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Inhibition of P-glycoprotein facilitated glycosaminoglycan accumulation during chondrogenesis of human bone marrow mesenchymal stem cells
Authors:Kim Sang-Gyung  Lee A-Jin  Lee Seung Jin  Suh Hun Suk  Shin Im-Hee
Affiliation:Department of Laboratory, Catholic University of Daegu, School of Medicine, Daegu, Korea.
Abstract: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 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. 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.
Keywords:chondrogenesis  extracelullar matrix  mesenchymal stem cell  P‐glycoprotein
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