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

Abstract Patients suffering from traumatic brain injuries (TBIs) 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 correlates with a decrease of phosphatases and tensin homolog (PTEN) in callus formation. In vitro, over-expressing miRNA-26a-5p inhibits PTEN expression and accelerates osteoblast differentiation, whereas silencing of miRNA-26a-5p inhibits osteoblast activity. Reduction of PTEN facilitates osteoblast differentiation via the PI3K/AKT signaling pathway. Through luciferase assays, we found evidence that PTEN is a miRNA-26a-5p target gene negatively regulating the differentiation of osteoblasts. Moreover, the present study also confirmed that pre-injection 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 via down-regulation of PTEN and PI3K/AKT signaling. Upregulation of miRNA-26a-5p may therefore be a promising therapeutic strategy to promote fracture healing.