Inhibition of microRNA‑221‑5p induces osteogenic differentiation by directly targeting smad3 in myeloma bone disease mesenchymal stem cells

Fan,Fang‑Yi; Deng,Rui; Lai,Si‑Han; Wen,Qin; Zeng,Yunjing; Gao,Lei; Liu,Yao; Kong,Peiyan; Zhong,Jiangfan; Su,Yi; Zhang,Xi

doi:10.3892/ol.2019.10992

Inhibition of microRNA‑221‑5p induces osteogenic differentiation by directly targeting smad3 in myeloma bone disease mesenchymal stem cells

Authors:
- Fang‑Yi Fan
- Rui Deng
- Si‑Han Lai
- Qin Wen
- Yunjing Zeng
- Lei Gao
- Yao Liu
- Peiyan Kong
- Jiangfan Zhong
- Yi Su
- Xi Zhang
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Affiliations: Department of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, Sichuan 400037, P.R. China, Department of Hematology and Hematopoetic Stem Cell Transplantation Centre, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China
Published online on: October 17, 2019 https://doi.org/10.3892/ol.2019.10992
Pages: 6536-6544
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myeloma bone disease (MBD) is one of the clinical features of multiple myeloma, which contributes to the attenuation of osteoblast function. Bone marrow mesenchymal stem cells exhibit a high potential for differentiation into osteoblasts. A number of studies have reported that microRNAs (miRs) serve a vital role in mesenchymal stem cell (MSC) osteogenesis; however, the role of miR‑221‑5p in the osteogenic differentiation of MBD‑MSCs remains unclear. The present study revealed that the osteogenic differentiation capacity of MBD‑MSCs was reduced compared with that of normal (N)‑MSCs. Further experiments demonstrated that miR‑221‑5p expression was downregulated in N‑MSCs following osteoblast induction while no obvious alterations in expression levels were observed in MBD‑MSCs. The inhibition of miR‑221‑5p promoted the osteogenic differentiation of MBD‑MSCs. Bioinformatics, luciferase reporter assays, reverse transcription‑quantitative PCR and western blotting assays indicated that smad family member 3 (smad3) was a direct target of miR‑221‑5p in MBD‑MSCs. A negative association was identified between the expression levels of smad3 and miR‑221‑5p. Investigations of the molecular mechanism indicated that suppressed miR‑221‑5p could regulate the osteogenic differentiation of MBD‑MSCs by upregulating smad3 expression. It was also identified that the PI3K/AKT/mTOR signaling pathway was activated following miR‑221‑5p inhibition, and this increased the osteogenic differentiation capacity of MBD‑MSCs. The present study may improve the understanding regarding the role of miR‑221‑5p in the regulation of osteogenic differentiation, and may contribute to the development of a novel therapy for MBD.

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