In Vitro Bioassay for Damage-Associated Molecular Patterns Arising from Injured Oral Cells

Layla Panahipour ¹, Chiara Micucci ¹, Benedetta Gelmetti ¹

⁰Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

Bioengineering (basel, Switzerland) +

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July 27, 2024

View abstract on PubMed

Summary

Oral cell damage signals activate gingival fibroblasts, increasing specific gene expression. This gene panel can assess oral material biocompatibility and damage-associated molecular patterns in periodontitis research.

Area Of Science

Oral biology and cell signaling
Periodontal disease mechanisms
Biomaterial biocompatibility testing

Background

Gingival fibroblasts produce paracrine signals vital for periodontal homeostasis and disease, including periodontitis and oral cancers.
Key paracrine signals include stanniocalcin-1 (STC1), amphiregulin (AREG), C11orf96, and prostaglandin E synthase (PTGES).
Injury-induced damage-associated molecular patterns (DAMPs) may trigger increased gene expression in fibroblasts.

Purpose Of The Study

To establish a gene expression panel in gingival fibroblasts as a bioassay for damage-associated activity.
To investigate the response of gingival fibroblasts to lysates from various oral cell types.
To evaluate the role of TGF-β signaling in mediating fibroblast responses to damage signals.

Main Methods

Gingival fibroblasts were exposed to cell lysates from oral squamous cell carcinoma lines (TR146, HSC2), oral epithelial cells, and gingival fibroblasts.
Gene transcription levels of STC1, AREG, C11orf96, and PTGES were measured.
Protein levels of STC1 were assessed, and the effect of TGF-β receptor 1 kinase inhibition (SB431542) was evaluated.

Main Results

All tested oral cell lysates significantly upregulated the transcription of the entire gene panel, with STC1 also increased at the protein level.
Inhibition of TGF-β receptor 1 kinase partially reduced STC1, AREG, and C11orf96 expression but increased PTGES expression.
These findings indicate that damage signals from oral cells alter gingival fibroblast paracrine activity.

Conclusions

Oral cell-derived damage signals modulate the paracrine function of gingival fibroblasts.
The investigated gene expression panel serves as a potential bioassay for assessing the biocompatibility of oral materials.
This approach offers a novel method for evaluating damage-associated molecular patterns in oral health research.

Keywords:

AREG C11orf96 DAMPs STC1 alarmins gingival fibroblast injured oral epithelial cells necrosis oral squamous carcinoma cells periodontitis