Matrix metalloproteinases regulate extracellular levels of SDF-1/CXCL12, IL-6 and VEGF in hydrogen peroxide-stimulated human periodontal ligament fibroblasts.
Periodontitis is a highly prevalent infectious disease characterized by the progressive inflammatory destruction of tooth-supporting structures, leading to tooth loss. The underling molecular mechanisms of the disease are incompletely understood, precluding the development of more efficient screening, diagnostic and therapeutic approaches. We investigated the interrelation of three known effector mechanisms of the cellular response to periodontal infection, namely reactive oxygen species (ROS), matrix metalloproteinases (MMPs) and cytokines in primary cell cultures of human periodontal ligament fibroblast (hPDLF). We demonstrated that ROS increase the activity/levels of gelatinolytic MMPs, and stimulate cytokine secretion in hPDLF. Additionally, we proved that MMPs possesses immune modulatory capacity, regulating the secreted levels of cytokines in ROS-stimulated hPDLF cultures. This evidence provides further insight in the molecular pathogenesis of periodontitis, contributing to the future development of more effective therapies.
Conservative Dentistry Department, Faculty of Dentistry Universidad de Chile, Santiago, Chile; Laboratory of Periodontal Biology, Faculty of Dentistry Universidad de Chile, Santiago, Chile.
Franco
F
Cavalla
Conservative Dentistry Department, Faculty of Dentistry Universidad de Chile, Santiago, Chile.
Constanza
C
Osorio
Escuela Medicina Veterinaria, Facultad de Ecología y Recursos Naturales, Universidad Andrés Bello, Santiago, Chile.
Rodolfo
R
Paredes
Biochemistry and Molecular Biology Department, Faculty of Chemical and Pharmaceutical Sciences Universidad de Chile, Santiago, Chile.
María Antonieta
MA
Valenzuela
Laboratory of Periodontal Biology, Faculty of Dentistry Universidad de Chile, Santiago, Chile.
Jocelyn
J
García-Sesnich
Institute of Dentistry University of Helsinki, Helsinki, Finland; Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland; Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
Timo
T
Sorsa
Institute of Dentistry University of Helsinki, Helsinki, Finland.
Taina
T
Tervahartiala
Laboratory of Periodontal Biology, Faculty of Dentistry Universidad de Chile, Santiago, Chile; Oral Pathology Department, Faculty of Dentistry, Universidad de Chile, Santiago, Chile. Electronic address: mhernandezrios@gmail.com.
Marcela
M
Hernández
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology*; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000975:Antioxidants; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D006877:Hydroxamic Acids; C508600:IL6 protein, human; D007211:Indoles; D015850:Interleukin-6; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin; D006861:Hydrogen Peroxide; D020782:Matrix Metalloproteinases; C119203:ilomastat
Cytokines; Matrix metalloproteinases; Oxidative stress; Periodontal ligament fibroblast