PRMT5 inhibition ameliorates inflammation and promotes the osteogenic differentiation of LPS‑induced periodontal stem cells via STAT3/NF‑κB signaling

Kun Zhang; Changshun Li; Jian Sun; Xiaobei Tian

doi:10.3892/etm.2023.11963

PRMT5 inhibition ameliorates inflammation and promotes the osteogenic differentiation of LPS‑induced periodontal stem cells via STAT3/NF‑κB signaling

Exp Ther Med. 2023 Apr 19;25(6):264. doi: 10.3892/etm.2023.11963. eCollection 2023 Jun.

Authors

Kun Zhang^{1

2}, Changshun Li^{1

2}, Jian Sun^{1

2}, Xiaobei Tian^{1

2}

Affiliations

¹ Department of Cariology and Endodontics, The Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.
² School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.

Abstract

It has been reported that protein arginine methyltransferase 5 (PRMT5) serves a significant role in osteogenic differentiation and inflammatory response. Nevertheless, its role in periodontitis as well as its underlying mechanism remain to be elucidated. The aim of the present study was to explore the role of PRMT5 in periodontitis and whether PRMT5 could reduce liposaccharide (LPS)-induced inflammation of human periodontal ligament stem cells (hPDLSCs) and promote osteogenic differentiation through STAT3/NF-κB signaling. In the current study, the expression levels of PRMT5 were determined in LPS-induced hPDLSCs by reverse transcription-quantitative PCR and western blot analysis. ELISA and western blot analysis were employed to assess the secretion and expression levels of inflammatory factors, respectively. The osteogenic differentiation and mineralization potential of hPDLSCs were evaluated using alkaline phosphatase (ALP) activity assay, Alizarin red staining and western blot analysis. Additionally, western blot analysis was applied to determine the expression levels of the STAT3/NF-κB signaling pathway-related proteins. The results showed that the expression levels of PRMT5 were significantly enhanced in LPS-induced hPDLSCs. Additionally, PRMT5 knockdown reduced the contents of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase and cyclooxygenase-2. PRMT5 depletion also enhanced ALP activity, improved the mineralization ability and upregulated bone morphogenetic protein 2, osteocalcin and runt-related transcription factor 2 in LPS-induced hPDLSCs. Furthermore, PRMT5 knockdown inhibited inflammation and promoted the osteogenic differentiation of hPDLSCs via blocking the activation of the STAT3/NF-κB signaling pathway. In conclusion, PRMT5 inhibition suppressed LPS-induced inflammation and accelerated osteogenic differentiation in hPDLSCs via regulating STAT3/NF-κB signaling, thus providing a potential targeted therapy for the improvement of periodontitis.

Keywords: STAT3/NF-κB signaling; human periodontal ligament stem cells; osteogenic differentiation; periodontitis; protein arginine methyltransferase 5.

Grants and funding

Funding: No funding was received.