Book chapter
Potential Mechanisms of PTA: Oxidative Stress
Post-Traumatic Arthritis, pp.211-219
Springer US
01/01/2015
DOI: 10.1007/978-1-4899-7606-2_17
Abstract
Oxidative insults to articular cartilage during and after joint injuries have long been implicated in the pathogenesis of post-traumatic arthritis (PTA). Acute oxidant overexposure kills chondrocytes in newly injured cartilage, and chondrocytes under chronic oxidative stress display metabolic abnormalities that interfere with the synthesis and export of extracellular matrix (ECM) proteins. Concomitantly, the ATP that fuels ECM production may become scarcer as cells devote more resources to antioxidant defenses. Collectively these effects are potentially destabilizing to cartilage, but their significance in the complex pathogenesis of PTA is uncertain. Although antioxidants have shown some disease-modifying activity in animal models of PTA, relatively few studies support efficacy in humans, and those studies showing positive results are counterbalanced by others that show no effect. These equivocal findings have raised skepticism in some quarters regarding the future of antioxidants as therapies for osteoarthritis. Meanwhile, however, we have acquired better knowledge of oxidant metabolism in chondrocytes that may allow for the development of more successful interventions. In that regard, recently published work indicates that oxidative stress in chondrocytes arises as a direct consequence of mechanical overloading of cartilage. These data indicate that overloading activates a chondro-specific mechanotransduction pathway that produces intracellular oxidants in response to deformation of the cartilage ECM. The pathway is calibrated such that physiologic loading results in healthy redox balance in chondrocytes, while overloading results in oxidative stress or death. Joint overloading and overuse are major pathogenic factors in OA that were not formerly thought to be subject to pharmacologic intervention, but current knowledge suggests that drugs that inhibit the chondrocyte’s oxidant production pathway can mitigate the harm done by overloading.
Details
- Title: Subtitle
- Potential Mechanisms of PTA: Oxidative Stress
- Creators
- Mitchell C Coleman - University of IowaJoseph A Buckwalter - University of IowaJames A Martin - University of Iowa
- Resource Type
- Book chapter
- Publication Details
- Post-Traumatic Arthritis, pp.211-219
- DOI
- 10.1007/978-1-4899-7606-2_17
- Publisher
- Springer US; Boston, MA
- Language
- English
- Date published
- 01/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology; Injury Prevention Research Center
- Record Identifier
- 9984242325802771
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