Beneficial role of microRNA‑328‑3p in fracture healing by enhancing osteoblastic viability through the PTEN/PI3K/AKT pathway

Abstract

Although fragility fracture is a global public health burden, the mechanisms underlying fracture healing remain unclear. The present study aimed to assess the dynamic expression pattern of microRNA-328-3p (miR-328-3p) during fracture healing in patients with fragility fracture and to explore the functional role and mechanisms of miR-328-3p in the regulation of osteoblastic viability. The expression levels of miR-328-3p was examined using reverse transcription-quantitative PCR (RT-qPCR). Osteoblastic proliferation and apoptosis were analyzed via MTT and flow cytometry assays. A luciferase reporter assay was adopted to confirm the interaction between miR-328-3p and its target gene PTEN, and western blotting was used to explore the activity of PI3K/AKT signaling. The results of the present study demonstrated that serum miR-328-3p expression did not significantly differ at the early stage of healing in patients with fracture, but was markedly decreased 14 and 21 days post fixation (P<0.01). PTEN was demonstrated to be a target gene of miR-328-3p and was inhibited by miR-328-3p overexpression in osteoblasts (P<0.001). miR-328-3p overexpression increased osteoblastic proliferation but decreased apoptotic rate, with these effects being reversed by PTEN overexpression (P<0.05). The expression of phosphorylated-AKT was elevated in osteoblasts by miR-328-3p overexpression, but this effect was abolished by overexpressing PTEN. Thus, the present study revealed that miR-328-3p may accelerate fracture healing by promoting osteoblastic viability through the PTEN/PI3K/AKT pathway.

Signature of circulating small non-coding RNAs during early fracture healing in mice

“…Also, in another study with osteoporotic fractures, miR-328-3p was reduced in circulation of postmenopausal women, and repression of miR-328-3p reduced significantly alkaline phosphatase activity during osteogenic differentiation of human adipose-derived stem cells but did not affect calcium deposition ( Weilner et al, 2015 ). In humans with fragility fractures, miR-328-3p decreased in serum at 14 and 21 days postfixation ( W. Xie et al, 2020 ). Further, miR-328-3p targets PTEN and its overexpression decreases PTEN/P13K/AKT, increases osteoblast differentiation and decreases apoptotic rate of human osteoblast cells, suggesting that miR-328-3p accelerates fracture healing by promoting osteoblast viability.…”

Hu’po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway

“…The injury and healing of fracture are related to the activation of the PI3K/AKT signal pathway. Activating PI3K/AKT pathway can not only promote the osteogenic differentiation of bone marrow stem cells ( Zhao et al, 2020 ) but also enhance the viability of osteoblasts ( Xie et al, 2020 ). In addition, the activation of the PI3K/AKT pathway is one of the mechanisms that the fracture healing rate of TBI patients is faster than that of single fracture patients ( Hu et al, 2021 ).…”

The comprehensive detection of miRNA and circRNA in the regulation of intramuscular and subcutaneous adipose tissue of Laiwu pig

“…MiR-328 can reduce inflammation, apoptosis, and oxidative stress of endothelial cells induced by oxidized low-density lipoprotein (Ox-LDL) by specifically binding to HMGB1 59 . Overexpression of miR-328 can inhibit the expression of PTEN and inhibit the activation of PI3K-Akt signaling pathway 60 . The activity of PI3K-Akt signal pathway was decreased, and glucose absorption was decreased, thereby regulating lipid metabolism.…”