CircPVT1 promotes periodontitis progression by regulating miR-24-3p/HIF1AN pathway

Abstract

Purpose and background: Periodontitis is a chronic inflammatory oral disease affecting half of the adult population. Circular RNA plays a critical role in periodontitis. CircPVT1(hsa_circ_0085536) was abundant in periodontitis tissues and cells but its mechanism are still unclear. We aim to explore the role of circPVT1 in periodontitis and elucidate how circPVT1 acts.

Methods: Gingival tissues from patients with periodontitis(n=20) and health participants(n=20) were collected and the expression of circPVT1 was measured by realtime quantitative PCR(RT-qPCR). Cell model for periodontitis was performed by PDLCs treated lipopolysaccharide(LPS). Cell Counting Kit-8(CCK-8), flow cytometry, enzyme-linked immunoabsorbent assay (ELISA), ALP staining and Alizarin red staining were conducted to detect cell viability, apoptosis, inflammatory and oxidative stress factors and osteogenic differentiation. The targeting microRNA(miRNA)/mRNA axis of circPVT1 was predicted and screened.

Results: circPVT1 was upregulated in the gingival tissues of patients with periodontitis. Silencing of circPVT1 inhibited cell viability, decreased inflammatory factors(IL-1β, TNF-α, IL-6) and oxidative stress factors, activated NRF-2 and HO-1 expression and promoted apoptosis and osteoclast differentiation in PDLCs after treated LPS. However, these effects were reversed by transfected miR-24-3p inhibitor and overexpressed of hypoxia-inducible factor 1 subunit alpha inhibitor(HIF1AN) in PDLCs.

Conclusion: circPVT1 promotes the progression of periodontitis by modulating NRF-2/HO-1 pathway via the miR-24-3p/HIF1AN axis.

Keywords: HIF1AN; Inflammation; Oxidative stress; Periodontitis; circPVT1; miR-24–3p.