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MicroRNA-218 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells and Accelerates Bone Fracture Healing

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Abstract

As a regulator of osteogenesis, microRNA-218 (miR-218) is reported to promote osteogenesis of mesenchymal stem cells (MSCs). However, the in vivo osteogenic effect of miR-218 remains elusive. In this study, miR-218 was confirmed to promote osteogenic differentiation of MSCs by stimulating the alkaline phosphatase activity, calcium nodule formation, and osteogenic marker gene expression. For in vivo study, the miR-218-overexpressing BMSCs were locally administrated into the fracture sites in a femur fracture mouse model. Based on the X-rays, micro-computed tomography, mechanical testing, histology, and immunohistochemistry examinations, miR-218 overexpression improved new bone formation and accelerated fracture healing. These findings suggest that miR-218 may be a promising therapeutic target for bone repair in future clinical applications.

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Acknowledgements

The work was partially supported by grants from Research Grants Council of the Hong Kong SAR, China (Project No. 14119115, 14160917, N_CityU102/15, T13-402/17-N); National Natural Science Foundation of China (81772404, 81430049, and 81772322); Hong Kong Innovation Technology Commission Funds (ITS/UIM-305). This study was also supported in part by SMART program, Lui Che Woo Institute of Innovative Medicine.

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Author notes

  1. Liu Shi and Lu Feng have equal contribution to this article.

Authors and Affiliations

  1. Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China

    Liu Shi, Lu Feng, Yang Liu, Wei-ping Lin & Gang Li

  2. Department of Orthopaedics, Zibo Central Hospital, 54 West Gongqingtuan Road, Zibo, Shandong, People’s Republic of China

    Ji-qiang Duan

  3. Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China

    Jin-fang Zhang

  4. The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of China

    Gang Li

  5. Li Ka Shing Institute of Health Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong SAR, People’s Republic of China

    Gang Li

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  1. Liu Shi
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Contributions

JZ and GL designed and supervised all the experiments; LS, LF, and YL conducted experiments, analyzed the data, and prepared the manuscript. JD and WL analyzed the IHC staining blindly. All authors reviewed and approved the manuscript.

Corresponding authors

Correspondence to Jin-fang Zhang or Gang Li.

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Conflict of interest

Liu Shi, Lu Feng, Yang Liu, Ji-qiang Duan, Wei-ping Lin, Jin-fang Zhang, and Gang Li declare that none of them have any conflict of interest.

Human and Animal Rights and Informed Consent

The animal experiemts were carried out with full ethical approval of The Chinese University of Hong Kong animal ethical committee  accorign to the laws and regulations for animal experiemts of Hong Kong.

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Shi, L., Feng, L., Liu, Y. et al. MicroRNA-218 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells and Accelerates Bone Fracture Healing. Calcif Tissue Int 103, 227–236 (2018). https://doi.org/10.1007/s00223-018-0410-8

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  • DOI: https://doi.org/10.1007/s00223-018-0410-8

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