Heterogeneous nuclear ribonucleoprotein A1 interacts with microRNA-34a to promote chondrogenic differentiation of mesenchymal stem cells.

The mesenchymal stem cell (MSC) shows potential in degenerative disc disease (DDD) treatment. However, little is known about the function of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in modulating the chondrogenic differentiation of MSCs. This study aimed to investigate the role of hnRNPA1 in the chondrogenic differentiation of MSCs and potential mechanisms. Mouse MSCs C3H10 and chondrogenic ATDC5 cells were used to quantify hnRNPA1 expression. The hnRNPA1 overexpression vectors were transfected into C3H10 cells, cell viability and chondrogenic factors expressions were assessed by MTT assay, qPCR and Western blot, respectively. After microRNA-34a (miR-34a) inhibitor transfection, expressions of chondrogenic factors and the Wnt signaling were detected. RNA-binding protein immunoprecipitation (RIP) was performed to reveal the interaction between hnRNPA1 and miR-34a. Results showed that hnRNPA1 was significantly down-regulated in C3H10 compared to ATDC5.Overexpression of hnRNPA1 markedly promoted C3H10 cell viability and expressions of chondrogenic factors SRY-box 9 (SOX9), collagen II, hyaluronan synthase 2 (HAS2) and aggrecan, without significant influence on adipogenic factors. miR-34a inhibitor suppressed chondrogenic factors expressions. RIP results showed the interaction between miR-34a and hnRNPA1. Besides, hnRNPA1 promoted expressions of Wnt family member 3A (WNT3A), WNT5A and β-catenin, and these effects were abrogated by miR-34a inhibitor. We fund the promotive effect of hnRNPA1 on chondrogenic factors, which might require the interaction with miR-34a and the regulation of the Wnt signaling. Thus hnRNPA1 might induce the chondrogenic differentiation of MSCs that facilitate the MSC therapy for DDD.