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

AIM: Circular RNAs (circRNAs) have been identified as key regulators in inflammatory diseases, yet their function in pulpitis is unclear. This study investigates their potential role in the progression of pulpitis. METHODOLOGY: Microarray and single-cell RNA sequencing were applied to assess DNA damage responses (DDR) in inflammatory pulp and its derived stem cells, respectively. qRT-PCR and Western blot were employed to detect the DNA double-strand break (DSB) marker γ-H2AX and inflammatory cytokines in pulp tissue. Bioinformatics analysis was used to identify upregulated circRNAs in inflamed DPSCs. Functional assays were performed to assess the impact of circ_0042103 on LPS-driven cellular damage and inflammation in DPSCs. The interaction between circ_0042103 and TAF15 was investigated using RNA FISH, pulldown, and nuclear-cytoplasmic fractionation assays. Transfection with circ_0042103/TAF15-siRNA in DPSCs was carried out to evaluate activation of the nucleotide excision repair (NER) pathway and its regulatory effects on DNA damage and inflammation. RESULTS: DDR was activated in both pulpitis and inflamed DPSCs. DNA damage showed a positive correlation with inflammation in pulpitis. In vitro, circ_0042103 upregulation amplified LPS-stimulated DDR and inflammatory signaling, whereas its knockdown alleviated both effects. Mechanistically, circ_0042103 bound TAF15, leading to decreased levels of the NER-related proteins (ERCC1 and PCNA) and increased DNA damage and inflammation. CONCLUSION: By interacting with TAF15, circ_0042103 reduces the levels of the NER-related proteins ERCC1 and PCNA, leading to increased DNA damage and inflammation in hDPSCs, thereby defining a circ_0042103/TAF15/NER axis in pulpitis progression.