MicroRNA-148a inhibition protects against ovariectomy-induced osteoporosis through PI3K/AKT signaling by estrogen receptor α

Abstract

The present study aimed to investigate the effect of microRNA-148a downregulation on osteoporosis by using an ovariectomized rat model. Reverse transcription-quantitative polymerase chain reaction was used to analyze microRNA-148a expression levels, MTT and flow cytometry assays were used to examine cytotoxicity and apoptosis, respectively. The gap-associatedproteins were quantified using western blotting. The expression of microRNA-148a was significantly increased in osteoporosis rat following ovariectomy. Overexpression of microRNA-148a significantly promoted apoptosis and inhibited cell growth, whereas downregulation of microRNA-148a significantly reduced apoptosis and increased cell growth. Overexpression of microRNA-148a significantly reduced estrogen receptor a (ERα) protein expression and suppressed phosphoinositide-3-kinase regulatory subunit 1 (PI3K) and phosphorylated-protein kinase B (AKT) protein expression in osteoblasts in vitro. The inhibition of ERα increased the microRNA-148a effect on apoptosis in osteoblasts in vitro. Subsequently, LY294002, an PI3K inhibitor, significantly increased the effect of microRNA-148a on apoptosis in osteoblasts in vitro. The findings of the present study revealed that anti-microRNA-148a protected cells against ovariectomy-induced osteoporosis through ERα by PI3K/AKT signaling.