Tumor Necrosis Factor‐α and Porphyromonas gingivalis Lipopolysaccharides Decrease Periostin in Human Periodontal Ligament Fibroblasts

Abstract

Background: Periostin is a matricellular protein essential for tissue integrity and maturation and is believed to have a key function as a modulator of periodontal ligament (PDL) homeostasis. The aim of this study is to evaluate whether periodontal disease‐associated pathogen‐related virulence factors (endotoxins/lipopolysaccharides [LPS]) and proinflammatory cytokines alter the expression of periostin in PDL cells.Methods: Human PDL cultures were exposed to inflammatory mediators (tumor necrosis factor‐α [TNF‐α]), bacterial virulence factors (Porphyromonas gingivalis LPS) or a combination in a biomechanically challenged environment. Culture conditions were applied for 24 hours, 4 days, and 7 days. Periostin and TGF‐β inducible gene clone H3 (βIGH3) mRNA expression from cell lysates were analyzed. Periostin and βIGH3 proteins were also detected and semiquantified in both cell lysates and cell culture supernatants by Western blot. In addition, periostin localization by immunofluorescence was performed. Analysis of variance and Fisher tests were used to define the statistical differences among groups (P <0.05).Results: In a mechanically challenged environment, periostin protein was more efficiently incorporated into the matrix compared to the non‐loaded controls (higher levels of periostin in the supernatant in the non‐loaded group). Interestingly, chronic exposure to proinflammatory cytokines and/or microbial virulence factors significantly decreased periostin protein levels in the loaded cultures. There was greater variability on βIGH3 levels, and no particular pattern was clearly evident.Conclusions: Inflammatory mediators (TNF‐α) and bacterial virulence factors (P. gingivalis LPS) decrease periostin expression in human PDL fibroblasts. These results support a potential mechanism by which periostin alterations could act as a contributing factor during periodontal disease progression.

Inflammatory microenvironment and tumor necrosis factor alpha as modulators of periostin and CCN2 expression in human non-healing skin wounds and dermal fibroblasts

“…The micro-environmental factors present within the damaged tissue have been well characterized and several groups have documented elevated TNFα levels in non-healing skin wound fluid [29][30][31]. Moreover, the anti-fibrotic influence of TNFα through suppression of TGFβ signaling is well documented [32][33][34][35]. We have shown here that non-healing wounds contain significant neutrophil infiltration and TNFα immunoreactivity in the wound bed, which has also been reported previously in pressure sores [36].…”

Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway

“…We first examined Periostin production and secretion by epithelial and mesenchymal cells. Using a human keratinocyte cell line (NOK-SI) [18] and a primary culture of human fibroblasts (hPDL) [30], we found that both cell types produced Periostin (Figure 2A). Full length Periostin is a 93 kDa protein, and additional human Periostin isoforms range from 83 kDa to 87 kDa (from UniProtKB/Swiss-Prot database - Q15063).…”

Differential expression of periostin, sclerostin, receptor activator of nuclear factor‐κB, and receptor activator of nuclear factor‐κB ligand genes in severe chronic periodontitis

“…Gingival fibroblasts and periodontal ligament cells produce POSTN only when stimulated by interleukin (IL)‐13 and IL‐14 cytokines, while TNF‐α and Porphyromonas gingivalis lipopolysaccharides (LPS) did not induce POSTN production . Moreover, in a study on fibroblasts stimulated with TNF‐α and Porphyromonas gingivalis LPS, a decreased expression of POSTN was noted . A ligature‐induced periodontitis model in rats demonstrated the downregulation of POSTN in sites with chronic periodontal inflammation.…”