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

Molecular Therapy: Nucleic Acids (Sep 2019)

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

Affiliations

Yuan Xiong: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Faqi Cao: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Liangcong Hu: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Chenchen Yan: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Lang Chen: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Adriana C. Panayi: Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215, USA
Yun Sun: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Wu Zhou: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Peng Zhang: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China
Qipeng Wu: Department of Orthopaedics, Pu’ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Hang Xue: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Mengfei Liu: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Yi Liu: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Jing Liu: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Abudula Abududilibaier: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Bobin Mi: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Corresponding author: Bobin Mi, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Guohui Liu: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Corresponding author: Guohui Liu, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Journal volume & issue: Vol. 17
pp. 223 – 234

Abstract

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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: traumatic brain injury, fracture, miRNA, PTEN

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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