MicroRNA-218 competes with differentiation media in the induction of osteogenic differentiation of mesenchymal stem cell
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ORIGINAL ARTICLE
MicroRNA‑218 competes with differentiation media in the induction of osteogenic differentiation of mesenchymal stem cell by regulating β‑catenin inhibitors Zohreh Karimi1 · Ehsan Seyedjafari2 · Arash Khojasteh3 · Seyed Mahmoud Hashemi4 · Bahram Kazemi5 · Samira Mohammadi‑Yeganeh1,5 Received: 28 January 2020 / Accepted: 30 September 2020 © Springer Nature B.V. 2020
Abstract Osteoporosis, a systemic skeletal disorder specified by low bone mass, is associated with bone fragility and the raised risk of fractures. Activation of the Wnt/β-catenin signaling pathway has been directly demonstrated as a prominent biological event in the prevention of osteoporosis. Recently, critical roles of microRNAs (miRNAs) were further revealed in Wnt/β-catenin signaling activation and thereby contributing to the development and maintenance of the human skeleton. In this study, we investigated whether miR-218 can significantly promote the osteogenic differentiation of mesenchymal stem cells in conditional media by regulating β-catenin signaling inhibitors. The pre-miRNA nucleotide sequence of miR-218 was cloned into the pEGP-miR vector. Next, human adipose tissue-derived mesenchymal stem cells (AD-MSCs) were isolated, characterized, and transfected using pEGP-miR-218.Subsequently, the osteogenic potential of AD-MSCs was investigated in different treated groups using alkaline phosphatase (ALP)activity, calcium mineral deposition, and the expression of osteogenesis-related genes. Finally, negative regulators of Wnt signaling targeted by miR-218 were bioinformatically predicted. Our results indicated a significant increase in the ALP activity, mineralization, and osteogenesis-related genes expression in the AD-MSCs transfected with pEGP-miR-218. Also, the bioinformatic surveys and gene expression results showed that adenomatosis polyposis coli (APC) and glycogen synthase kinase 3 (GSK3-β) were downregulated in the transfected AD-MSCs in both differential and conditional media. This study provided evidence that miR-218 can promote osteogenic differentiation of AD-MSCs even in conditional media. Therefore, our findings suggest miR-218 as a putative novel therapeutic candidate in the context of osteoporosis and other bone metabolism-related diseases. Keywords Osteogenesis · miR-218 · Mesenchymal stem cells · Wnt/β-catenin signaling pathway
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05885-7) contains supplementary material, which is available to authorized users. 1
Zohreh Karimi [email protected]
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Ehsan Seyedjafari [email protected]
Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
3
Seyed Mahmoud Hashemi [email protected]
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti Universi
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