TiOnanotubes (TNTs) significantly promote osteogenic differentiation and bone regeneration of cells. Nevertheless, the biological processes by which they promote osteogenesis are currently poorly understood. Long non-coding RNAs (lncRNAs) are essential for controlling osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Epigenetic chromatin modification is one of the pathways in which lncRNAs regulate osteogenic differentiation. Here, we reported that TNTs could upregulate lncRNA, and inhibition of lncRNAin human BMSCs (hBMSCs) grown on TNTs could decrease runt-related transcription factor 2 (RUNX2), alkaline phosphatase, osteopontin, and osteocalcin (OCN) expression. Furthermore, we discovered that inhibiting lncRNAelevated the expression of lncRNA, and lncRNAknockdown promoted osteogenic differentiation in hBMSCs. RNA immunoprecipitation experiments showed that lncRNAcould interact with EZH2 to induce H3K27 methylation in the promoter regions of RUNX2 and OCN, suppressing gene expression epigenetically. According to these results, lncRNAis upregulated by TNTs to promote osteogenic differentiation through/EZH2-mediated epigenetic modifications.
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