Parathyroid hormone-induced down-regulation of miR-532-5p for matrix metalloproteinase-13 expression in rat osteoblasts.

Abstract

Parathyroid hormone (PTH) acts on osteoblasts and functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We previously reported that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13) in rat osteoblasts and that MMP-13 plays a key role in bone remodeling, endochondral bone formation, and bone repair. Recent evidence indicated that microRNAs (miRNAs) have regulatory functions in bone metabolism. In this study, we hypothesized that the down-regulation of miRNAs that target MMP-13 by PTH leads to the stimulation of MMP-13 expression in osteoblasts. We used various bioinformatic tools to identify miRNAs that putatively target rat MMP-13. Among these miRNAs, the expression of miR-532-5p in rat osteoblasts decreased at 4 h of PTH-treatment, whereas MMP-13 mRNA expression was maximal at the same time point. When an miR-532-5p mimic was transiently transfected into UMR-106-01 cells, MMP-13 mRNA and protein expression decreased. Using a luciferase reporter assay system, we also identified that miR-532-5p directly targeted the 3' UTRs of MMP-13 gene. Based on these results, we suggest that PTH-induced down-regulation of miR-532-5p resulted in the stimulation of MMP-13 expression in rat osteoblasts. This study identified a significant role of miRNA in controlling bone remodeling via PTH-stimulated MMP-13 expression. This finding enhances our understanding of bone metabolism and bone-related diseases and it could provide information regarding the usage of miRNAs as therapeutic agents or biomarkers.