Fibronectin type III domain containing four promotes differentiation of C2C12 through the Wnt/β-catenin signaling pathway.

Fibronectin type III domain containing 4 (FNDC4) belongs to the fibronectin type III domain containing protein family. FNDC5, which is highly homologous to FNDC4, can promote the differentiation of cardiac cells. We aimed to investigate the role of FNDC4 in the differentiation of C2C12 mouse skeletal muscle cells. Western blotting and immunofluorescence analysis showed that FNDC4 gradually increased with the differentiation of C2C12. Muscle injury repair experiments indicated that FNDC4 may promote the repair of injured muscles. When FNDC4 was either overexpressed or knocked down, the expression of desmin and myogenin myogenic marker molecules followed that of FNDC4, suggesting that FNDC4 can influence the differentiation of C2C12. In addition, immunoprecipitation results showed that FNDC4 can interact with the Wnt/β-catenin signaling pathway receptor low-density lipoprotein receptor-related protein 6 (LRP6), and that β-catenin levels in the nucleus decreased after knocking down FNDC4. Exogenous addition of FNDC4 protein could not restore the blocking of differentiation due to inhibition of both Wnt/β-catenin signal transduction and LRP6 activity via the β-catenin inhibitor XAV-939. Overall, our findings indicate that FDNC4 can influence the differentiation of C2C12 by activating Wnt/β-catenin signal transduction.