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Inicio Revista Clínica de Periodoncia, Implantología y Rehabilitación Oral Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y...
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Vol. 4. Núm. 1.
Páginas 17-21 (Abril 2011)
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Vol. 4. Núm. 1.
Páginas 17-21 (Abril 2011)
Open Access
Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomática
Immunodetection of matrix metalloproteinases (MMPs)-2, -9, -13 and -14 in periapical lesions associated with asymptomatic apical periodontitis
Visitas
1843
V. Mundi Burgos1,5, A. Dezerega Piwonka2,5, C. Osorio Alfaro1,5, N. Dutzan Muñoz3,5, M.E. Franco Martínez4, A.V. Ortega Pinto4, M. Hernández Ríos4,5,
Autor para correspondencia
mhernandezrios@gmail.com

Correspondencia autor: Laboratorio de Biología Periodontal, Departamento de Odontología Conservadora, Facultad de Odontología, Universidad de Chile. Chile.
1 Programa de Magíster en Ciencias Odontológicas. Facultad de Odontología, Universidad de Chile. Chile
2 Área de Endodoncia, Departamento de Odontología Conservadora. Facultad de Odontología, Universidad de Chile. Chile
3 Área de Periodoncia, Departamento de Odontología Conservadora. Facultad de Odontología, Universidad de Chile. Chile
4 Área de Patología, Departamento de Patología. Facultad de Odontología, Universidad de Chile. Chile
5 Laboratorio de Biología Periodontal. Facultad de Odontología, Universidad de Chile. Chile
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Información del artículo
Resumen

La periodontitis apical asintomática (PAa) es una patología infecciosa caracterizada por destrucción ósea perirradicular asociada a un proceso inflamatorio crónico y producción de mediadores inflamatorios, entre los cuales se encuentran las metaloproteinasas de matriz extracelular (MMPs). Entre éstas, las MMPs-13, -14, -2 y -9, son producidas por el tejido óseo y degradan sinérgicamente el colágeno tipo I, principal componente de los tejidos periodontales, y gelatina, producto de la degradación y desnaturación del colágeno. El objetivo de este estudio fue determinar el patrón de expresión de las MMPs-2, -9, -13 y -14 en granulomas periapicales (GPAs), quistes radiculares inflamatorios (QRIs) y ligamento periodontal sano (LS).

Materiales y Métodos

Se seleccionaron 12 pacientes con diagnóstico clínico de PAa e indicación de exodoncia a partir de los cuales se obtuvieron biopsias de lesiones periapicales (LPAs). Como controles, se seleccionaron 7 individuos con indicación de exodoncia de premolares por ortodoncia, obteniéndose biopsias de LS. Se efectuó el diagnóstico anátomo-patológico de los especímenes y se caracterizó la expresión de las MMPs en estudio mediante inmunohistoquímica.

Resultados

Las MMPs en estudio sólo se detectaron en GPAs y QRIs, y se inmunolocalizaron principalmente en el infiltrado inflamatorio de éstos. Adicionalmente, la MMP-2 se identificó en fibroblastos del tejido conectivo.

Conclusiones

MMPs-2, -9, -13 y -14 se expresan predominantemente en el infiltrado inflamatorio de las LPAs y no en LS, y por tanto se sugiere la participación de estos mediadores en la patogénesis de la PAa.

Palabras clave:
Periodontitis apical asintomática
lesiones periapicales
metaloproteinasas de matriz extracelular
Abstract

Asymptomatic apical periodontitis (aAP) is an infectious disease characterized by perirradicular bone destruction associated with chronic inflammation and release of inflammatory mediators, such as matrix metalloproteinases (MMPs). MMPs-13, -14 and -2, -9 are bone-expressed enzymes that can synergistically degrade collagen I, the main component of periodontal extracellular matrix, and gelatin, the product of degradation and denaturation of collagen. The aim of this study was to characterize the expression pattern of MMPs-2, -9, -13, and -14 in periapical granulomas (PGs), radicular cysts (RCs) and healthy periodontal ligament (PDL).

Materials and Methods

Individuals with clinical diagnosis of aAP and indication of extraction were selected (N=12), and biopsies of periapical lesions (PLs) were obtained. For controls, 7 subjects with indication of premolar extraction for orthodontic reasons were selected, and PDL biopsies were obtained. Samples were diagnosed by anatomopathological examination and immunohistochemical staining was carried out to characterize MMPs expression.

Results

MMPs-2, -9, -13 and -14 detection was limited to PLs and were localized mainly to inflammatory infiltrate on both, PGs and RCs. Additionally, MMP-2 was immunolocalized to fibroblasts from the connective tissue.

Conclusions

Whereas MMPs-2, -9, -13 and -14 were not detected in healthy periodontal ligament, they were highly expressed on inflammatory infiltrate from PGs and RCs, suggesting a role of these mediators in aAP pathogenesis.

Key words:
Asymptomatic apical periodontitis
periapical lesions
extracellular matrix metalloproteinases
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Referencias Bibliográficas
[1.]
G.N. Glickman.
AAE Consensus Conference on Diagnostic Terminology: background and perspectives.
J Endod, 35 (2009), pp. 1619-1620
[2.]
K. Takahashi.
Microbiological, pathological, inflammatory, immunological and molecular biological aspects of periradicular disease.
Int Endod J, 31 (1998), pp. 311-325
[3.]
A. Ortega, V. Fariña, A. Gallardo, I. Espinoza, S. Acosta.
Nonendodontic periapical lesions: A retrospective study in Chile.
Int Endod J, 40 (2007), pp. 386-390
[4.]
S. Liapatas, M. Nakou, D. Rontogianni.
Inflammatory infiltrate of chronic periradicular lesions: An immunohistochemical study.
Int Endod J, 36 (2003), pp. 464-471
[5.]
P.N. Ramachandran Nair, G. Pajarola, H.E. Schroeder.
Types and incidence of human periapical lesions obtained with extracted teeth.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 81 (1996), pp. 93-102
[6.]
T. Matsuo, S. Ebisu, Y. Shimabukuro, T. Ohtake, H. Okada.
Quantitative analysis of immunocompetent cells in human periapical lesions: correlations with clinical findings of the involved teeth.
[7.]
P.N. Nair.
Pathogenesis of apical periodontitis and the causes of endodontic failures.
Crit Rev Oral Biol Med, 15 (2004), pp. 348-381
[8.]
W.C. Parks, C.L. Wilson, Y.S. Lopez-Boado.
Matrix metalloproteinases as modulators of inflammation and innate immunity.
Nat Rev Immunol, 4 (2004), pp. 617-629
[9.]
R. Visse, H. Nagase.
Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry.
[10.]
M.J. Belmar, C. Pabst, B. Martínez, M. Hernández.
Gelatinolytic activity in gingival crevicular fluid from teeth with periapical lesions.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 105 (2008), pp. 801-806
[11.]
M. Hernández, J. Gamonal, T. Tervahartiala, P. Mantyla, O. Rivera, A. Dezerega, et al.
Associations between matrix metalloproteinase-8 and -14 and myeloperoxidase in gingival crevicular fluid from subjects with progressive chronic periodontitis: A longitudinal study.
J Periodontol, 81 (2010), pp. 1644-1652
[12.]
M. Hernández Ríos, T. Sorsa, F. Obregon, T. Tervahartiala, M.A. Valenzuela, P. Pozo, et al.
Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: Initial evidence for MMP-13/MMP-9 activation cascade.
J Clin Periodontol, 36 (2009), pp. 1011-1017
[13.]
J. Wahlgren, P. Maisi, T. Sorsa, M. Sutinen, T. Tervahartiala, E. Pirila, et al.
Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions.
J Pathol, 194 (2001), pp. 217-224
[14.]
S.J. Shin, J.I. Lee, S.H. Baek, S.S. Lim.
Tissue levels of matrix metalloproteinases in pulps and periapical lesions.
[15.]
R. Leonardi, E. Lanteri, F. Stivala, S. Travali.
Immunolocalization of CD44 adhesion molecules in human periradicular lesions.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 89 (2000), pp. 480-485
[16.]
E. Carneiro, R. Menezes, G.P. Garlet, R.B. Garcia, C.M. Bramante, R. Figueira, et al.
Expression analysis of matrix metalloproteinase-9 in epithelialized and nonepithelialized apical periodontitis lesions.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 107 (2009), pp. 127-132
[17.]
H.D. Buzoglu, H. Unal, C. Ulger, S. Mert, S. Kucukyildirim, N. Er.
The zymographic evaluation of gelatinase (MMP-2 and -9) levels in acute and chronic periapical abscesses.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 108 (2009), pp. 121-126
[18.]
F.W. Paula-Silva, L.A. da Silva, Y.L. Kapila.
Matrix metalloproteinase expression in teeth with apical periodontitis is differentially modulated by the modality of root canal treatment.
J Endod, 36 (2010), pp. 231-237
[19.]
P.A. Hill, G. Murphy, A.J. Docherty, R.M. Hembry, T.A. Millican, J.J. Reynolds, et al.
The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts.
J Cell Sci, 107 (1994), pp. 3055-3064
[20.]
P.A. Hill, A.J. Docherty, K.M. Bottomley, J.P. O’Connell, J.R. Morphy, J.J. Reynolds, et al.
Inhibition of bone resorption in vitro by selective inhibitors of gelatinase and collagenase.
Biochem J, 308 (1995), pp. 167-175
[21.]
L.M. Golub, H.M. Lee, M.E. Ryan, W.V. Giannobile, J. Payne, T. Sorsa.
Tetracyclines inhibit connective tissue breakdown by multiple nonantimicrobial mechanisms.
Adv Dent Res, 12 (1998), pp. 12-26
[22.]
M.V. Corotti, W.F. Zambuzzi, K.B. Paiva, R. Menezes, L.C. Pinto, V.S. Lara, et al.
Immunolocalization of matrix metalloproteinases -2 and -9 during apical periodontitis development.
Arch Oral Biol, 54 (2009), pp. 764-771
[23.]
N. Kawashima, N. Suzuki, G. Yang, C. Ohi, S. Okuhara, H. Nakano- Kawanishi, et al.
Kinetics of RANKL.
RANK and OPG expressions in experimentally induced rat periapical lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 103 (2007), pp. 707-711
[24.]
F.W. de Paula-Silva, N.J. D'Silva, L.A. da Silva, Y.L. Kapila.
High matrix metalloproteinase activity is a hallmark of periapical granulomas.
J Endod, 35 (2009), pp. 1234-1242
[25.]
M. Hernández, B. Martínez, J.M. Tejerina, M.A. Valenzuela, J. Gamonal.
MMP-13 and TIMP-1 determinations in progressive chronic periodontitis.
J Clin Periodontol, 34 (2007), pp. 729-735
[26.]
T. Ingman, T. Tervahartiala, Y. Ding, H. Tschesche, A. Haerian, D.F. Kinane, et al.
Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients.
J Clin Periodontol, 23 (1996), pp. 1127-1132
[27.]
X.S. Puente, L.M. Sanchez, C.M. Overall, C. Lopez-Otin.
Human and mouse proteases: A comparative genomic approach.
Nat Rev Genet, 4 (2003), pp. 544-558
[28.]
V.J. Uitto, K. Airola, M. Vaalamo, N. Johansson, E.E. Putnins, J.D. Firth, et al.
Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation.
Am J Pathol, 152 (1998), pp. 1489-1499
[29.]
S.L. Teitelbaum.
Bone resorption by osteoclasts.
Science, 289 (2000), pp. 1504-1508
[30.]
S.L. Teitelbaum.
Osteoclasts: What do they do and how do they do it?.
Am J Pathol, 170 (2007), pp. 427-435
[31.]
T. Ilgenli, S. Vardar-Sengul, A. Gurkan, T. Sorsa, S. Stackelberg, T. Kose, et al.
Gingival crevicular fluid matrix metalloproteinase-13 levels and molecular forms in various types of periodontal diseases.
[32.]
J.M. Freije, I. Diez-Itza, M. Balbin, L.M. Sanchez, R. Blasco, J. Tolivia, et al.
Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas.
J Biol Chem, 269 (1994), pp. 16766-16773
[33.]
R. Ala-aho, M. Ahonen, S.J. George, J. Heikkila, R. Grenman, M. Kallajoki, et al.
Targeted inhibition of human collagenase-3 (MMP-13) expression inhibits squamous cell carcinoma growth in vivo.
Oncogene, 23 (2004), pp. 5111-5123
[34.]
J. Wahlgren, A. Vaananen, O. Teronen, T. Sorsa, E. Pirila, J. Hietanen, et al.
Laminin-5 gamma 2 chain is colocalized with gelatinase-A (MMP-2) and collagenase-3 (MMP-13) in odontogenic keratocysts.
J Oral Pathol Med, 32 (2003), pp. 100-107
[35.]
J. Martel-Pelletier, J.P. Pelletier.
Wanted the collagenase responsible for the destruction of the collagen network in human cartilage!.
Br J Rheumatol, 35 (1996), pp. 818-820
[36.]
M. Hernández, M.A. Valenzuela, C. López-Otin, J. Álvarez, J.M. López, R. Vernal, et al.
Matrix metalloproteinase -13 is highly expressed in destructive periodontal disease activity.
J Periodontol, 77 (2006), pp. 1863-1870
[37.]
J.P. Mansell, J.F. Tarlton, A.J. Bailey.
Expression of gelatinases within the trabecular bone compartment of ovariectomized and parathyroidectomized adult female rats.
Bone, 20 (1997), pp. 533-538
[38.]
R.A. Greenwald, L.M. Golub, N.S. Ramamurthy, M. Chowdhury, S.A. Moak, T. Sorsa.
In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: Relationship to bone and cartilage degradation.
Bone, 22 (1998), pp. 33-38
[39.]
A.R. Folgueras, A.M. Pendas, L.M. Sanchez, C. Lopez-Otin.
Matrix metalloproteinases in cancer: From new functions to improved inhibition strategies.
Int J Dev Biol, 48 (2004), pp. 411-424
[40.]
Z. Metzger.
Macrophages in periapical lesions.
Endod Dent Traumatol, 16 (2000), pp. 1-8
[41.]
I.J. Marton, C. Kiss.
Protective and destructive immune reactions in apical periodontitis.
Oral Microbiol Immunol, 15 (2000), pp. 139-150
[42.]
R. Vernal, A. Dezerega, N. Dutzan, A. Chaparro, R. Leon, S. Chandia, et al.
RANKL in human periapical granuloma: possible involvement in periapical bone destruction.
[43.]
T.A. Silva, G.P. Garlet, V.S. Lara, W. Martins Jr., J.S. Silva, F.Q. Cunha.
Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases.
Oral Microbiol Immunol, 20 (2005), pp. 310-316
[44.]
V. Knauper, S. Cowell, B. Smith, C. López-Otin, M. O'Shea, H. Morris, et al.
The role of the C-terminal domain of human collagenase-3 (MMP- 13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction.
J Biol Chem, 272 (1997), pp. 7608-7616
[45.]
V. Knauper, H. Will, C. López-Otin, B. Smith, S.J. Atkinson, H. Stanton, et al.
Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme.
J Biol Chem, 271 (1996), pp. 17124-17131
[46.]
C.M. Overall.
Molecular determinants of metalloproteinase substrate specificity: Matrix metalloproteinase substrate binding domains, modules, and exosites.
Mol Biotechnol, 22 (2002), pp. 51-86
[47.]
L. Tjaderhane, T. Hotakainen, S. Kinnunen, M. Ahonen, T. Salo.
The effect of chemical inhibition of matrix metalloproteinases on the size of experimentally induced apical periodontitis.
Int Endod J, 40 (2007), pp. 282-289
[48.]
C.A. Owen, Z. Hu, C. Lopez-Otin, S.D. Shapiro.
Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase.
J Immunol, 172 (2004), pp. 7791-7803
[49.]
H. Kuula, T. Salo, E. Pirila, A.M. Tuomainen, M. Jauhiainen, V.J. Uitto, et al.
Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis.
Infect Immun, 77 (2009), pp. 850-859
[50.]
M. Hernández, J. Gamonal, T. Salo, T. Tervahartiala, M. Hukkanen, L. Tjaderhane, et al.
Reduced expression of lipopolysaccharide-induced CXC chemokine in Porphyromonas gingivalis-induced experimental periodontitis in matrix metalloproteinase-8 null mice.
J Periodontal Res, 46 (2011), pp. 58-66
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