MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1

J Cell Mol Med. 2019 Sep;23(9):6140-6153. doi: 10.1111/jcmm.14490. Epub 2019 Jul 14.

Abstract

Osteoporosis is closely associated with the dysfunction of bone metabolism, which is caused by the imbalance between new bone formation and bone resorption. Osteogenic differentiation plays a vital role in maintaining the balance of bone microenvironment. The present study investigated whether melatonin participated in the osteogenic commitment of bone marrow mesenchymal stem cells (BMSCs) and further explored its underlying mechanisms. Our data showed that melatonin exhibited the capacity of regulating osteogenic differentiation of BMSCs, which was blocked by its membrane receptor inhibitor luzindole. Further study demonstrated that the expression of miR-92b-5p was up-regulated in BMSCs after administration of melatonin, and transfection of miR-92b-5p accelerated osteogenesis of BMSCs. In contrast, silence of miR-92b-5p inhibited the osteogenesis of BMSCs. The increase in osteoblast differentiation of BMSCs caused by melatonin was attenuated by miR-92b-5p AMO as well. Luciferase reporter assay, real-time qPCR analysis and western blot analysis confirmed that miR-92b-5p was involved in osteogenesis by directly targeting intracellular adhesion molecule-1 (ICAM-1). Melatonin improved the expression of miR-92b-5p, which could regulate the differentiation of BMSCs into osteoblasts by targeting ICAM-1. This study provided novel methods for treating osteoporosis.

Keywords: BMSCs; ICAM-1; MiRNA; melatonin; osteogenic differentiation; osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Resorption / genetics
  • Bone Resorption / pathology
  • Bone Resorption / therapy
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Melatonin / genetics*
  • Melatonin / pharmacology
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • Osteoblasts / drug effects
  • Osteogenesis / drug effects
  • Osteogenesis / genetics*
  • Osteoporosis / genetics
  • Osteoporosis / pathology
  • Osteoporosis / therapy
  • Tryptamines / pharmacology

Substances

  • ICAM1 protein, human
  • MIRN92 microRNA, human
  • MicroRNAs
  • Tryptamines
  • luzindole
  • Intercellular Adhesion Molecule-1
  • Melatonin