Oxygen and reactive oxygen species in cartilage degradation: friends or foes?  Y. Henrotin, Ph.D., B. Kurz, Ph.D., T. Aigner, M.D.DSc.  Osteoarthritis and Cartilage  Volume 13, Issue 8, Pages 643-654 (August 2005) DOI: 10.1016/j.joca.2005.04.002 Copyright © 2005 OsteoArthritis Research Society International Terms and Conditions

Fig. 1 HIF-1α oxygen-sensing pathways. In high oxygen tension, HIF-1α is hydroxylated allowing its binding to the von Hippel-Lindau (pVHL) tumor suppressor protein and subsequent enzymatic degradation. This reaction is catalyzed by prolyl hydroxylases (PHD). In low oxygen tension, HIF-1α cannot be degraded, translocates into the nucleus, forms a heterodimer with HIF-1β, which is constitutively expressed, and activates hypoxia-inducible target genes by binding to HIF-1 binding sites in hypoxia response elements (HRE) of the DNA (modified from Ref. 128). Osteoarthritis and Cartilage 2005 13, 643-654DOI: (10.1016/j.joca.2005.04.002) Copyright © 2005 OsteoArthritis Research Society International Terms and Conditions

Fig. 2 Schematic representation of the main sources of ROS in chondrocytes. NOS=nitric oxide synthase; MPO=myeloperoxidase, NO2−=nitrite; NO2=nitrosyl radical; ONOO−=peroxynitrite; OH=hydroxyl radical; O2−=superoxide anions; H2O2=hydrogen peroxide; HOCL=hypochlorite acid. Osteoarthritis and Cartilage 2005 13, 643-654DOI: (10.1016/j.joca.2005.04.002) Copyright © 2005 OsteoArthritis Research Society International Terms and Conditions

Fig. 3 Chondrocytes in OA cartilage are exposed to load, matrix destruction and mediators of various origins, all of which cause a structured reaction pattern, which might be either helpful for the tissue (e.g., anabolism) or even detrimental (e.g., cell death etc.). However, besides these structured processes, presumably a chaotic reaction pattern also occurs reflected in the microheterogeneity of cellular reaction pattern found in OA cartilage. Osteoarthritis and Cartilage 2005 13, 643-654DOI: (10.1016/j.joca.2005.04.002) Copyright © 2005 OsteoArthritis Research Society International Terms and Conditions