Comprehensive analysis of the long noncoding RNA-associated competitive endogenous RNA network in the osteogenic differentiation of periodontal ligament stem cells

Abstract

Backgroud The mechanism implicated in the osteogenesis of human periodontal ligament stem cells (PDLSCs) has been investigated for years. Previous genomics data analyses showed that long noncoding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) have significant expression differences between induced and control human PDLSCs. Competing for endogenous RNAs (ceRNA), as a widely studied mechanism in regenerative medicine, while rarely reported in periodontal regeneration. The key lncRNAs and their ceRNA network might provide new insights into molecular therapies of periodontal regeneration based on PDLSCs. Results Two networks reflecting the relationships among differentially expressed RNAs were constructed. One ceRNA network was composed of 6 upregulated lncRNAs, 280 upregulated mRNAs, and 18 downregulated miRNAs. The other network contained 33 downregulated lncRNAs, 73 downregulated mRNAs, and 5 upregulated miRNAs. Functional analysis revealed that 38 GO terms and 8 pathways related with osteogenesis were enriched. Twenty-four osteogenesis-related gene-centred lncRNA-associated ceRNA networks were successfully constructed. Among these pathways, we highlighted MAPK and TGF-beta pathways that are closely related to osteogenesis. Subsequently, subnetworks potentially linking the GO:0001649 (osteoblast differentiation), MAPK and TGF-beta pathways were constructed. The qRT-PCR validation results were consistent with the microarray analysis. Conclusion We construct a comprehensively identified lncRNA-associated ceRNA network might be involved in the osteogenesis of PDLSCs, which could provide insights into the regulatory mechanisms and treatment targets of periodontal regeneration.

The signaling pathways involved in non‐coding RNA regulation during osteogenic differentiation of periodontal tissue‐derived cells in the field of periodontitis

“…Zheng et al 14 identified over 200 differentially expressed ln-cRNAs in PDLSCs during osteogenic differentiation at 3, 7, and 14 days, and another 14 mRNA and 8 lncRNA expression profiles were time-dependent. In a similar study, Lai et al 16 discovered 994 upregulated lncRNAs, 1578 upregulated mRNAs, and 30 upregulated miRNAs, as well as 1177 downregulated lncRNAs, 1979 downregulated mRNAs, and 86 downregulated miRNAs in PDLSCs following osteogenic induction. Further analysis revealed the involvement of MAPK and TGF-β signaling pathways in the osteogenic differentiation of PDLSCs.…”

“…A growing body of evidence has shown that numerous ncRNAs were closely associated with the osteogenic differentiation of periodontal tissue-derived cells and were involved in multiple signaling pathways, including the Wnt, BMP/Smad, NF-κB, and PI3-K/Akt/mTOR pathways. [11][12][13][14][15][16][17][18] In this review, we summarized these signaling pathways that ncRNAs regulate in osteogenic differentiation of periodontal tissue-derived cells, providing new ideas for the future treatment of periodontitis and periodontal regeneration (Figure 1).…”

“…Non‐coding RNAs (ncRNAs) are a type of RNA that does not have protein‐coding functions but can regulate various physiological processes, such as gene regulation, chromatin remodeling, RNA processing, and protein synthesis. A growing body of evidence has shown that numerous ncRNAs were closely associated with the osteogenic differentiation of periodontal tissue‐derived cells and were involved in multiple signaling pathways, including the Wnt, BMP/Smad, NF‐κB, and PI3‐K/Akt/mTOR pathways 11–18 . In this review, we summarized these signaling pathways that ncRNAs regulate in osteogenic differentiation of periodontal tissue‐derived cells, providing new ideas for the future treatment of periodontitis and periodontal regeneration (Figure 1).…”

Epigenetic regulation of odontogenic stem cells and their application in pulp and periodontal regeneration

“…By inhibiting the expression of miRNAs, lncRNAs can also play a regulatory role. During the osteogenic differentiation of PDLSCs, lncRNAs can act as ceRNAs and form networks to regulate the Wnt/β-catenin signaling pathway 97 . lncRNA-ANCR competitively binds miR-758 and inhibits the expression of Notch2, which further affects the Wnt/β-catenin signaling pathway and inhibits the osteogenic differentiation of PDLSCs 98 .…”

Non-coding RNA delivery for bone tissue engineering: Progress, challenges, and potential solutions

“…As the complex regulatory mechanisms of lncRNAs and their biological functions are not fully understood, more studies have concentrated on using vectors to deliver small ncRNAs for bone defect repair. However, several recent studies have shown that lncRNAs can affect the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through a mechanism known as competing endogenous RNAs (ceRNAs), which has received increasing attention (Hong et al, 2020;Lai et al, 2022;Wang et al, 2020b. The experimental results of Ouyang et al (2020) showed that lncRNA ENST00000563492 can act as a ceRNA for miR-205-5p to upregulate the expression of CDH11 and VEGF, thereby promoting the osteogenic differentiation of BMSCs.…”