Abstract
Periodontitis is a chronic inflammatory disease leading to progressive connective tissue degradation and loss of the tooth-supporting bone. Clinical and experimental studies suggest that hepatocyte growth factor (HGF) is involved in the dysregulated fibroblast–epithelial cell interactions in periodontitis. The aim of this study was to explore effects of HGF to impact fibroblast-induced collagen degradation. A patient-derived experimental cell culture model of periodontitis was applied. Primary human epithelial cells and fibroblasts isolated from periodontitis-affected gingiva were co-cultured in a three-dimensional collagen gel. The effects of HGF neutralizing antibody on collagen gel degradation were tested and transcriptome analyses were performed. HGF neutralizing antibody attenuated collagen degradation and elicited expression changes of genes related to extracellular matrix (ECM) and cell adhesion, indicating that HGF signaling inhibition leads to extensive impact on cell–cell and cell–ECM interactions. Our study highlights a potential role of HGF in periodontitis. Antagonizing HGF signaling by a neutralizing antibody may represent a novel approach for periodontitis treatment.
Highlights
Periodontitis is a chronic inflammatory process associated with loss of the tooth-supporting tissue [1, 2]
To develop an experimental model of periodontitis, primary cultured gingival epithelial cells and periodontitis-associated fibroblasts (PAFs) were co-cultured in collagen gels, which appears to recapitulate epithelial
In a series of previous reports, we have demonstrated that PAFs display a remarkably higher capacity of extracellular matrix (ECM) degradation compared to normal fibroblasts [9, 18]
Summary
Periodontitis is a chronic inflammatory process associated with loss of the tooth-supporting tissue [1, 2]. Degradation of extracellular matrix (ECM) within the gingival connective tissue located between tooth and alveolar bone is the driving force in the pathological process of periodontitis [9, 17,18,19,20]. We have isolated periodontitis-associated fibroblasts (PAFs) from the gingiva of periodontitis affected patients. These PAFs demonstrated a higher capacity of collagen degradation compared to normal gingival fibroblast and were characterized by a distinct gene expression profile [8, 9, 18]. To develop an experimental model of periodontitis, primary cultured gingival epithelial cells and PAFs were co-cultured in collagen gels, which appears to recapitulate epithelial
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