miR-149-3p Regulates the Switch between Adipogenic and Osteogenic Differentiation of BMSCs by Targeting FTO

Yuan Li; Fan Yang; Manqi Gao; Rui Gong; Mengyu Jin; Tianyi Liu; Yi Sun; Yutuo Fu; Qi Huang; Wenwen Zhang; Shenzhen Liu; Meixi Yu; Gege Yan; Chao Feng; Mingyu He; Lai Zhang; Fengzhi Ding; Wenya Ma; Zhenggang Bi; Chaoqian Xu; Ye Yuan; Benzhi Cai; Lei Yang

Molecular Therapy: Nucleic Acids (Sep 2019)

miR-149-3p Regulates the Switch between Adipogenic and Osteogenic Differentiation of BMSCs by Targeting FTO

Yuan Li,
Fan Yang,
Manqi Gao,
Rui Gong,
Mengyu Jin,
Tianyi Liu,
Yi Sun,
Yutuo Fu,
Qi Huang,
Wenwen Zhang,
Shenzhen Liu,
Meixi Yu,
Gege Yan,
Chao Feng,
Mingyu He,
Lai Zhang,
Fengzhi Ding,
Wenya Ma,
Zhenggang Bi,
Chaoqian Xu,
Ye Yuan,
Benzhi Cai,
Lei Yang

Affiliations

Yuan Li: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Fan Yang: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Manqi Gao: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Rui Gong: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Mengyu Jin: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Tianyi Liu: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China; College of Pharmacy, University of Cincinnati, Cincinnati, OH 45220, USA
Yi Sun: Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Yutuo Fu: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China
Qi Huang: Department of Pharmacology, Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China
Wenwen Zhang: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Shenzhen Liu: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Meixi Yu: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Gege Yan: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Chao Feng: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Mingyu He: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Lai Zhang: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Fengzhi Ding: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Wenya Ma: Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China
Zhenggang Bi: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China
Chaoqian Xu: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Ye Yuan: Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China
Benzhi Cai: Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China; Corresponding author: Benzhi Cai, Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China.
Lei Yang: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China; Corresponding author: Lei Yang, Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China.

Journal volume & issue: Vol. 17
pp. 590 – 600

Abstract

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Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulating the differentiation of BMSCs into particular lineage. However, the role of miR-149-3p in the adipogenic and osteogenic differentiation of BMSCs has not been extensively discovered. In this study, we aimed to detect the expression levels of miR-149-3p during the differentiation of BMSCs and investigate whether miR-149-3p participated in the lineage choice of BMSCs or not. Compared with mimic-negative control (NC), miR-149-3p mimic decreased the adipogenic differentiation potential of BMSCs and increased the osteogenic differentiation potential. Further analysis revealed that overexpression of miR-149-3p repressed the expression of fat mass and obesity-associated (FTO) gene through binding to the 3ʹ UTR of the FTO mRNA. Also, the role of miR-149-3p mimic in inhibiting adipogenic lineage differentiation and potentiating osteogenic lineage differentiation was mainly through targeting FTO, which also played an important role in regulating body weight and fat mass. In addition, BMSCs treated with miR-149-3p anti-miRNA oligonucleotide (AMO) exhibited higher potential to differentiate into adipocytes and lower tendency to differentiate into osteoblasts compared with BMSCs transfected with NC. In summary, our results detected the effects of miR-149-3p in cell fate specification of BMSCs and revealed that miR-149-3p inhibited the adipogenic differentiation of BMSCs via a miR-149-3p/FTO regulatory axis. This study provided cellular and molecular insights into the observation that miR-149-3p was a prospective candidate gene for BMSC-based bone tissue engineering in treating osteoporosis. Keywords: miRNA, osteoporosis, osteogenesis, adipogenesis, BMSC, differentiation, FTO

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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