Wnt4 Inhibits Osteogenesis Of JBMMSCs In T2DM

This study aimed to determine whether Wnt4 was related to the T2DM-induced osteogenesis suppression of JBMMSCs and uncover the underlying regulating mechanism. GK rats were used as the T2DM model and Wistar rats as the control. JBMMSCs were isolated by combining bone marrow flashing and bone slice digestion under sterile conditions. Cell surface markers and stemness of JBMMSCs were compared by flow cytometry and in vitro differentiation respectively. The related genes’ mRNA and protein expression levels were compared using qRT-PCR and Western blot. ALP staining and alizarin red staining were used to compare ALP expression and calcium nodule formation. There was no significant difference in cell morphology and immunophenotype between Wistar-JBMMSCs and GK-JBMMSCs. T2DM suppressed the proliferation, clone-formation, and differentiation ability of JBMMSCs. The mRNA and protein expression levels of Wnt4 were higher in diabetic JBMMSCs. Overexpression of Wnt4 could inhibit the osteogenic ability of T2DM-derived JBMMSCs and inhibition of the p38MAPK signaling pathway attenuated the negative effect of Wnt4 on the osteogenic differentiation of JBMMSCs. Under the influence of T2DM, Wnt4 inhibited the osteogenic ability of JBMMSCs through the non-canonical Wnt/p38MAPK signaling pathway.