Fibroblast VEGF‐receptor 1 expression as molecular target in periodontitis

Abstract

Based on the finding that VEGF-receptor kinase inhibition impaired collagen degradation pathways, Flt-1 may represent a candidate for therapeutic approaches in periodontitis.

Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis

“…Three pairs of patient-matched gingival fibroblasts were isolated from periodontitis-affected and healthy gingival tissues, and designated as periodontitis-associated fibroblasts (PAFs) and non-periodontitis-associated fibroblasts (non-PAFs). Consistent with our previous report 7 , PAFs induced collagen degradation more strongly than non-PAFs in an established three-dimensional co-culture model of periodontitis ( Fig. 4(a) ).…”

“…Gingival fibroblasts play important roles not only in the homeostasis of gingival tissue architecture but also in the pathogenesis of periodontitis 2 . Recently, we isolated and characterized a subset of gingival fibroblasts derived from periodontitis-affected patients that were designated as periodontitis-associated fibroblasts (PAFs), and demonstrated that they were highly capable of collagen degradation 6 7 .…”

“…Preventing ECM degradation in supportive connective tissues for the tooth seems a straightforward therapeutic approach for periodontitis. As a proof of concept, we have previously demonstrated that targeting PAFs by inhibition of key signaling pathways, i.e., transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF), successfully protected PAF-mediated degradation of collagen in experimental models of periodontitis 6 7 . Obviously, it is important to elucidate the PAF phenotype from diagnostic and therapeutic viewpoints; however, the molecular mechanisms how PAFs appear and contribute to ECM degradation in the periodontitis tissues are largely unknown.…”

“…As part of the FANTOM5 project, we performed CAGE analyses on primary cultured human gingival fibroblasts, periodontal ligament fibroblasts, gingival epithelial cells, and epithelial cell rests of Malassez 11 . Furthermore, CAGE profiles of PAFs were also examined together with patient-matched gingival fibroblasts derived from healthy gingival tissues, helping us to identify specific molecular features and novel markers that are potentially of functional relevance 7 .…”

Optimized Platelet‐Rich Fibrin With the Low‐Speed Concept: Growth Factor Release, Biocompatibility, and Cellular Response

“…Another interesting area of research that is often left unstudied is the effect of higher‐than‐optimal doses of growth factors on tissue remodeling. For instance, Ohshima et al 35 , 36 found certain growth factors, including TGF‐β and VEGF, are not only capable of supporting tissue regeneration but may also participate in tissue degradation in periodontitis. While in general both of these growth factors are routinely associated with tissue regrowth (TGF‐β) and angiogenesis (VEGF), it must not be excluded that they may also show negative effects.…”