The multipotent and easily accessible characteristics of dental pulp stem cells (DPSCs) make them a promising target for bone tissue engineering. Long non‑coding RNAs (lncRNAs) have an important role in the osteogenic differentiation of mesenchymal stem cells. Nevertheless, whether lncRNAs are involved in the osteogenic differentiation of DPSCs remains unclear. The present study examined the expression alterations of lncRNAs in tumor necrosis factor‑α induced osteogenic differentiation of DPSCs. Following identification of differentially expressed lncRNAs at different time points by reverse transcription‑quantitative polymerase chain reaction, profiling analysis was performed and a profile was further validated, in which lncRNA expression levels demonstrated significant upregulation. The next generation sequencing analysis identified 77 (58 upregulated and 19 downregulated) and 133 differentially expressed lncRNAs (73 upregulated and 60 downregulated) at 7 and 14 days post‑treatment, respectively. In addition, 34 lncRNAs were predicted to be strongly associated with 336 mRNA transcripts that underwent significant alterations during osteogenic differentiation. The present data demonstrated that one lncRNA, X inactive specific transcript, is essential for efficient osteogenic differentiation of DPSCs by alkaline phosphatase staining. In summary, the present findings provide insight for the understanding of how non‑coding RNAs are involved in regulating the osteogenic differentiation of DPSCs, which may further advance the translational studies of bone tissue engineering.