MiR-491-3p is down-regulated in postmenopausal osteoporosis and affects growth, differentiation and apoptosis of hFOB1.19 cells through targeting CTSS

Folia Histochem Cytobiol. 2020;58(1):9-16. doi: 10.5603/FHC.a2020.0001. Epub 2020 Mar 16.

Abstract

Background: Postmenopausal osteoporosis (PMO) is a common disease related to aging, which has been paid increasing attention in recent years because of its serious complications. MiR-491-3p was found to play a crucial roles in several diseases. However, the role of miR-491-3p in PMO has yet not been studied. Our research intends to explore the impact of miR-491-3p on PMO in the in vitro model.

Material and methods: The expression patterns of miR-491-3p and cathepsin S (CTSS) in patients with PMO were acquired from the GEO database. The human osteoblast cell hFOB1.19 was used to detect the function of miR-491-3p and CTSS in PMO. The viability and apoptosis of hFOB1.19 cells were measured by cell counting kit 8 and flow cytometry assays. The apoptosis and differentiation related proteins were analyzed by western blotting. The relationship between miR-491-3p and CTSS was predicted by appropriate software and affirmed by luciferase assay.

Results: MiR-491-3p expression was lower in patients with PMO. The up-regulation of miR-491-3p in hFOB1.19 cells increased their viability and differentiation and inhibited their apoptosis. CTSS, which was highly expressed in patients with PMO, was confirmed as a direct target of miR-491-3p and was found to be inversely modulated by miR-491-3p. The rescue assays showed that overexpression of CTSS suppressed the promoting effects of miR-491-3p mimic on the proliferation and differentiation of hFOB1.19 cells, and repressed the inhibitory effects of miR-491-3p mimic on apoptosis of hFOB1.19 cells.

Conclusions: The results of our study showed that miR-491-3p could ameliorate biological characteristics of hFOB1.19 cells by reducing CTSS expression suggesting that miR-491-3p/CTSS might be a potential biomarker for the diagnosis and treatment of PMO.

Keywords: apoptosis; cathepsin S; flow cytometry; miR-491-3p; osteoblastic hFOB1.19 cells; postmenopausal osteoporosis; proliferation.

MeSH terms

  • Apoptosis / physiology*
  • Biomarkers / metabolism
  • Cathepsins / metabolism*
  • Cell Differentiation / physiology*
  • Cell Line
  • Cell Proliferation / physiology*
  • Down-Regulation
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Osteoporosis, Postmenopausal / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • MIRN491 microRNA, human
  • MicroRNAs
  • Cathepsins
  • cathepsin S