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MiR-26a promotes fracture healing of nonunion rats possibly by targeting SOSTDC1 and further activating Wnt/β-catenin signaling pathway

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Abstract

Nonunion is a serious complication after fracture due to its difficulty of self-healing. MicroRNA-26a (miR-26a) has been known to play a crucial role in bone metabolism. In this study, we established a rat nonunion model by removing periosteum, and found that miR-26a was significantly upregulated. Osteogenic differentiation of mesenchymal stem cells (MSCs) isolated from bone marrow transfected with miR-26a mimics was significantly enhanced, evidenced by increased calcium deposition and expression levels of alkaline phosphatase (ALP) and osteocalcin. Bioinformatics analysis suggested that sclerostin domain-containing 1 (SOSTDC1) may be a target of miR-26a, which was confirmed by dual-luciferase assay and western blot. Besides, miR-26a was used for nonunion rats. Delightfully, radiographs of nonunion rats with miR-26a mimics administration showed obvious new bone formation compared with nonhealing control. Hematoxylin–eosin and Masson staining assays revealed that osteogenesis capacity was greatly enhanced by miR-26a mimics’ administration. In addition, miR-26a mimics could promote osteogenic differentiation in nonunion rats, evidenced by increased protein levels of ALP and osteocalcin, while SOSTDC1 was suppressed. The injection of miR-26a mimics also gave rise to phosphorylation of GSK3β and nuclear accumulation of β-catenin, which indicated the activation of canonical Wnt/β-catenin signaling. In conclusion, we demonstrated that miR-26a promoted fracture healing of rats with nonunion in vivo and osteogenic differentiation of MSCs in vitro, possibly by targeting SOSTDC1, and that Wnt/β-catenin signaling pathway was involved in this process.

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Acknowledgements

This study was supported by grants from the Projects of Department of Science and Technology, Shaanxi Province (Nos. 2012JM4046 and 2013K14-02-12).

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Authors and Affiliations

  1. Department of Traumatic Orthopedics, Honghui Hospital, Xi’an Jiaotong University, 555 West Youyi Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Liang Sun, Zhong Li, Hanzhong Xue, Teng Ma, Cheng Ren, Ming Li, Yao Lu & Kun Zhang

  2. Department of Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi, People’s Republic of China

    He Sun

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  1. Liang Sun
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Sun, L., Li, Z., Xue, H. et al. MiR-26a promotes fracture healing of nonunion rats possibly by targeting SOSTDC1 and further activating Wnt/β-catenin signaling pathway. Mol Cell Biochem 460, 165–173 (2019). https://doi.org/10.1007/s11010-019-03578-9

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