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MicroRNA-595 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by targeting HMGA2


Bingjun Gao
Yarong Wu
Lijian Zhou
Xin Chen

Abstract

Purpose: To investigate the effect of miR-595 on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
Methods: Human BMSCs were osteogenically differentiated, and protein expression of alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2) were evaluated by western blot. Expression of miR-595 was measured by quantitative reverse transcription (qRT-PCR). The effect of miR-595 on viability of BMSCs was determined by MTT assay. Osteogenic differentiation of BMSCs was assessed by ALP and Alizarin red S (ARS) staining. The target gene of miR-595 was predicted by TargetScan analysis and validated by luciferase activity assay.
Results: MiR-595 expression was higher in osteogenically differentiated BMSCs than in undifferentiated BMSCs (p < 0.01). Osteogenic ALP, OCN, and RUNX2 were also upregulated (p < 0.01). MiR-595 expression increased the viability of BMSCs, mineralized bone matrix formation, and ALP activity. High mobility group AT-hook 2 (HMGA2) expression was lower in osteogenically differentiated BMSCs and was found to be a target of miR-595. Overexpression of HMGA2 attenuated the miR-595-induced increase in cell viability, ALP activity, mineralized bone matrix formation, and osteogenic gene expression in BMSCs.
Conclusion: The miR-595/HMGA2 axis is involved in osteogenic differentiation of BMSCs suggesting that it is a promising therapeutic target for osteoporosis.


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eISSN: 1596-9827
print ISSN: 1596-5996