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Objective To explore the effect of lnc000727 on the differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into osteoblasts. Methods Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of lnc000727. The alkaline phosphatase (ALP) method was used to determine the differentiation of osteoblasts. The expression of lnc000727 in hBM-MSCs was over-expressed or inhibited by liposome transfection. The osteogenic differentiation markers Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and pontin were detected by RT-qPCR and Western blot. Pontin (OPN) mRNA and protein expression. The expression of key proteins in the Wnt/β-catenin pathway was analyzed. Results During the differentiation of hBM-MSCs osteoblasts, the expression of lnc000727 and ALP activity increased significantly(P＜0.05). Inhibition of lnc000727 could down-regulate ALP activity and inhibit the expression of osteogenic differentiation markers RUNX2, OCN, OPN and the expression of Wnt and β-catenin (P＜0.05); over-expression of lnc000727 could up-regulate ALP activity and promote the expressions of osteogenic differentiation markers RUNX2, OCN and OPN, and the expressions of Wnt and β-catenin (P＜0.05). Conclusions Lnc000727 promotes the differentiation of hBM-MSCs into osteoblasts, thereby inhibits the occurrence and development of osteoporosis.