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- Title
Inhibition of microRNA-221-5p induces osteogenic differentiation by directly targeting smad3 in myeloma bone disease mesenchymal stem cells.
- Authors
Fan, Fang-Yi; Deng, Rui; Lai, Si-Han; Wen, Qin; Zeng, Yunjing; Gao, Lei; Liu, Yao; Kong, Peiyan; Zhong, Jiangfan; Su, Yi; Zhang, Xi
- 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.
- Subjects
MESENCHYMAL stem cells; BONE diseases; BONE marrow; ONCOLOGY; MULTIPLE myeloma
- Publication
Oncology Letters, 2019, Vol 18, Issue 6, p6536
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2019.10992