title: Inhibition of P-glycoprotein facilitated glycosaminoglycan accumulation during chondrogenesis of human bone marrow mesenchymal stem cells.
abstract: OBJECTIVE
  P-glycoprotein (P-gp) is an adenosine-5-triphosphate Binding Cassettes B 1 (ABCB1) transporter that exports various substrates on cellular membrane. Surface expression of P-gp was decreased during chondrogenesis of human bone marrow mesenchymal stem cells (BM-MSCs). We examined the role of P-gp in extracellular matrix deposition during chondrogenesis of human BM-MSCs.
  
  
  METHODS
  BM-MSCs were isolated from 16 volunteers after informed consent and incubated for 28 days using three-dimensional culture methods in chondrogenic medium with and without P-gp inhibitor (verapamil, 10 μmol/L).
  
  
  RESULTS
  Hematoxylin and eosin staining revealed a cartilaginous structure with chondrogenic cells in the lacunae after 2 weeks of culture. Total glycosaminoglycan (GAG) content was increased and rose during pellet culture. Hyaluronan (HA) content of the culture medium decreased with P-gp inhibitor. Type II collagen deposition decreased with P-gp inhibitor.
  
  
  CONCLUSIONS
  Inhibition of P-gp facilitated GAG accumulation via HA export inhibition during chondrogenic differentiation of human BM-MSCs. Modulation of P-gp expression during chondrogenesis would be a possible therapeutic approach for articular cartilage regeneration.
authors.affiliation: Department of Laboratory, Catholic University of Daegu, School of Medicine, Daegu, Korea.
authors.forename: Sang-Gyung
authors.initials: SG
authors.lastname: Kim
authors.forename: A-Jin
authors.initials: AJ
authors.lastname: Lee
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hun Suk
authors.initials: HS
authors.lastname: Suh
authors.forename: Im-Hee
authors.initials: IH
authors.lastname: Shin
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D024043:Collagen Type II / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D024043:Collagen Type II; D006025:Glycosaminoglycans; D006820:Hyaluronic Acid; D014700:Verapamil