Parathyroid Hormone-regulation of Runx2 by MiR-290 for Matrix Metalloproteinase-13 Expression in Rat Osteoblastic Cells

Abstract

Background: The dynamic changes that bone undergoes during the ensemble of remodeling are administered by vital factors like Runx2 (a bone transcription factor) and matrix metalloproteinases (MMPs).

Aims: Parathyroid hormone (PTH), an FDA approved drug for bone-related ailments, was seen to stimulate MMP-13 expression via Runx2 to ultimately aid in the bone remodeling process. MicroRNAs (miRNAs) have been shown to play a major role in controlling bone metabolism, and the use of miRNAs has recently become promising therapeutic avenues for the treatment of many diseases, including bone disorders. Thus, in this study, we attempted to investigate and evaluate the expression of MMP-13 via a miRNA profile targeting Runx2 under PTH-regulation in rat osteoblastic cells.

Methods: PTH stimulated the expression of MMP-13 mRNA significantly at 4 h in rat osteoblastic cells (UMR106-01). Runx2 was required for PTH-stimulation of MMP-13 expression, in silico scrutiny generated 14 unique miRNAs targeting Runx2, and among these miRNAs, miR-290 was significantly downregulated by PTH-treatment in UMR106- 01 cells and in rat primary osteoblasts.

Results: Overexpression of miR-290 decreased the expression of Runx2, the binding of Runx2 at the MMP-13 promoter, and the expression of MMP-13 mRNA in PTH-treated UMR106-01 cells. A dual luciferase reporter assay identified the direct targeting of Runx2 mRNA by miR-290 in these cells.

Conclusion: Our findings indicate that the PTH-responsive miR-290 regulated Runx2- mediated MMP-13 expression in rat osteoblastic cells, suggesting miR-290 as a molecular marker or target in bone and bone-related diseases.

Keywords: Bone remodeling; Matrix metalloproteinase-13; Osteoblasts; Parathyroid hormone; Runx2; miR-290.