Icariin triggers osteogenic differentiation of bone marrow stem cells by up-regulating miR-335-5p

Exp Cell Res. 2022 May 15;414(2):113085. doi: 10.1016/j.yexcr.2022.113085. Epub 2022 Mar 12.

Abstract

Background: The physical health and quality of life of the elderly are severely affected by osteoporosis (OP).

Methods: We explored the regulatory mechanism of ICA in vivo and in vitro by constructing OP rats and inducing osteogenic differentiation of BMSCs. First, we determined the expression of miR-335-5p in bone tissues of OP patients, bone tissues of OP rats, and osteogenic BMSCs by RT-qPCR. Alizarin red staining was employed to detect the formation of calcium nodules in the cells. MTT was used to detect cell viability. Finally, we detected the bone tissue changes in OP rats by overexpression of miR-335-5p or oral ICA.

Results: miR-335-5p was lowly expressed in bone tissues of OP patients and OP rats. ICA treatment reversed the inhibitory effect of miR-335-5p inhibitor on BMSCs matrix mineralization. Moreover, PTEN was verified to be a downstream effector of miR-335-5p. During ICA induction, overexpression of PTEN reversed the promotive effect of miR-335-5p mimics on the osteogenic differentiation of BMSCs. In vivo experiments also found that overexpression of miR-335-5p or ICA treatment improved the pathogenesis of OP in rats.

Conclusion: ICA improved OP by up-regulating miR-335-5p to inhibit PTEN, thereby providing a new strategy for the prevention and treatment of OP.

Keywords: BMSC; Icariin; Osteoporosis; PTEN; miR-335–5p.

MeSH terms

  • Aged
  • Animals
  • Bone Marrow Cells / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Flavonoids
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / metabolism
  • Osteogenesis / genetics
  • Osteoporosis* / drug therapy
  • Osteoporosis* / genetics
  • Osteoporosis* / metabolism
  • Quality of Life
  • Rats

Substances

  • Flavonoids
  • MIRN335 microRNA, human
  • MicroRNAs
  • icariin