Inhibition of Paglycoprotein facilitated glycosaminoglycan accumulation during chondrogenesis of human bone marrow mesenchymal stem cells

Aim: 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. Method: BM-MSCs were isolated from 16 volunteers after informed consent and incubated for 28days using three-dimensional culture methods in chondrogenic medium with and without P-gp inhibitor (verapamil, 10 mu mol/L). Results: Hematoxylin and eosin staining revealed a cartilaginous structure with chondrogenic cells in the lacunae after 2weeks 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. Conclusion: 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.