miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury

Yuan Xiong; Faqi Cao; Liangcong Hu; Chenchen Yan; Lang Chen; Adriana C Panayi; Yun Sun; Wu Zhou; Peng Zhang; Qipeng Wu; Hang Xue; Mengfei Liu; Yi Liu; Jing Liu; Abudula Abududilibaier; Bobin Mi; Guohui Liu

doi:10.1016/j.omtn.2019.06.001

miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury

Mol Ther Nucleic Acids. 2019 Sep 6:17:223-234. doi: 10.1016/j.omtn.2019.06.001. Epub 2019 Jun 12.

Authors

Yuan Xiong¹, Faqi Cao¹, Liangcong Hu¹, Chenchen Yan¹, Lang Chen¹, Adriana C Panayi², Yun Sun³, Wu Zhou¹, Peng Zhang⁴, Qipeng Wu⁵, Hang Xue¹, Mengfei Liu¹, Yi Liu¹, Jing Liu¹, Abudula Abududilibaier¹, Bobin Mi⁶, Guohui Liu⁷

Affiliations

¹ Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
³ Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
⁴ Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China.
⁵ Department of Orthopaedics, Pu'ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁶ Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: mi19882@163.com.
⁷ Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: liuguohui@hust.edu.cn.

Abstract

Patients who sustain a traumatic brain injury (TBI) are known to have a significantly quicker fracture healing time than patients with isolated fractures, but the underlying mechanism has yet to be identified. In this study, we found that the upregulation of miRNA-26a-5p induced by TBI correlated with a decrease in phosphatase and tensin homolog (PTEN) in callus formation. In vitro, overexpressing miRNA-26a-5p inhibited PTEN expression and accelerated osteoblast differentiation, whereas silencing of miRNA-26a-5p inhibited osteoblast activity. Reduction of PTEN facilitated osteoblast differentiation via the PI3K/AKT signaling pathway. Through luciferase assays, we found evidence that PTEN is a miRNA-26a-5p target gene that negatively regulates the differentiation of osteoblasts. Moreover, the present study confirmed that preinjection of agomiR-26a-5p leads to increased bone formation. Collectively, these results indicate that miRNA-26a-5p overexpression may be a key factor governing the improved fracture healing observed in TBI patients after the downregulation of PTEN and PI3K/AKT signaling. Upregulation of miRNA-26a-5p may therefore be a promising therapeutic strategy for promoting fracture healing.

Keywords: PTEN; fracture; miRNA; traumatic brain injury.