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

Vishal Mohanakrishnan, Arumugam Balasubramanian, Gokulnath Mahalingam, Nicola Partridge, Ilangovan Ramachandran, Nagarajan Selvamurugan

Research output: Contribution to journalArticle

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 4h 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.

Original languageEnglish (US)
JournalJournal of Cellular Biochemistry
DOIs
StateAccepted/In press - Jan 1 2018

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Matrix Metalloproteinase 13
Osteoblasts
Parathyroid Hormone
Rats
Down-Regulation
MicroRNAs
Bone
Bone Remodeling
Bone and Bones
Metabolism
Messenger RNA
Bone Diseases
3' Untranslated Regions
Computational Biology
Luciferases
Osteogenesis
Biomarkers
Bioinformatics
Homeostasis
Assays

Keywords

  • MiR-532-5p
  • MMP-13
  • Osteoblasts
  • PTH

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Parathyroid hormone-induced down-regulation of miR-532-5p for matrix metalloproteinase-13 expression in rat osteoblasts. / Mohanakrishnan, Vishal; Balasubramanian, Arumugam; Mahalingam, Gokulnath; Partridge, Nicola; Ramachandran, Ilangovan; Selvamurugan, Nagarajan.

In: Journal of Cellular Biochemistry, 01.01.2018.

Research output: Contribution to journalArticle

Mohanakrishnan, Vishal ; Balasubramanian, Arumugam ; Mahalingam, Gokulnath ; Partridge, Nicola ; Ramachandran, Ilangovan ; Selvamurugan, Nagarajan. / Parathyroid hormone-induced down-regulation of miR-532-5p for matrix metalloproteinase-13 expression in rat osteoblasts. In: Journal of Cellular Biochemistry. 2018.
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