Reactive oxygen species (ROS) are implicated in both cartilage aging and the pathogenesis of osteoarthritis. We developed an in vitro model to study the role of chondrocyte-derived ROS in cartilage matrix protein degradation. Matrix proteins in cultured primary articular chondrocytes were labeled with [ 3 H]proline, and the washed cell matrix was returned to a serum-free balanced salt solution. Exposure to hydrogen peroxide resulted in oxidative damage to the cell matrix as established by monitoring the release of labeled material into the medium. Calcium ionophore treatment of chondrocytes, in a dose-dependent manner, significantly enhanced the release of labeled matrix, suggesting a chondrocyte-dependent mechanism of matrix degradation. Antioxidant enzymes such as catalase or superoxide dismutase did not influence matrix release by the calcium ionophore-activated chondrocytes. However, vitamin E, at physiological concentrations, significantly diminished the release of labeled matrix by activated chondrocytes. The fact that vitamin E is a chain-breaking antioxidant indicates that the mechanism of matrix degradation and release is mediated by the lipid peroxidation process. Lipid peroxidation was measured in chondrocytes loaded with cis-parinaric acid. Both resting and activated cells showed constitutive and enhanced levels of lipid peroxidation activity, which were significantly reduced in the presence of vitamin E. In an immunoblot analysis, malondialdehyde and hydroxynonenal adducts were observed in chondrocyte-matrix extracts, and the amount of adducts increased with calcium ionophore treatment. Furthermore, vitamin E diminished aldehyde-protein adduct formation in activated extracts, which suggests that vitamin E has an antioxidant role in preventing protein oxidation. This study provides in vitro evidence linking chondrocyte lipid peroxidation to cartilage matrix protein (collagen) oxidation and degradation and suggests that vitamin E has a preventive role. These observations indicate that chondrocyte lipid peroxidation may have a role in the pathogenesis of cartilage aging and osteoarthritis.Cartilage degeneration is a hallmark of cartilage aging and osteoarthritis (1). Degeneration of articular cartilage in osteoarthritis is accompanied by chronic pain and significant disability. In a series of reports (2-7), we and others have documented that chondrocytes produce reactive oxygen species (ROS).1 The production of ROS by chondrocytes can contribute to degradation of the cartilage matrix. For example, ROS can mediate intracellular signaling and gene activation of cytokine and growth factor-induced products in chondrocytes (8, 9). In activated neutrophils and monocytes/macrophages, the cellspecific gene products of "NADPH-oxidase complex" physically come together and initiate single electron reduction of oxygen and the release of ROS outside the cells. Phagocytes use the toxic properties of ROS to eliminate pathogens (10, 11); in contrast, the biological role of secreted ROS in cartilage is not known.The ob...
These observations suggest that collagen hydroxylation of matrix by vitamin C does not play a role in this model of chondrocyte-dependent collagen degradation. Also, this study demonstrates that chondrocyte-derived lipid peroxidation product MDA mediates oxidation of cartilage collagens. Oxidative modification of cartilage collagen in vivo could result in alteration of biochemical and biophysical properties of cartilage collagen fibrils, making them prone to degradation, thus initiating the changes observed in aging and OA.
Osteonecrosis has been increasingly associated with HIV disease throughout the 1990s, and the incidence appears to be rising. The hip is most commonly involved and often bilaterally. Although anecodotal reports suggest an association between osteonecrosis and highly active antiretroviral therapy, controlled epidemiologic studies do not support a direct link. Many patients with osteonecrosis have established risk factors, some of which may be related to HIV disease or its therapy, including corticosteroid use and hyperlipidemia. Alcoholism, hypercoagulability, megesterol acetate use, immune reconstitution, and other factors may also contribute. Plain radiographs and magnetic resonance imaging are the cornerstones of diagnosis. Management is dependent on the stage of bone disease and ranges from observation to total joint arthroplasty. Clinicians may help to prevent HIV-associated osteonecrosis by encouraging patients to limit their exposure to the established risk factors for the disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.