Español    I    English              
Return to Index

Rev Clin Periodoncia Implantol Rehabil Oral. 2009;2:46-49
TRABAJO DE INVESTIGACIÓN [PDF]

Expresión de Formas Solubles de MMP-14 y CXCL12 en Periodontitis Crónica Progresiva

Soluble Forms of MMP-14 and CXCL12 Expression in Progressive ChronicPeriodontitis

Hernández M1,3, Tervahartiala T2, Rivera O3, Dezerega A3, Dutzan N3, Henríquez L3, Sorsa T2

1Profesor Asistente, Departamento de Patología, Facultad de Odontología, Universidad de Chile. Chile
2Departamento de Enfermedades Orales y Maxilofaciales, Hospital Central Helsinki, Instituto de Odontología, Universidad de Helsinki, Helsinki, Finlandia
3Laboratorio de Biología Periodontal, Facultad de Odontología, Universidad de Chile. Chile

Resumen

La perdida de tejidos de soporte durante la periodontitis crónica se asocia con la infiltración de leucocitos inflamatorios y la expresión desregulada de MMPs. CXCL12 es una potente quimioquina, mientras que MMP-14 presenta actividad colagenolitica y además es capaz de activar a otras colagenasas, como las MMPs -8 y -13. En este estudio analizamos la expresión de MMP-14 y CXCL12 en FCG de sujetos con periodontitis crónica progresiva.

Materiales y métodos
Se seleccionaron sujetos con periodontitis crónica progresiva y se tomaron muestras de FCG de sitios activos e inactivos (N=34). Mediante immunowestern blot se caracterizaron las formas solubles de la MMP-14 y CXCL12. La MMP-14 se cuantificó mediante densitometria, mientras que los niveles de CXCL12 se determinaron mediante ELISA.

Resultados
CXCL12 y MMP-14 se identificaron en todos los sujetos con progresión. En sitios activos la MMP-14 soluble demostró una tendencia a aumentar y se encontró una fuerte correlación positiva entre MMP-14 y CXCL12, mientras que en sitios inactivos no se encontró correlación alguna.

Conclusión
MMP-14 aumenta conjuntamente con CXCL12 a nivel de sitios activos y esta asociación podría estar relacionada con la perdida activa de soporte periodontal.

Palabras clave: MMP-14, CXCL12, periodontitis crónica progresiva.

Abstract

Support tissue loss during chronic periodontitis is associated with inflammatory leukocyte infiltrates and upregulation of MMP expression. CXCL12 is a potent leukocyte chemoattractant and MMP-14 is a collagenase capable to activate other collagenases such as MMPs -8 and -13. In this study we analyzed the expression of MMP-14 and CXCL12 in GCF of subjects with progressive chronic periodontitis.

Materials and methods
Chronic periodontitis subjects undergoing disease progression were selected. GCF samples were collected from active and inactive sites (N=34). Soluble MMP-14 and CXCL12 forms were characterized by immunowestern blot. MMP-14 was quantified by densitometric analysis and CXCL12 levels were determined by ELISA.

Results
In active sites, soluble MMP-14 showed a tendency to increase and a strong positive correlation was found between MMP-14 and CXCL12, whereas in inactive sites, no correlation was found.

Conclusions
MMP-14 increases together with CXCL12 in active sites and thus, interactions between these mediators could be associated with active loss of tooth support tissues.

Key words: MMP-14, CXCL12, progressive chronic periodontitis.

El Texto completo solo está disponible en PDF

 


Referencias bibliográficas

1.
M. Dahan,B. Nawrocki,R. Elkaim
Expression of matrix metalloproteinases in healthy and diseased human gingiva
J Clin Periodontol, 28 (2001), pp. 128-136
2.
J.M. Goodson,A.D. Haffajee,S.S. Socransky
The relationship between attachment level loss and alveolar bone loss
J Clin Periodontol, 11 (1984), pp. 348-359
3.
S. Jepsen,I.N. Springer,A. Buschmann,J. Hedderich,Y. Acil
Elevated levels of collagen crosslink residues in gingival tissues and crevicular fluid of teeth with periodontal disease
Eur J Oral Sci, 111 (2003), pp. 198-202
4.
R.A. Ashley
Clinical trials of a matrix metalloproteinase inhibitor in human periodontal disease. SDD Clinical Research Team
Ann N Y Acad Sci, 30 (1999), pp. 335-346
5.
M. Kiili,S.W. Cox,H.Y. Chen
Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue
J Clin Periodontol, 29 (2002), pp. 224-232
6.
T. Tervahartiala,E. Pirila,A. Ceponis
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
J Dent Res, 79 (2000), pp. 1969-1977
7.
T. Ohshiba,C. Miyaura,M. Inada,A. Ito
Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis
Br J Cancer, 88 (2003), pp. 1318-1326 http://dx.doi.org/10.1038/sj.bjc.6600858
8.
C.M. Overall
Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites
Mol Biotechnol, 22 (2002), pp. 51-86 http://dx.doi.org/10.1385/MB:22:1:051
9.
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 http://dx.doi.org/10.1387/ijdb.041811af
10.
J.M. Holopainen,J.A. Moilanen,T. Sorsa
Activation of matrix metalloproteinase-8 by membrane type 1-MMP and their expression in human tears after photorefractive keratectomy
Invest Ophthalmol Vis Sci, 44 (2003), pp. 2550-2556
11.
V. Knauper,H. Will,C. Lopez-Otin
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
12.
P. Maisi,K. Prikk,R. Sepper
Soluble membrane-type 1 matrix metalloproteinase (MT1-MMP) and gelatinase A (MMP-2) in induced sputum and bronchoalveolar lavage fluid of human bronchial asthma and bronchiectasis
APMIS, 110 (2002), pp. 771-782
13.
L.M. Wright,W. Maloney,X. Yu,L. Kindle,P. Collin-Osdoby,P. Osdoby
Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts
14.
A.M. Havens,E. Chiu,M. Taba
Stromal-derived factor-1alpha (CXCL12) levels increase in periodontal disease
J Periodontol, 79 (2008), pp. 845-853 http://dx.doi.org/10.1902/jop.2008.070514
15.
H.M. Lee,L.M. Golub,J. Cao
CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer
Curr Med Chem, 8 (2001), pp. 257-260
16.
P. Mantyla,M. Stenman,D. Kinane
Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8- specific chairside test
J Periodontal Res, 41 (2006), pp. 503-512 http://dx.doi.org/10.1111/j.1600-0765.2006.00897.x
17.
P. Mantyla,M. Stenman,D.F. Kinane
Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis
J Periodontal Res, 38 (2003), pp. 436-439
18.
T. Sorsa,P. Mantyla,H. Ronka
Scientific basis of a matrix metalloproteinase-8 specific chair-side test for monitoring periodontal and peri-implant health and disease
Ann N Y Acad Sci, 878 (1999), pp. 130-140
19.
M. Hernandez,B. Martinez,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 http://dx.doi.org/10.1111/j.1600-051X.2007.01107.x
20.
M. Hernández,M.A. Valenzuela,C. Lopez-Otin
Matrix metalloproteinase-13 is highly expressed in destructive periodontal disease activity
J Periodontol, 77 (2006), pp. 1863-1870 http://dx.doi.org/10.1902/jop.2006.050461
21.
A.D. Haffajee,S.S. Socransky,J.M. Goodson
Comparison of different data analyses for detecting changes in attachment level
J Clin Periodontol, 10 (1983), pp. 298-310
22.
T. Sorsa,L. Tjaderhane,Y.T. Konttinen
Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation
Ann Med, 38 (2006), pp. 306-321 http://dx.doi.org/10.1080/07853890600800103
23.
H. Birkedal-Hansen
Role of matrix metalloproteinases in human periodontal diseases
J Periodontol, 64 (1993), pp. 474-484 http://dx.doi.org/10.1902/jop.1993.64.5s.474
24.
S. Villalba,O. Salvucci,Y. Aoki
Serum inactivation contributes to the failure of stromalderived factor-1 to block HIV-I infection in vivo
J Leukoc Biol, 74 (2003), pp. 880-888 http://dx.doi.org/10.1189/jlb.0403149
25.
T. Sorsa,L. Tjaderhane,T. Salo
Matrix metalloproteinases (MMPs) in oral diseases
26.
T. Ingman,T. Sorsa,J. Michaelis,Y.T. Konttinen
Matrix metalloproteinases-1 -3, and -8 in adult periodontitis in situ. An immunohistochemical study
Ann N Y Acad Sci, 732 (1994), pp. 459-461
27.
L.M. Golub,T. Sorsa,H.M. Lee
Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva
J Clin Periodontol, 22 (1995), pp. 100-109
28.
T. Ingman,T. Tervahartiala,Y. Ding
Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients
J Clin Periodontol, 23 (1996), pp. 1127-1132
29.
D.V. Rozanov,A.Y. Strongin
Membrane type-1 matrix metalloproteinase functions as a proprotein self-convertase Expression of the latent zymogen in Pichia pastoris, autolytic activation, and the peptide sequence of the cleavage forms
J Biol Chem, 278 (2003), pp. 8257-8260 http://dx.doi.org/10.1074/jbc.M213246200
30.
G.A. McQuibban,G.S. Butler,J.H. Gong
Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1
J Biol Chem, 276 (2001), pp. 43503-43508 http://dx.doi.org/10.1074/jbc.M107736200
31.
S. Singh,U.P. Singh,W.E. Grizzle,J.W. Lillard Jr.
CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion
Lab Invest, 84 (2004), pp. 1666-1676 http://dx.doi.org/10.1038/labinvest.3700181
32.
P.A. Hill,A.J. Docherty,K.M. Bottomley
Inhibition of bone resorption in vitro by selective inhibitors of gelatinase collagenase
Biochem J, 308 (1995), pp. 167-175
33.
P.A. Hill,G. Murphy,A.J. Docherty
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

 

CORRESPONDENCIA AUTOR
Marcela Hernández.
mhernandezrios@gmail.com

Trabajo recibido el 09/06/2009.
Aprobado para su publicación el 05/08/2009.

Copyright © 2009.
Sociedad de Periodoncia de Chile, Sociedad de Implantología Oral de Chile y Sociedad de Prótesis y Rehabilitación Oral de Chile.