MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

摘要

Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 ( FOXO1 ), growth differentiation factor 5 ( GDF5 ) and SRY-box 6 ( SOX6 ) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1 , GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1 , GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1 , GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1 , GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1 , GDF5 and SOX6 .