Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in various physiological and pathobiological processes, including DNA methylation, histone modification, RNA post-transcriptional regulation and protein translation regulation(Ruan et al., 2022; Shabna et al., 2023; Zhu et al., 2020). For example, lncRNA Opa interacting protein 5-antisense RNA 1(OIP5-AS1) inhibits the LPS (lipopolysaccharide)-induced inflammatory response and promotes human periodontal ligament stem cell (hPDLSC) osteogenesis by sponging miR-92a-3p(Wang & Duan, 2022). Shu et al. reported that lncRNA UCA1 inhibits LPS-managed inflammatory injury via deactivation of the miR-499b-5p/TLR4 axis(Zhao et al., 2021). In addition, Shu et al. demonstrated that lncRNA UCA1 promotes chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via miRNA-124–3p/SMAD4 and miRNA-145–5p/SMAD5 axis(Shu et al., 2019). LncRNA XIST (X inactive specific transcript) is involved in osteogenic differentiation of hPDLSCs through absorbing miR-214–3p(Feng et al., 2020). However, whether lncRNA UCA1 plays a role in the osteogenic differentiation of hPDLSCs and its molecular mechanism remains unclear.

The complex and precise regulatory functions of lncRNAs in gene expression and physical development partly explain the puzzle of genomic complexity. Previous studies have indicated that lncRNAs are involved in a variety of crucial cell biological activities by regulating pre - and post- transcriptional gene expression(Liu et al., 2020; Luaibi et al., 2023). Currently, various lncRNAs have been validated closely related to osteogenic differentiation of hPDLSCs. Xu et al.(Xu et al., 2019) claimed that lncRNA- TWIST1 (Twist family bHLH transcription factor 1) promotes osteogenic differentiation of hPDLSCs by suppressing TWIST1 expression. In addition, lncRNA ANRIL (INK4 locus) mediates the miR-7–5p/IGF-1R axis to regulate osteogenic differentiation of hPDLSCs(Bian et al., 2021). Interestingly, it was claimed that the lncRNA UCA1 promotes differentiation of BMSCs or cancer stem cells by sponging miRNAs (Gao et al., 2021, Shu et al., 2019). However, other scholars have demonstrated that inhibiting lncRNA UCA1 can activate the BMP-2/(Smad1/5/8) signaling pathway to promote the proliferation and differentiation in osteoblasts(Zhang et al., 2019). Consequently, the underlying effect and mechanism of UCA1 in hPDLSC osteogenesis require further exploration.

Studies have shown that miRNAs play crucial roles in the regulation of cell growth and development. Alterations in miRNA are involved in bone remodeling(Ko et al., 2020). Liu et al. claimed that miR-96 promotes BMSCs osteoblast differentiation and further mediates bone metabolism by targeting osterix (Osx) and activating Wnt signaling pathways(Liu et al., 2018). Bioinformatics and in vitro experiments validated the binding site between miR-96–5p and the Osx 3′ UTR(Zang et al., 2022). Therefore, in this study, we proposed the hypothesis that the lncRNA UCA1 sponge adsorbed miR-96–5p to regulate the osteogenic differentiation of hPDLSCs. We elaborated the molecular mechanism of UCA1 in regulating osteogenic differentiation of hPDLSCs and provided a theoretical basis for exploring feasible targets for the treatment of periodontitis.