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Am J Transl Res. 2019 Aug 15;11(8):4746-4760. eCollection 2019.

Downregulation of microRNA-16-5p accelerates fracture healing by promoting proliferation and inhibiting apoptosis of osteoblasts in patients with traumatic brain injury.

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Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, China.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, China.


Patients who suffered a traumatic brain injury (TBI) show a faster fracture healing than patients with isolated fractures. Prior studies have suggested that this process may be accelerated through the inhibition of key microRNAs. In this study, we aimed to explore the mechanisms underlying this phenomenon, with a special focus on miR-16-5p, which is markedly decreased in patients with TBI. In vitro, miR-16-5p over-expression significantly inhibited cell proliferation in MC3T3-E1 cells transfected with agomiR-16-5p. Flow cytometry analysis further demonstrated that the overexpression of miR-16-5p induced cell cycle G1/S phase arrest and apoptosis. Moreover, target prediction and luciferase reporter assay demonstrated that miR-16-5p could negatively regulate Bcl-2 and Cyclin-D1 expression. Meanwhile, Bcl-2 and Cyclin-D1 were up-regulated after osteogenic differentiation while the down-regulation of endogenous Bcl-2 and Cyclin-D suppressed the osteogenic differentiation of MC3T3-E1 cells. In vivo, PBS, agomiR-16-5p and antagomiR-16-5p were injected into fracture sites to assess any improvements in fracture healing, which further confirmed the negative effect of miR-16-5p on fracture healing. Together, these results demonstrate miR-16-5p downregulation may accelerate fracture healing by enhancing the proliferation and inhibiting the apoptosis of osteoblasts in patients with both fractures and TBI. These phenomena may be exploited in the treatment of fractures.


Traumatic brain injury; fracture; miRNA


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