UNC-5 netrin receptor B regulates adipogenesis of human adipose-derived stem cells through JNK pathway.

ABSTRACT

BACKGROUND: There is a balance between adipogenic differentiation and osteogenic differentiation of human adipose-derived stem cells (hASCs). It is essential to explore the mechanism of hASCs lineage commitment. In our previous study, UNC-5 netrin receptor B (UNC5B) was identified as a positive regulator for osteogenesis. OBJECTIVE: To further explore the potential roles and mechanisms of UNC5B during adipogenic differentiation and to provide a new method to regulate adipogenesis and osteogenesis of hASCs. METHODS: Lentivirus containing UNC5B shRNA was used for UNC5B knockdown. Plasmids overexpressing UNC5B gene were used for UNC5B upregulation. To investigate the role of UNC5B in adipogenesis in vitro and in vivo, Oil Red O staining, RT-qPCR and transplantation into nude mice were performed. Western blotting analyses were performed to explore the mechanisms of UNC5B in adipogenic differentiation. RESULTS: UNC5B expression in hASCs was significantly increased during adipogenic differentiation. Knockdown of UNC5B enhanced adipogenic differentiation in vitro. Both H&E staining and Oil Red O staining showed more adipose tissue-like constructs in UNC5B-knockdown cells in vivo. Upregulation of UNC5B significantly impaired adipogenic differentiation in vitro. Downregulation of UNC5B could increase phosphorylation of JNK in hASCs. JNK inhibitors reduced adipogenic differentiation of hASCs. CONCLUSION: Our findings showed that UNC5B inhibited adipogenesis of hASCs through JNK signalling. As a whole, UNC5B regulates both adipogenesis and osteogenesis of hASCs.