow periodontal disease progression with non-steroidal anti-inflammatory drugs which inhibit one destructive pathway. In addition, data from animal models indicate that chemically modified tetracycline as an inhibitor of collagenase can slow disease progression in animals. Again, we have likely only just begun to explore the wide range of molecular mediators of tissue destruction which may be targeted for blocking and thereby slow or arrest periodontal disease progression. Last, research into regenerating periodontal structures lost as a result of disease has had a noteworthy record of progress in the past 25 years. Techniques that utilize bone grafts, root treatments, tissue guiding membranes or polypeptide growth factors have ably indicated that it is possible to regenerate new attachment structures in humans. As investigators continue to unravel the mysteries of the embryonic development of the periodontium, the ability to predictably regenerate lost periodontal attachment structures holds great promise for the future.
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PMID:The impact of new technologies to diagnose and treat periodontal disease. A look to the future. 870 94

Specially-formulated low-dose doxycycline (LDD) regimens have been found to reduce collagenase activity in the gingival tissues and crevicular fluid (GCF) of adult periodontitis subjects in short-term studies. In the current, double-blind, placebo-controlled study, adult periodontitis patients were administered for 6 months a "cyclical" regimen of either LDD or placebo capsules; and various clinical parameters of periodontal disease severity, and both collagenase activity and degradation of the serum protein, alpha 1-PI, in the GCF were measured at different time periods. No significant differences between the LDD- and placebo-treated groups were observed for plaque index and gingival index. However, attachment levels, probing depth, and GCF collagenase activity and alpha 1-PI degradation were all beneficially and significantly (P < 0.05) affected by the drug regimen. We propose: 1) that LDD inhibits tissue destruction in the absence of either antimicrobial or significant anti-inflammatory efficacy; and 2) that long-term LDD could be a useful adjunct to instrumentation therapy in the management of the adult periodontitis patient.
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PMID:The "cyclic" regimen of low-dose doxycycline for adult periodontitis: a preliminary study. 872 9

It is known that the host responds to an increased concentration of collagenase [or matrix metalloproteinase (MMP)-1] by preferentially expressing mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1) in order to overcome tissue destruction due to periodontitis. To further elucidate the relation between MMPs and TIMPs in periodontitis-affected tissues, the expression of mRNA for MMP-1, -3 and -8, and TIMP-1 and -2, in 10 gingival samples from patients and five from healthy individuals was assessed by reverse transcription-polymerase chain reaction. The diseased group showed significantly higher levels of MMP-1, -3, -8 and TIMP-1 mRNA relative to beta-actin than the control group (mean +/- SE: diseased vs healthy (%): 0.26 +/- 0.05 vs 0.018 +/- 0.0040 for MMP-1; 0.09 +/- 0.16 vs 0.063 +/- 0.016 for MMP-3; 0.068 +/- 0.017 vs 0.006 +/- 0.0010 for MMP-8; 12.66 +/- 2.90 vs 2.71 +/- 0.54 for TIMP-1; p < 0.01). TIMP-2 did not significantly differ between the two groups (1.79 +/- 0.33 vs 1.42 +/- 0.53; p > 0.05). The preferential increase in the level of MMP-3 mRNA relative to that of MMP-1 and -8 in inflamed gingiva would be relevant to tissue destruction because MMP-3 is a broad-spectrum MMP and a pivotal activator of latent MMP-1 and -8. Therefore, the overall increase in MMP-1, -3 and -8 mRNA in periodontitis-affected gingiva might account for a concerted action of MMPs during connective tissue destruction in periodontitis.
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PMID:Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue. 873 11

Sections of tissue biopsies obtained from advanced, destructive periodontitis were compared with minimally inflamed periodontal tissues in relation to the distribution of type I (interstitial) collagenase. Immunohistochemistry using a highly specific antiserum showed weak staining of occasional vessels in minimally inflamed specimens but widespread reactivity, localized to the vasculature, in advanced disease. In situ hybridization confirmed the vascular source of type I collagenase. Minimally inflamed tissues did not react with antibody to urokinase-type plasminogen activator, a potential activator of pro-collagenase, but there was a consistent strong reaction in advanced disease. Antibody to tissue inhibitor of metalloproteinase (TIMP)-1 did not react with minimally inflamed tissues, but gave intense, widespread vascular staining in advanced disease, whereas antibody to TIMP-2 produced localized connective tissue staining. These results indicate that upregulation of proteinases and inhibitors related to the vasculature is an integral component of destructive periodontitis.
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PMID:Vascular co-localization of proteolytic enzymes and proteinase inhibitors in advanced periodontitis. 877 91

The proteolytic erosion of the temporal bone is the key event in the pathognomonic course of cholesteatoma progression. The molecular mechanisms of bone resorption, endangering the ossicles, the inner ear, the facial nerve, large vessels or the brain, are not understood. Recently, a new family of proteolytic enzymes, the matrix-metalloproteinases (MMP's) has been described and identified, which seems to play a pivotal role in matrix- and bone homeostasis and inflammatory osteolytic diseases, e.g. osteoarthritis and periodontitis. These enzymes are sophisticatedly controlled by specific inhibitors and activation cascades. We investigated whether human cholesteatoma tissue expresses MMP's and MMP-inhibitors. By immunocytochemistry of cholesteatoma-cryosections, the expression of MMP-2 (72 kD collagenase), MMP-9 (92 kD collagenase), and MMP-3 (stromelysin-1) could be seen to be strictly confined to the basal and suprabasal cell layer of the cholesteatoma epithelium. The neutrophil collagenase (MMP-8) showed a more disseminated expression in the epithelium and the granulation tissue as well. The tissue inhibitor of metalloproteases, TIMP-1, could be detected only in very limited areas of the granulation tissue in a quite randomized manner. Therefore, a derailment in favor of proteolysis of the normally tightly controlled MMP-system might be postulated. The results indicate that members of the MMP-family could play an active role in the molecular mechanisms of cholesteatoma invasion into the temporal bone. This offers new insights into the pathophysiology of the disease and of potential therapeutic approaches.
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PMID:Expression of matrix-metalloproteinases and their inhibitors in human cholesteatomas. 879 Jul 47

During earlier examination of interleukin-1 (IL-1)-induced matrix metalloproteinase gene expression in human gingival fibroblasts a highly induced immediate early gene, I kappa B-alpha, a NF kappa B DNA-binding inhibitor, was identified. The aim now was to investigate whether recombinant (r)IL-1 beta induces the stimulation of NF kappa B and its inhibitor proteins in human gingival fibroblasts and to understand if inhibition of its activity affects collagenase gene expression. Primary gingival fibroblasts (human) were treated with rIL-1 beta to determine the effect on NF kappa B-like DNA-binding activity. IL-1 induced the production of steady-state mRNA levels of I kappa B-alpha in the cultured fibroblasts. Nuclear run-on transcription studies demonstrated that rIL-1 induction of I kappa B-alpha may be transcriptionally regulated. Using electrophoretic mobility gel-shift assays it was shown that rIL-1 activates NF kappa B-like, DNA-binding activity in these fibroblasts. NF kappa B-like DNA-binding activity was rapidly induced and turned over in gingival fibroblasts with peak activity at 30 min after rIL-1 treatment. Further, treatment with chymotrypsin protease inhibitor and antioxidant inhibitor prevented IL-1-induced, NF kappa B-like, DNA-binding activity and collagenase mRNA production. When coupled with the existence of NF kappa B consensus DNA-binding sites on the collagenase gene promoter, these findings suggest that the stimulation of NF kappa B in gingival fibroblasts by rIL-1 could play an important part in the regulation of their collagenase gene expression. The ability of IL-1 to stimulate this expression may define a pivotal role for this cytokine in the pathogenesis of periodontitis.
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PMID:Association of interleukin-1-induced, NF kappa B DNA-binding activity with collagenase gene expression in human gingival fibroblasts. 880 9

Previous observations suggest that interleukin-1 (IL-1) may play an important role in the progression of periodontitis. In the present study, we investigated whether a cell-associated IL-1 alpha (CAIL-1 alpha) produced in human gingival fibroblasts (HGF) induces biological activities related to the progression of periodontitis. HGF were treated with recombinant human IL-1 beta (rhIL-1 beta) for 12 h. After that, the cell layers of HGF were washed 3 times with fresh medium and were then fixed with 1% paraformaldehyde. The fixed cell layers of HGF were used for assays for bone resorbing activity, prostaglandin E2 (PGE2) production and collagenase activity. Fixed cell layers of HGF treated with rhIL-1 beta enhanced not only calcium release from BALB/c mouse calvaria but also PGE2 production and collagenase activity in HGF and human periodontal ligament fibroblasts (HPLF) cultured on the fixed cell layers. These activities were neutralized by treatment with monoclonal mouse anti-human IL-1 alpha antibody, but monoclonal mouse anti-human IL-1 beta antibody showed no effects on these activities. The induction of these activities by fixed cell layers of HGF required direct contact between the fixed cell layers and the calvaria, HGF, or HPLF. These results suggest that CAIL-1 alpha produced in HGF treated with rhIL-1 beta induces bone resorbing activity, PGE2 production and collagenase activity in the target cells by direct contact; CAIL-1 alpha may play an important role in the progression of periodontitis.
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PMID:Interleukin-1 alpha produced in human gingival fibroblasts induces several activities related to the progression of periodontitis by direct contact. 885 40

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