Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study

Z. B. Sun, J. W. Wang, H. Xiao, Q. S. Zhang, W. S. Kan, F. B. Mo, S. Hu*, S. N. Ye

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

55 Scopus citations

Abstract

Summary: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH.

Introduction: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation.

Methods: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin.

Results: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis.

Conclusion: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalOsteoporosis International
Volume26
Issue number1
DOIs
StatePublished - 01 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.

Keywords

  • ABCB1
  • Hypermethylation
  • Icariin
  • Steroid-associated osteonecrosis

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