Inhibition of P‐glycoprotein facilitated glycosaminoglycan accumulation during chondrogenesis of human bone marrow mesenchymal stem cells

Abstract

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. 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). 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. 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.