Long non-coding RNA HULC promotes proliferation and osteogenic differentiation of bone mesenchymal stem cells via down-regulation of miR-195

X.-R. Jiang, N. Guo, X.-Q. Li, H.-Y. Yang, K. Wang, C.-L. Zhang, G.-S. Li, G.-D. Li

Department of Orthopedics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. guodonglin0034@sohu.com

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• Orthopedics

OBJECTIVE: LncRNAs HULC has been reported to be important regulators in the development of various human diseases. However, the role of HULC in bone mesenchymal stem cells (BMSCs) remains unclear. The present study aimed to explore the regulatory effect of HULC on proliferation and osteogenic differentiation of BMSCs and the underlying mechanism.

MATERIALS AND METHODS: The expression of HULC and miR-195 in BMSCs were altered by transfection and measured by qRT-PCR. Cell viability was measured by the CCK-8 assay. Osteogenic differentiation of BMSCs was determined by evaluation of osteogenic markers (Ocn, ALP, Runx2, and Col-1) expression levels using Western blot and qRT-PCR. Furthermore, Western blot was performed to assess the expression of proliferation-related factors, Wnt/β-catenin and p38MAPK pathway-related factors.

RESULTS: HULC overexpression significantly increased cell viability, down-regulated p21 expression but up-regulated CyclinD1 expression, and promoted the levels of osteogenic markers. However, the complete opposite effect was observed in HULC knockdown. Notably, miR-195 expression was negatively regulated by HULC and miR-195 exerted a reversed effect of HULC on BMSCs. Moreover, miR-195 mediated the regulatory effect of HULC on BMSCs proliferation and osteogenic differentiation, as miR-195 mimic abolished the effect of HULC overexpression on BMSCs. We also found that HULC overexpression enhanced the activation of Wnt/β-catenin and p38MAPK pathway through down-regulating miR-195.

CONCLUSIONS: We revealed that HULC promoted proliferation and osteogenic differentiation of BMSCs. The potential mechanism might be involved in its negative regulation on miR-195 and enhanced activation of Wnt/β-catenin and p38MAPK pathway.

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