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

Abstract

Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.

Host‐microbe interactions: Profiles in the transcriptome, the proteome, and the metabolome

“…18 Human fibroblasts have also been analyzed in transcriptomic studies of periodontitis, providing a more comprehensive overview of periodontitis-related fibroblast transcriptomes. 11…”

Extracellular Matrix in Secondary Palate Development

“…Naturally, mutations affecting the function of these transcription factors would affect the integrity of the ECM by altering its composition. Most of the transcription factors included on the list fall in this category, often regulating directly the expression of collagen, fibronectin, or cadherin genes (Bi et al, ; Hsieh et al, ; Cho et al, ; Papangeli and Scambler, ; Simental‐Mendia et al, ; Horie et al, ; Yoh et al, ). Transcriptional control might be contextual as seen with the Saethre–Chotzen gene TWIST1 (101400) that can both upregulate and downregulate collagen expression (Fang et al, ; Garcia‐Palmero et al, ).…”

Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical trial)

“…It was reported that GF cultured in osteogenic media differentiated into osteoblasts . An appropriate ECM signal can direct GF to form hard tissue through expression of mRNA for alkaline phosphatase and bone morphogenetic protein 2/4 (BMP2/4) . In addition, it has been reported that each fibroblast culture contains a small proportion of mesenchymal stem cells (MSCs) without undergoing an enrichment selection procedure .…”