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

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.

Citation

Liang Sun, Zhong Li, Hanzhong Xue, Teng Ma, Cheng Ren, Ming Li, Yao Lu, He Sun, Kun Zhang. MiR-26a promotes fracture healing of nonunion rats possibly by targeting SOSTDC1 and further activating Wnt/β-catenin signaling pathway. Molecular and cellular biochemistry. 2019 Oct;460(1-2):165-173

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PMID: 31313025

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