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

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 hASC 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 containingUNC5BshRNA was used forUNC5Bknockdown. Plasmids overexpressingUNC5Bgene were used forUNC5Bupregulation. 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 ofUNC5Benhanced adipogenic differentiation in vitro. Both H&E staining and Oil Red O staining showed more adipose tissue-like constructs inUNC5B-knockdown cells in vivo. Upregulation of UNC5B significantly impaired adipogenic differentiation in vitro. Downregulation ofUNC5Bcould 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.