Higher expression of the type I receptor ALK2 in high-grade chondrosarcoma could however contribute to enhanced BMP signaling and phosphorylated Smad1/5/8 in these tumors compared to grade I. On the other hand, Smad1/5/8 can also be activated by TGFβ driven ALK1 activation as it has been shown in endothelial cells, neurons, hepatic stellate cells and chondrocytes [7]. This evidence concerns the gene ACVR1 and chondrosarcoma.