title: Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study.
abstract: 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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.
authors.affiliation: Department of Orthopedics, Pu-Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Z-B
authors.initials: ZB
authors.lastname: Sun
authors.forename: J-W
authors.initials: JW
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Xiao
authors.forename: Q-S
authors.initials: QS
authors.lastname: Zhang
authors.forename: W-S
authors.initials: WS
authors.lastname: Kan
authors.forename: F-B
authors.initials: FB
authors.lastname: Mo
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: S-N
authors.initials: SN
authors.lastname: Ye
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D010012:Osteogenesis / Q000187:drug effects; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D005938:Glucocorticoids; D017382:Reactive Oxygen Species; C056599:icariin
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