Role of fibroblast populations in peri-implantitis.
OBJECTIVE
To understand the contribution of stromal cells, such as granulation tissue fibroblasts, to peri-implantitis with regard to (1) the secretion of constitutive factors promoting migration/survival of infiltrates into osseointegrated sites; and (2) the effect of exogenous infiltrate cytokines on the cells' secretion.


METHODS
Fibroblasts were cultured from eight peri-implantitis sites. Multiplexed enzyme-linked immunosorbent assay was used to quantify factors secreted by the cells either unstimulated or stimulated with gamma interferon (IFN gamma), interleukin 4 (IL4), or tumor necrosis factor alpha (TNF alpha). Controls consisted of fibroblasts cultured from healthy gingival and chronic periodontitis granulation tissues.


RESULTS
Peri-implantitis fibroblasts differed significantly from periodontitis fibroblasts in their reduced secretion of the collagen inducer transforming growth factor beta-1 (TGF beta 1) and tissue inhibitor of metalloproteinase-1. The cells exhibited enhanced secretion of angiogenic factor vascular endothelial growth factor (VEGF) and collagenolytic matrix metalloproteinase 1 (MMP1) compared to both healthy and periodontitis fibroblasts. Fibroblasts from both periodontitis and peri-implantitis sites exhibited a pronounced proinflammatory profile compared to normal gingival fibroblasts with respect to secretion of chemokines IL6, IL8, and monocyte chemoattractant protein 1 (MCP1). Fibroblasts stimulated with TNF alpha showed increased levels of IL6, IL8, MCP1; neutrophil chemokine growth-related oncogene alpha stimulation with IFN gamma increased MCP1; and stimulation with IL4 increased VEGF.


CONCLUSIONS
The results indicate that peri-implantitis fibroblasts represent a distinct stromal population. The cells might participate in the pathogenesis of peri-implantitis by up-regulating both vascularity and matrix breakdown, thus promoting migration/maintenance of infiltrates into the site. Cytokines produced by infiltrates could enhance the inflammatory nature of the cells in a self-feeding loop.
Bordin
Sandra
S
Department of Periodontics, Mail Box 357444, University of Washington, Seattle, WA 98195-7444, USA. bordin@u.washington.edu
Flemmig
Thomas F
TF
Verardi
Simone
S
D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D015921:Dental Implants / Q000009:adverse effects*; D005347:Fibroblasts / Q000145:classification / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000276:immunology; D006801:Humans; D010518:Periodontitis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D012016:Reference Values; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D015921:Dental Implants; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A