Midkine-deficiency increases the anabolic response of cortical bone to mechanical loading

► Increased bone formation in midkine (Mdk)-deficient mice in response to mechanical load. ► Mdk has a negative effect on β-catenin-dependent Wnt signaling. ► The extent of this negative effect appears to be dependent on Ptprz expression. ► Mdk decreases Wnt target gene expression in non-loaded and loaded osteoblasts.