The circ_0042103/TAF15/NER axis regulates inflammation and DNA damage in pulpitis.

Area of Science:

• Molecular Biology
• Dental Research
• Immunology

Background:

• Circular RNAs (circRNAs) are implicated in inflammatory diseases.
• The role of circRNAs in pulpitis, a dental inflammatory condition, remains largely unknown.
• Understanding these roles is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the function of circRNAs in pulpitis progression.
• To identify specific circRNAs involved in the inflammatory process.
• To elucidate the molecular mechanisms underlying circRNA regulation in pulpitis.

Main Methods:

• Microarray and single-cell RNA sequencing to analyze DNA damage responses (DDR) in pulpitis.
• qRT-PCR and Western blot to quantify DNA damage markers and inflammatory cytokines.
• Functional assays to assess the impact of circ_0042103 on cellular damage and inflammation.
• RNA FISH, pulldown, and fractionation assays to study circRNA-protein interactions.
• siRNA-mediated knockdown to evaluate the role of circ_0042103 and TAF15 in DNA repair pathways.

Main Results:

• DNA damage responses (DDR) were activated in pulpitis, correlating positively with inflammation.
• Upregulated circ_0042103 exacerbated lipopolysaccharide (LPS)-induced DDR and inflammation in dental pulp stem cells (DPSCs).
• Circ_0042103 interacted with TAF15, reducing levels of nucleotide excision repair (NER) proteins (ERCC1, PCNA), thereby increasing DNA damage and inflammation.

Conclusions:

• Circ_0042103 promotes pulpitis by interacting with TAF15, which downregulates ERCC1 and PCNA.
• This interaction impairs DNA repair, leading to increased DNA damage and inflammation in human dental pulp stem cells (hDPSCs).
• A novel circ_0042103/TAF15/NER axis is identified as a key player in pulpitis pathogenesis.