Melatonin-mediated Inhibition of XPO5 phosphorylation facilitates the chondrogenic differentiation of human bone marrow mesenchymal stem cells by regulating the transport of miR-590-5p

Objective: Osteoarthritis is a prevalent chronic degenerative joint disease, and repairing cartilage damage remains a major clinical challenge. Hence, this study was recruited to discuss the effects and underlying mechanisms of melatonin (MLT) on the chondrogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) in vitro.

Methods: Human BMSCs were treated with MLT to assess miR-590-5p expression levels. After inducing chondrogenic differentiation in BMSCs, Alcian blue staining was conducted to evaluate chondrogenesis. Next, the expression levels of osteogenesis-associated Collagen type II (COL2A1), aggrecan (ACAN), sex-determining region Y-box 9 (SOX9), as well as extracellular signal-regulated kinase (ERK) exportin-5 (XPO5) pathway-related proteins, were tested by real-time fluorescence quantitative polymerase chain reaction and western blot. Subsequently, RNA immunoprecipitation was performed to analyze the interaction between XPO5 and pre-miR-590-5p.

Results: MLT promoted chondrogenic differentiation of BMSCs and up-regulated miR-590-5p expression, as well as COL2A1, ACAN, and SOX9 levels. However, miR-590-5p inhibition reversed these effects and down-regulated COL2A1, ACAN, and SOX9. Additionally, MLT inhibited XPO5 and ERK phosphorylation, promoting the nuclear transport of pre-miR-590-5p, which binds to XPO5.

Conclusion: MLT promotes the chondrogenic differentiation of BMSCs by regulating miR-590-5p transport through the inhibition of the ERK/XPO5 pathway, offering new therapeutic insights for cartilage damage-related diseases such as osteoarthritis.

Bone marrow mesenchymal stem cell; Exportin-5; Melatonin; miR-590-5p.