miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury.
Xiong Yuan,Cao Faqi,Hu Liangcong,Yan Chenchen,Chen Lang,Panayi Adriana C,Sun Yun,Zhou Wu,Zhang Peng,Wu Qipeng,Xue Hang,Liu Mengfei,Liu Yi,Liu Jing,Abududilibaier Abudula,Mi Bobin,Liu Guohui
Molecular therapy. Nucleic acids
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.
The Association Between Traumatic Brain Injury and Accelerated Fracture Healing: A Study on the Effects of Growth Factors and Cytokines.
Mollahosseini Majid,Ahmadirad Hadis,Goujani Reza,Khorramdelazad Hossein
Journal of molecular neuroscience : MN
Evidence suggests that some systemic and local factors, including cytokines and growth factors in patients with traumatic brain injury (TBI), can play an essential role in accelerating fracture healing. The purpose of this study was to evaluate serum levels of some inflammatory cytokines and growth factors in patients with fracture and TBI as well as healthy subjects. In this study, a total number of 30 patients with a femoral fracture, 30 cases with TBI, 30 patients with TBI and a femoral fracture (fracture + TBI group), and 30 healthy subjects were recruited. The Glasgow Coma Scale (GCS) scores were also determined upon their admission. Then, the serum levels of fibroblast growth factor 2 (FGF-2), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), bone morphogenetic protein 2 (BMP-2), insulin-like growth factor 1 (IGF-1), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA) technique, 12 h and 4 weeks after injury and hospital admission. The study results demonstrated that the serum levels of BMP-2, FGF-2, IL-1β, and PDGF in the femoral fracture + TBI group increased significantly over 12 h and after 4 weeks compared with other groups, but the serum levels of IGF-I, IL-6, and TGF-β in this group increased in a significant manner at 12 h compared with other studied groups. The findings also showed that the time to union of a femoral fracture was shorter in the fracture + TBI group than in cases with a femoral fracture alone (p = 0.03). Accordingly, it seems that elevated serum levels of BMP-2, PDGF, FGF-2, and IL-1β may be associated with healing acceleration in fracture + TBI patients. However, further studies are needed to confirm this claim.