27 results on '"Sorsa, T."'
Search Results
2. Regulation of PGLYRP1 and TREM-1 during Progression and Resolution of Gingival Inflammation.
- Author
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Silbereisen, A., Hallak, A.K., Nascimento, G.G., Sorsa, T., Belibasakis, G.N., Lopez, R., and Bostanci, N.
- Published
- 2019
- Full Text
- View/download PDF
3. Doxycycline effects on serum bone biomarkers in post-menopausal women.
- Author
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Golub LM, Lee HM, Stoner JA, Reinhardt RA, Sorsa T, Goren AD, Payne JB, Golub, L M, Lee, H-M, Stoner, J A, Reinhardt, R A, Sorsa, T, Goren, A D, and Payne, J B
- Abstract
We previously demonstrated that subantimicrobial-dose-doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two-year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
4. Host-Pathogen Interactions in Progressive Chronic Periodontitis.
- Author
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Hernández, M., Dutzan, N., García-Sesnich, J., Abusleme, L., Dezerega, A., Silva, N., González, F.E., Vernal, R., Sorsa, T., and Gamonal, J.
- Subjects
PERIODONTITIS ,CHRONIC diseases ,IMMUNE response ,CYTOKINES ,ALVEOLAR process ,PERIODONTIUM ,PRECANCEROUS conditions ,BACTERIA ,METALLOPROTEINASES - Abstract
Periodontitis is an infection characterized by the occurrence of supporting tissue destruction with an episodic nature. Disease progression is often determined by the loss of attachment level or alveolar bone, and sequential probing of periodontal attachment remains the most commonly utilized method to diagnose progressive destruction of the periodontium. The tolerance method has been the most extensive clinical method used in recent years to determine site-specific attachment level changes. There is abundant evidence that major tissue destruction in periodontal lesions results from the recruitment of immune cells. Considerable effort has been made to study the host cell and mediator profiles involved in the pathogenesis of chronic periodontitis, but the definition of active sites, where current periodontal breakdown occurs, and consecutive characterization of the mediators involved are still among the main concerns. In the present review, we summarize periodontopathic bacteria and host factors, including infiltrating cell populations, cytokines, and host matrix metalloproteinases, associated with under-going episodic attachment loss that could partly explain the mechanisms involved in destruction of the supporting tissues of the tooth. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
- Full Text
- View/download PDF
5. Doxycycline Effects on Serum Bone Biomarkers in Postmenopausal Women.
- Author
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Golub, L. M., Lee, H.-M., Stoner, J. A., Reinhardt, R. A., Sorsa, T., Goren, A. D., and Payne, J. B.
- Subjects
TETRACYCLINES ,BONE resorption inhibitors ,POSTMENOPAUSE ,PERIODONTITIS ,OSTEOPENIA ,BIOMARKERS - Abstract
We previously demonstrated that subantimicrobialdose- doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two-year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
6. MMPs, IL-1, and TNF are Regulated by IL-17 in Periodontitis.
- Author
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Beklen, A., Ainola, M., Hukkanen, M., Gürgan, C., Sorsa, T., and Konttinen, Y. T.
- Subjects
IMMUNOCYTOCHEMISTRY ,PERIODONTITIS ,METALLOPROTEINASES ,INTERLEUKIN-1 ,TUMOR necrosis factors ,CYTOKINES ,MACROPHAGES - Abstract
Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1β and tumor necrosis factor-alpha (TNF-α), it was hypothesized that it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1β, TNF-α, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1β and TNF-α, but it induced IL-1β and TNF-α production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
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7. Gingival Tissue and Crevicular Fluid Co-operation in Adult Periodontitis.
- Author
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Beklen, A., Tüter, G., Sorsa, T., Hanemaaijer, R., Virtanen, I., Tervahartiala, T., and Konttinen, Y. T.
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PERIODONTITIS ,GINGIVAL fluid ,COLLAGENASES ,METALLOPROTEINASES ,PERIODONTAL ligament ,IMMUNOHISTOCHEMISTRY - Abstract
Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil-derived proMMP-8 and -9. Immuno-histochemistry disclosed MMP-3 in gingival fibroblasts in periodontitis. Cultured gingival fibroblasts released only pro-MMP-3 when stimulated with tumor necrosis factor-α. However, Western blot revealed partially activated MMP-3, MMP-8, and MMP-9 in periodontitis GCF. Active MMP-8 (p < 0.05) and MMP-9 (p < 0.05) correlated with the presence of active MMP-3. It seems that resident gingival fibroblasts produce pro-MMP-3 in GCF, where it becomes activated, probably by cathepsin G or elastase released by neutrophils. Active MMP-3 then activates neutrophil-derived pro-MMP-8 and -9. Different tissue compartments/cells exert co-operative actions in mutual local MMP activation cascades. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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8. Painful Tooth Stimulation Elevates Matrix Metalloproteinase-8 Levels Locally in Human Gingival Crevicular Fluid.
- Author
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Avellan, N.-L., Sorsa, T., Tervahartiala, T., Mäntylä, P., Forster, C., and Kemppainen, P.
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METALLOPROTEINASES ,NEUROTRANSMITTERS ,NEUROPEPTIDES ,GINGIVAL fluid ,NERVE tissue proteins ,BIOLOGICAL transport ,DENTAL research ,DENTAL pulp diseases ,GINGIVA ,INFLAMMATION - Abstract
Recent studies have demonstrated that pulpal pain can induce neurogenic inflammatory reactions in gingiva and the expression of pro-inflammatory neuropeptides in gingival crevicular fluid (GCF). Neuropeptides co-ordinate the activity of immunoeffector cells and may influence the secretion of matrix metalloproteinase (MMP)-8, the major tissue-destructive protease in GCF. With this background, we studied whether experimental pulpal pain can trigger changes in GCF MMP-8 levels. The molecular forms of MMP-8 in the GCF of stimulated and non-stimulated teeth were analyzed by Western immunoblot, and MMP-8 levels by quantitative immunofluorometric assay. Painful stimulation of the upper incisor provoked significant elevations in GCF MMP-8 levels of the stimulated tooth. Western immunoblot revealed elevations in both neutrophil- and mesenchymaltype MMP-8 isoforms. At the same time, the GCF MMP-8 levels of the non-stimulated teeth were not changed. Analysis of these data indicated that pulpal pain can induce local elevations in MMP-8 levels in GCF. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
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9. The in vivo Levels of Matrix Metalloproteinase-1 and -8 in Gingival Crevicular Fluid during Initial Orthodontic Tooth Movement.
- Author
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Apajalahti, S., Sorsa, T., Railavo, S., and Ingman, T.
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ORTHODONTICS ,CORRECTIVE orthodontics ,DENTAL chemistry ,GINGIVAL fluid ,METALLOPROTEINASES ,COLLAGENASES - Abstract
Orthodontic force induces biochemical responses in the periodontal ligament (PDL), but the matrix metalloproteinase (MMP)-dependent molecular mechanisms in orthodontically induced periodontal remodeling have remained unclear. Previous studies indicate that mechanical stress induces MMP-1 production in human PDL cells in vitro. We tested the hypothesis whether the in vivo levels, molecular forms, and degree of activation of MMP-1 and MMP-8 in gingival crevicular fluid (GCF) reflect an early stage of orthodontic tooth movement. Molecular forms of MMP-1 and MMP-8 were analyzed by Western blot, and MMP-8 levels by quantitative immunofluorometric assay (IFMA). The results showed that GCF MMP-8 levels for orthodontically treated teeth were significantly higher at 4-8 hrs after force application than before activation, and when compared with the control teeth (p < 0.05). Analysis of our data indicates that the cells within the periodontium are up-regulated to produce MMP-8, and the increased expression and activation of GCF MMP-8 reflect enhanced periodontal remodeling induced by orthodontic force. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
10. MMP-9 Activation by Tumor Trypsin-2 Enhances in vivo Invasion of Human Tongue Carcinoma Cells.
- Author
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Nyberg, P., Moilanen, M., Paju, A., Sarin, A., Stenman, U.-H., Sorsa, T., and Salo, T.
- Subjects
METALLOPROTEINASES ,CANCER cells ,TONGUE cancer ,TRYPSIN ,CANCER invasiveness ,TUMORS ,CELL lines ,PAPILLOMAVIRUSES ,SQUAMOUS cell carcinoma - Abstract
Various human cancer cells express tumorassociated trypsinogen-2 (TAT-2), which can efficiently activate matrix metalloproteinases (MMPs) in vitro. MMP-2 and MMP-9 are particularly associated with the invasive malignant potential of several tumors. To investigate the role of TAT-2 in tumor invasion, we overexpressed TAT-2 in two malignant human squamous cell carcinoma cell lines of tongue and in non-malignant human papilloma virus transformed gingival keratinocytes. The TAT-2 overexpression significantly increased the levels of active MMP-9 in the most malignant cell line. TAT-2-transfected cells intravasated (invaded blood vessels) up to 60% more efficiently than did the control cells in an in vivo chick embryo chorioallantoic membrane invasion model. This increased intravasation was almost completely abolished by a specific tumor-associated trypsin inhibitor (TATI). These results indicate that TAT-2 has a role in the invasive growth of tumors, either alone or in cascade with gelatinases, especially by generating active MMP-9. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
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11. The Localization of Matrix Metalloproteinase-20 (MMP-20, Enamelysin) in Mature Human Teeth.
- Author
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Sulkala, M., Larmas, M., Sorsa, T., Salo, T., and Tjäderhane, L.
- Subjects
METALLOPROTEINASES ,DENTIN ,DENTAL pulp ,DENTAL enamel ,DENTAL caries ,IMMUNOHISTOCHEMISTRY ,DENTINOGENESIS - Abstract
MMP-20 (enamelysin), the matrix metalloproteinase family member discovered in the enamel organ, has also been detected in odontoblasts during dentin formation. We studied the presence and localization of MMP-20 in mature human teeth in health and disease. In immunohistochemistry, MMP-20-positive staining was observed most intensively in the radicular odontoblastic layer and also in dilated dentinal tubuli of caries lesions. By Western blotting, MMP-20 was detected in odontoblasts and pulp tissue of both sound and carious teeth, in dentinal fluid and dentin of sound teeth, but not in soft carious dentin. We conclude that MMP-20 produced during primary dentinogenesis is incorporated into dentin and may be released during caries progression. The main cellular source of MMP-20 in the dentin-pulp complex is the odontoblasts, which secrete MMP-20 into the dentinal fluid. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
12. Regulation and Interactions of MT1-MMP and MMP-20 in Human Odontoblasts and Pulp Tissue in vitro.
- Author
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Palosaari, H., Ding, Y., Larmas, M., Sorsa, T., Bartlett, J. D., Salo, T., and Tjäderhane, L.
- Subjects
DENTAL pulp ,DENTIN ,WESTERN immunoblotting ,REGULATION of cell growth ,MESSENGER RNA ,GROWTH factors ,METALLOENZYMES - Abstract
MT1-MMP is a cell-membrane-bound metalloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-β1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms. BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-β1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation of MMP-20 by MT1-MMP. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
13. Expression and Regulation of MMP-20 in Human Tongue Carcinoma Cells.
- Author
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Väänänen, A., Srinivas, R., Parikka, M., Palosaari, H., Bartlett, J. D., Iwata, K., Grenman, R., Stenman, U. -H., Sorsa, T., and Salo, T.
- Subjects
TONGUE cancer ,METALLOPROTEINASES ,TUMOR treatment ,EXTRACELLULAR matrix proteins ,COLLAGEN ,GROWTH factors ,DENTAL materials - Abstract
Human matrix metalloproteinase-20 (MMP-20, enamelysin) fragments the enamel-specific protein amelogenin and has been shown to be synthesized exclusively by odontoblasts and ameloblasts and in certain odontogenic tumors. Here we demonstrate, for the first time, the expression of MMP-20 mRNA and protein in two carcinoma cell lines originating from the tongue. Treatment of the SCC-25 and HSC-3 cells with phorbol 12-myristate 13-acetate (10 nmol/L) up-regulated MMP-20 mRNA and protein expression by up to 1.6-fold, but transforming growth factor beta (10 ng/mL) had no effect. The latent proform of recombinant (r) human MMP-20 was converted by tumor-related trypsin-2. Activated rMMP-20 did not degrade type I or type II collagen, but efficiently hydrolyzed fibronectin, type IV collagen, laminin-1 and -5, tenascin-C, and β-casein. This implies that MMP-20 not only participates in dental matrix remodeling but is also present in tongue carcinoma cells. [ABSTRACT FROM AUTHOR]
- Published
- 2001
14. Human Odontoblast Culture Method: The Expression of Collagen and Matrix Metalloproteinases (MMPs).
- Author
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Tjäderhane, L., Palosaari, H., Wahlgren, J., Larmas, M., Sorsa, T., and Salo, T.
- Subjects
DENTAL pulp ,DENTAL pulp cavities ,GROWTH factors ,EXTRACELLULAR matrix ,METALLOPROTEINASES ,MESSENGER RNA ,DENTIN - Abstract
Studies on mature human odontoblasts have suffered for the lack of in vitro models. We recently introduced a human odontoblast and pulp tissue organ culture method, in which the odontoblasts are cultured in the pulp chamber after removal of the pulp tissue, and the pulp tissue can be cultured separately (Tjäderhane et al., 1998a). With this method, we have studied the effects of growth factors on the expression of collagen and extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinases (MMPs), in mature human odontoblasts. TGF-β1 was selected because of its ability to regulate the response of the dentin-pulp complex to external irritation. The effect of TGF-β1 (10 ng/mL) on proα1(I) collagen mRNA was analyzed by quantitative PCR, and type I procollagen propeptide (PINP) was analyzed from conditioned culture media with RIA. Odontoblast media were also assayed for respective type III procollagen propeptide (PIIINP). TGF-β had a negligible effect on collagen mRNA expression or protein synthesis, indicating that TGF-β alone does not markedly induce dentin matrix formation per se in the human dentin-pulp complex (Palosaari et al., 2001). However, TGF-β1 seems to regulate MMP expression in mature human odontoblasts differentially. A strong downregulation of MMP-8 (Palosaari et al, 2000), a modest down-regulation of MMP-20 (Tjäderhane et al., 2000), and considerable up-regulation of MMP-9, with no apparent effect on MMP-2 expression (Tjäderhane et ah, 1998b), indicate that growth factors may affect the matrix synthesis by controlling the expression and activity of MMPs instead of collagen synthesis. The altered expression of MMPs may result in altered ECM formation, which in turn may contribute to the formation of atubular reparative dentin. [ABSTRACT FROM AUTHOR]
- Published
- 2001
15. The Effects of MMP Inhibitors on Human Salivary MMP Activity and Caries Progression in Rats.
- Author
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Sulkala, M., Wahlgren, J., Larmas, M., Sorsa, T., Teronen, O., Salo, T., and Tjäderhane, L.
- Subjects
METALLOPROTEINASES ,DENTAL caries research ,SALIVARY proteins ,EXTRACELLULAR matrix proteins ,EXTRACELLULAR enzymes ,DENTIN ,LABORATORY rats - Abstract
Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with
125 I-labeled gelatin as a substrate. To address the role of MMPs in the progression of fissure caries in vivo, we administered the MMP inhibitors CMT- 3 and zoledronate to young rats per os for 7 weeks, 5 days a week. Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars. Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3. CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats. These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression. [ABSTRACT FROM AUTHOR]- Published
- 2001
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16. Tumor Necrosis Factor-a and its Receptors, p55 and p75, in Gingiva of Adult Periodontitis.
- Author
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Tervahartiala, T., Koski, H., Xu, J.-W., Häyrinen-Immonen, R., Hietanen, J., Sorsa, T., and Konttinen, Y.T.
- Subjects
TUMOR necrosis factors ,PERIODONTITIS ,METALLOPROTEINASES ,OSTEOCLASTS ,IMMUNOHISTOCHEMISTRY ,CYTOKINES ,GINGIVA - Abstract
Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, can stimulate matrix metalloproteinase synthesis and osteoclastic bone resorption. We hypothesized that elevated expression of TNF-α and its p55 and p75 receptors (TNF-R) in gingival tissue might associate with periodontitis. Immunohistochemistry was used for the study of the localization of TNF-α and its p55 and p75 TNF-R in adult periodontitis (AP) gingival tissue, in comparison with that in healthy control specimens. TNF-α and p55 TNF-R were detected in sulcular epithelial basal cells and in monocyte/macrophages, fibroblasts, and endothelial cells in the AP gingival tissue specimens, but mainly in fibroblasts and endothelial cells in control specimens. P75 TNF-R was occasionally found in monocyte/macrophage-like cells in gingival tissue specimens. The percentage of TNF-α-containing cells was not increased in AP compared with controls (13.2% + 6.1% vs. 12.8% ± 7.6%), but, due to the increased cellularity of AP samples, the number of TNF-α positive cells/mm² was clearly increased (1621 ± 663 vs. 664 ± 191, p > 0.001). Thus, AP gingival tissue has an elevated expression of TNF-α and especially its p55 receptor, suggesting that TNF-α may contribute to tissue degradation in periodontitis. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
17. The in vivo Expression of the Collagenolytic Matrix Metalloproteinases (MMP-2, -8, -13, and -14) and Matrilysin (MMP-7) in Adult and Localized Juvenile Periodontitis.
- Author
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Tervahartiala, T., Pirilä, E., Ceponis, A., Maisi, P., Salo, T., Tuter, G., Kallio, P., Törnwall, J., Srinivas, R., Konttinen, Y. T., and Sorsa, T.
- Subjects
PERIODONTITIS ,METALLOPROTEINASES ,EPITHELIUM ,PERIODONTAL ligament ,TOOTH loss ,KERATINOCYTES - Abstract
Periodontal inflammation is characterized by irreversible degradation of periodontal ligament collagen fibers leading to loss of tooth attachment. Cultured gingival keratinocytes and fibroblasts express, in vitro, various matrix metalloproteinases (MMPs) which can degrade fibrillar collagens. We hypothesized that several MMPs are also synthesized in vivo by sulcular epithelium, and analyzed the collagenolytic MMPs (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in gingival tissue specimens and gingival crevicular fluid from adult and localized juvenile periodontitis patients by in situ hybridization, immunohistochemistry, and Western immunoblotting. MMP-2, -7, -8, and -13 were expressed in gingival sulcular epithelium. MMP-7 and -13 were also located in fibroblasts and macrophages, and MMP-8 in neutrophils. MMP-8- and -13- positive cells/mm² were higher in periodontitis gingiva when compared with healthy control tissue (p < 0.01). In periodontal diseases, gingival sulcular epithelium expresses several, rather than a single, collagenolytic MMPs, and this proteolytic cascade is evidently responsible for the tissue destruction characteristic of adult and juvenile periodontitis. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
18. Collagenases in Different Categories of Peri-implant Vertical Bone Loss.
- Author
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Ma, J., Kitti, U., Teronen, O., Sorsa, T., Husa, V., Laine, P., Rönkä, H., Salo, T., Lindqvist, C., and Konttinen, Y. T.
- Subjects
COLLAGENASES ,DENTAL implants ,BONE resorption ,INFLAMMATION ,BONE growth ,GINGIVA - Abstract
The loosening of dental implants is associated with peri-implant vertical bone loss. The mechanisms and mediators of this bone destruction are not known. To test the hypothesis that collagenase-2 and collagenase-3 might be markers or maybe even mediators in this process, we measured collagenase-2 (time-resolved immunofluorometric assay) and collagenase-3 (quantitative immunoblot) in peri-implant sulcus fluid in 49 implant sites in 13 patients. Vertical bone loss was graded as being < 1 mm, from 1 to 3 mm, or > 3 mm. The severity of inflammation, as rated according to Gingival Index, did not correlate with the category of bone loss (p > 0.05). Collagenase-2 and collagenase-3 were higher (p < 0.05) in the group which had lost > 3 mm of bone than in the two other groups. Gingival Index is not a clinically important marker for bone loss, but collagenase-2 and collagenase-3 in peri-implant sulcus fluid are. They might participate in peri-implant osteolysis. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
19. The Expression of MMP-8 in Human Odontoblasts and Dental Pulp Cells is Down-regulated by TGF-β1.
- Author
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Palosaari, H., Wahlgren, J., Larmas, M., Rönkä, H., Sorsa, T., Salo, T., and Tjäderhane, L.
- Subjects
COLLAGENASES ,DENTAL pulp ,DENTIN ,METALLOPROTEINASES ,NEUTROPHILS - Abstract
Recent findings show that matrix metalloproteinase-8 (MMP-8) is expressed, in addition to neutrophils, by human chondrocytes, cultured fibroblasts, and endothelial cells. We investigated the expression of MMP-8 in other human mesenchyme-derived cells, odontoblasts, and pulp tissue. Odontoblasts and pulp tissue were collected from extracted human teeth for MMP-8 mRNA analysis with reverse-transcription/polymerase chain-reaction (RT-PCR) and Southern blot. The expression, localization, and secretion of MMP-8 protein were studied with Western blot, immunohistochemistry, and immunofluorometric assay. The effect of TGF-β1 (10 ng/mL) on the expression, secretion, and concentration of secreted MMP-8 was studied by odontoblast and pulp tissue culture methods (Tjäderhane et al., 1998a). RT-PCR demonstrated MMP-8 mRNA expression in native and cultured odontoblasts and pulp tissue and cultured pulp fibroblasts, with a 522-bp transcript comparable with that of bone marrow cells. The specificity of PCR was confirmed with Southern blot. Western blot with MMP-8-specific antibody detected 65- and 50-kDa proteins in native samples, representing latent and active forms of mesenchymal-type MMP-8, and in the conditioned odontoblast culture media, 50-kDa protein was observed. TGF-β down-regulated the MMP-8 mRNA and concentration of secreted protein in both cultures. Immunohistochemical staining detected MMP-8 in odontoblasts. These findings indicate that mesenchyme-derived cells of the dentin-pulp complex express, synthesize, and activate MMP-8, which may, in concert with odontoblast-derived gelatinases, participate in organization of dentin organic matrix prior to mineralization. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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- View/download PDF
20. THE EFFECTS OF CHEMICALLY MODIFIED TETRACYCLINES (CMTS) ON HUMAN KERATINOCYTE PROLIFERATION AND MIGRATION.
- Author
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MAKELA, M., SORSA, T., UITTO, V.-J., SALO, T., TERONEN, O., and LARJAVA, H.
- Subjects
TETRACYCLINES ,KERATINOCYTES ,CELL proliferation ,CELL migration ,PERIODONTITIS ,METALLOPROTEINASES - Abstract
Chemically modified non-antimicrobial tetracycline derivatives and other low-molecular-weight synthetic matrix metalloproteinase (MMP) inhibitors inhibited keratinocyte migration. Since 72-kDa gelatinase-A (MMP-2) was the major gelatinase in our culture conditions, the results suggest that this MMP may be important in the regulation of keratinocyte mobility. On the other hand, we measured only gelatinase activities (MMP-2 and -9) present in culture medium, and therefore the results do not reveal how the inhibitors affect other MMPs as well as MMP levels close to the cell membranes. Overall, CMTs were found to be efficient in the inhibition of keratinocyte migration. [ABSTRACT FROM AUTHOR]
- Published
- 1998
21. TETRACYCLINES INHIBIT CONNECTIVE TISSUE BREAKDOWN BY MULTIPLE NON ANTIMICROBIAL MECHANISMS.
- Author
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GOLUB, L. M., LEE, H.-M., RYAN, M. E., GIANNOBILE, W. V., PAYNE, J., and SORSA, T.
- Subjects
TETRACYCLINES ,CONNECTIVE tissues ,METALLOPROTEINASES ,COLLAGENASES ,GERMFREE animals ,LABORATORY rats - Abstract
A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected nonantimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a variety of dental {e.g., adult periodontitis) and medical {e.g., arthritis, osteoporosis, cancer) diseases. The site on the TC molecule responsible for its MMP-inhibitory activity was identified which led to the development of a series of chemically modified non-antimicrobial analogs, called CMTs, which also have therapeutic potential but do not appear to induce antibiotic side-effects. Longitudinal double-blind studies on humans with adult periodontitis have demonstrated that a sub-antimicrobial dose of doxycycline (previously reported to suppress collagenase activity in the periodontal pocket) is safe and effective and has recently been approved by the FDA as an adjunct to scaling and root planing. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
22. INHIBITION OF MMP SYNTHESIS BY DOXYCYCLINE AND CHEMICALLY MODIFIED TETRACYCLINES (CMTs) IN HUMAN ENDOTHELIAL CELLS.
- Author
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HANEMAAIJER, R., VlSSER, H., KOOLWIJK, P., SORSA, T., SALO, T., GOLUB, L. M., and VAN HlNSBERGH, V. W. M.
- Subjects
TETRACYCLINES ,ENDOTHELIUM ,COLLAGENASES ,ENZYME inhibitors ,METALLOPROTEINASES ,ANTIBIOTICS - Abstract
Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 LAM) completely inhibited the phorbol-12-myristate-13-acetate (PMA)-mediated induction of MMP-8 and MMP-9, as measured by Western blotting and gelatin zymography, respectively. The inhibition was also observed at the mRNA level. No effect was observed on the expression of MMP-2 and of the MMP inhibitors TIMP-1 and TIMP-2. Chemically modified tetracyclines (CMTs) showed an inhibition similar to that of doxycycline, albeit less efficient. These observations demonstrate that endothelial cells display a specific regulation of MMPs, which may have implications for the pharmaceutical interaction in angiogenesis and angiogenesis-related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
23. The Activation and Function of Host Matrix Metalloproteinases in Dentin Matrix Breakdown in Caries Lesions.
- Author
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Tjäderhane, L., Larjava, H., Sorsa, T., Uitto, V.-J., Larmas, M., and Salo, T.
- Subjects
SALIVA analysis ,METALLOPROTEINASES ,DENTAL caries research ,EXTRACELLULAR enzymes ,DENTIN ,COLLAGEN - Abstract
Matrix metalloproteinases (MMPs) are a family of enzymes which, in concert, are capable of degrading collagen. We investigated whether human MMPs could participate in the degradation of dentin organic matrix after demineralization. We performed Western blot analyses using MMP-specific antibodies to identify MMPs in human dental caries lesions. Enzymography and functional activity assays, with
125 I-labeled gelatin as substrate or quantitating the degradation of type I collagen, were used to determine the activity of purified and salivary gelatinolytic (MMP-2 and MMP-9) and collagenolytic (MMP-8) enzymes with and without acid-activation in pHs relevant to caries. Respective analyses were done with caries-related bacteria. We performed electron microscope analyses to assess the degradative activity of sterilized salivary host MMPs on demineralized human dentin. Human MMP-2, MMP-8, and MMP-9 were identified in demineralized dentinal lesions. The latent purified forms of these enzymes were activated at low pH (4.5), followed by neutralization, mimicking the conditions during caries progression. Incubation of human saliva at low pH followed by neutralization resulted in a four-fold increase in the gelatinolytic activity. No gelatinolytic or collagenolytic activity was observed in bacterial samples. The activated enzymes in saliva degraded demineralized dentin organic matrix in vitro. These results demonstrate the pH-dependent activation mechanism of MMPs, which may have a distinct role in different physiological and pathological conditions. They further demonstrate that host MMPs, activated by bacterial acids, have a crucial role in the destruction of dentin by caries. [ABSTRACT FROM AUTHOR]- Published
- 1998
24. Human Neutrophil Collagenase MMP-8 in Peri-implant Sulcus Fluid and its Inhibition by Clodronate.
- Author
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Teronen, O., Konttinen, Y. T., Lindqvist, C., Salo, T., Ingman, T., Lauhio, A., Ding, Y., Santavirta, S., and Sorsa, T.
- Subjects
COLLAGENASES ,DENTAL implants ,PERIODONTAL disease ,PERIODONTICS ,GINGIVAL diseases ,PERIODONTITIS ,TOOTH mobility ,PROTEOLYTIC enzymes ,DENTAL research - Abstract
The exact molecular mechanisms of the loosening of a dental implant are not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix metalloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently used in bone-resorption-related diseases in humans. The mechanisms of bisphosphonate action are not clarified. Collagenase activity in diseased PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immunoreactives MMP-8 compared with the healthy PISF. The residual latent collagenase activity in the diseased PISF was activated by gold thioglucose and inhibited completely by 100 µM of doxycycline closely resembling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in diseased but not in clinically healthy PISF may prove to be a useful biochemical indicator to monitor peri-implant health and disease. Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC
50 ] was achieved by 150 µM of clodronate), an osteoactive, anti-resorptive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the loosening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dental ligament destruction. Potential new therapeutic indications based on the collagenase-inhibiting effect of clodronate provide potential new therapeutic indications for a variety of diseases involving connective tissue breakdown, such as periodontal disease, arthritides, and tumor invasion. [ABSTRACT FROM AUTHOR]- Published
- 1997
- Full Text
- View/download PDF
25. Membrane Components of Treponema denticola Trigger Proteinase Release from Human Polymorphonuclear Leukocytes.
- Author
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Ding, Y., Uitto, V.-J., Haapasalo, M., Lounatmaa, K., Konttinen, Y. T., Salo, T., Grenier, D., and Sorsa, T.
- Subjects
PERIODONTITIS ,TREPONEMA ,PROTEINASES ,NEUTROPHILS ,METALLOPROTEINASES ,ORAL microbiology ,TRANSMISSION electron microscopy - Abstract
Abstract. Tissue destruction during periodontitis is believed to be primarily brought about by leukocyte proteinases. We postulate that oral spirochetes cause discharge of polymorphonuclear leukocyte (PMN) lysosomal enzymes. Effects of Treponema denticola 53-kDa outer membrane protein, lipopolysaccharide (LPS), and peptidoglycan on degranulation of matrix metalloproteinases (MMP)-8 (collagenase) and -9 (gelatinase), cathepsin G, and elastase by human peripheral blood PMNs were studied by specific enzyme assays and Western blot analysis. T. denticola 53- kDa outer membrane protein was found to be a particularly efficient inducer of MMP-8 release. The induction was comparable with that of phorbol myristate acetate, a known inducer of PMN specific granule discharge. All of the treponemal substances, most notably the 53-kDa protein and LPS, induced release of MMP-9, a component of C-type granules. Both collagenase and gelatinase released from PMNs were mostly in active forms. Release of cathepsin G and elastase was also observed with the 53-kDa protein treatment. The other T. denticola substances did not induce release of these serine proteinases. Lactate dehydrogenase was not released from PMNs by the treatments, indicating that the degranulation was specific and not caused by toxic effects of the substances. This was confirmed by transmission electron microscopy of PMNs treated with the 53-kDa protein that showed rapid vacuole formation and cell shape changes but no disintegration of the cells. Thus, T. denticola may participate in the PMN-dependent extracellular matrix degradation during the course of periodontal inflammation by triggering the secretion and activation of matrix metalloproteinases. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
26. Human Neutrophil Gelatinase and Associated Lipocalin in Adult and Localized Juvenile Periodontitis.
- Author
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Westerlund, U., Ingman, T., Lukinmaa, P.-L., Salo, T., Kjeldsen, L., Borregaard, N., Tjäderhane, L., Konttinen, Y.T., and Sorsa, T.
- Subjects
METALLOPROTEINASES ,GINGIVITIS ,GINGIVAL fluid ,LEUCOCYTES ,SALIVA ,IMMUNOHISTOCHEMISTRY ,PERIODONTITIS ,NEUTROPHILS - Abstract
The article presents research into the presence and localization of matrix metalloproteinases-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in adult periodonitits (AP) and localized juvenile periodontitis (LJP) gingival tissue specimens by immunohistochemistry. The activities of gelatinases by Western blot, enzymography, and measurements using radioactive gelatin were substrate in gingival crevicular fluid (GCF) and saliva. It was concluded that extravasated degranulating polymorphonuclear leukocytes (PMNs) are a major source of MMP-9 and NGAL in periodontitis gingiva, GCF, and saliva.
- Published
- 1996
- Full Text
- View/download PDF
27. Letter to the Editor: "MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery".
- Author
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Nwhator, S.O., Umeizudike, K.A., and Sorsa, T.
- Subjects
POLYETHYLENE glycol ,HYDROGELS ,BIOLOGICAL tags ,BIOMEDICAL materials ,DRUG delivery systems ,PHARMACEUTICAL gels ,PROTEOLYTIC enzymes - Published
- 2019
- Full Text
- View/download PDF
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