Protein‑coding genes and small non‑coding microRNAs involved in the guidance of differentiation in mesenchymal stem cells (MSCs) into osteoblasts have been extensively investigated in previous studies. However, long non‑coding RNAs (lncRNAs), which account for a large proportion of the genomic sequences in numerous species, have not yet been reported. In the present study, the lncRNA expression profile was analyzed using the Arraystar lncRNA array in C3H10T1/2 MSCs undergoing early osteoblast differentiation and 116 differentially expressed lncRNAs were identified between BMP‑2 treated and untreated groups. Among these lncRNAs, 59 were upregulated and 57 were downregulated in BMP‑2 treated groups. In addition, 24 cooperatively differentially expressed lncRNAs and nearby mRNA pairs were found. For example, mouselincRNA0231 and its nearby gene, EGFR, were downregulated, while lncRNA NR_027652 and its nearby gene, DLK1, were upregulated. These observations may be part of the regulatory mechanisms of lncRNAs in the control of osteoblast differentiaton. In conclusion, results of the present study indicate that lncRNA expression profiles are significantly altered in C3H10T1/2 undergoing early osteoblast differentiation and these results may provide insight into the mechanisms responsible for osteoblast differentiation.