Figure 3.

Friend pathways. During moderate hypoxia, the friend role of HIF-1α is increasingly reinforced as oxygen tension gradually decreases. There are a number of pathways in this process, but the end point is the upregulation of ECM synthesis. HIF-1α, hypoxia-inducible factor-1α; ECM, extracellular matrix; PKM2, pyruvate kinase M2; GLUT-1, glucose transporter 1; PHD3, prolyl hydroxylase 3; VEGF, vascular endothelial growth factor; INF-1, eukaryotic initiation factor 4A; MMPS, matrix metalloproteinases; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; BNIP3, BCL2 interacting protein 3; TGF-β, transforming growth factor-β; IVD, intervertebral disc; ANK/ANKH, progressive ankylosis; Gal-3, galectin 3; CEC, cartilage endplate calcification; CA, carbonic anhydrase.