The Contributive Role of IGFBP-3 and Mitochondria in Synoviocyte-Induced Osteoarthritis through Hypoxia/Reoxygenation Injury: A Pathogenesis-Focused Literature Review

Figure 5

Hypoxia regulation of the cell death pathway (reprinted from Harris [72] and reused with permission from Springer Nature under license number 4820081324341). HIF-1 (a complex of HIF-1α and ARNT) activates transcription of many proapoptotic genes including IGFBP-3. HIF-1 activates the transcriptional activity of p53 and induces transcription of BAX. In turn, BAX promotes release of cytochrome c and promotes apoptosis via cascade reactions. Abbreviations: APAF-1: apoptotic protease-activating factor-1; ARNT: aryl hydrocarbon receptor nuclear translocator; HIF: hypoxia-inducible factor; IGF-1: insulin-like growth factor-1; IGF-1R: IGF-1 receptor; IGFBP-3: IGF binding protein 3; PI3K: phosphatidylinositol 3-OH kinase.