miR-141 Improve Osteoporosis by Promoting Osteoblast Differentiation through Targeting RICTOR

Abstract

We investigated the regulatory roles of miR-141 and RICTOR genes in osteoporosis (OP) and explored the potential therapeutic value of miR-141 in OP by targeting RICTOR gene. The role of miR-141 and RICTOR genes as regulators in ovariectomized (OVX) rats was determined using RT-qPCR assays in osteoporosis models of OVX rats. and their expression levels in OVX rats and related clinical features were further analyzed. The functional role of miR-141/RICTOR pathway was investigated using plasmids. miR-141 was lowly expressed in OVX rats, while RICTOR gene was highly expressed. Bioconductivity prediction analysis revealed potential regulatory sites for miR-141 and RICTOR. Promotion of miR-141 or inhibition of RICTOR expression levels using miR-141 mimic/ si-RNA RICTOR in OVX rats reduced ALP activity as well as expression levels of nuclear factor-kappa B ligand (RANKL), bone gla protein (BGP) and tartrate resistant acid phosphatase (TRAP), while promoting osteoprotegerin production. Healthy rats with elevated RICTOR expression levels showed same symptoms of OVX, whereas miR-141 mimic injection improved the OP symptoms in rats. Our data suggest that miR-141 regulate ALP activity as well as osteoprotegerin, RANKL, BGP and TRAP levels by targeting RICTOR gene, impacting the development of OP.