Journal article
Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence
Biorheology (Oxford), Vol.41(3-4), pp.479-491
2004
PMID: 15299279
Abstract
Joint injuries frequently lead to progressive joint degeneration that causes the clinical syndrome of post-traumatic osteoarthritis. The pathogenesis of osteoarthritis remains poorly understood, but patient age is a significant risk factor for progressive joint degeneration. We have found that articular cartilage chondrocytes show strong evidence of senescence with increasing age, including synthesis of smaller more irregular aggrecans; increased expression of lysosomal beta-galactosidase and telomere erosion; and decreased proteoglycan synthesis, response to the anabolic cytokine IGF-I, proliferative capacity, and mitochondrial function. These observations help explain the strong association between age and joint degeneration, but they do not explain how joint injury increases the risk of joint degeneration in younger individuals. We hypothesized that excessive loading of articular surfaces due to acute joint trauma or post-traumatic joint instability, incongruity or mal-alignment increases release of reactive oxygen species, and that the increased oxidative stress on chondrocytes accelerates chondrocyte senescence thereby decreasing the ability of the cells to maintain or restore the tissue. To test this hypothesis, we exposed human articular cartilage chondrocytes from young adults to mechanical and oxidative stress. We found that shear stress applied to cartilage explants in a triaxial pressure vessel increased release of reactive oxygen species and oxidative stress induced chondrocyte senescence (as measured by expression of lysosomal beta-galactosidase, nuclear and mitochondrial DNA damage and decreased mitochondrial function). These observations support the hypothesis that joint injury accelerates chondrocyte senescence and that this acceleration plays a role in the joint degeneration responsible for post-traumatic osteoarthritis.
Details
- Title: Subtitle
- Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence
- Creators
- James A Martin - Department of Orthopaedics, University of Iowa, Iowa City, IA 52242, USAThomas BrownAnneliese HeinerJoseph A Buckwalter
- Resource Type
- Journal article
- Publication Details
- Biorheology (Oxford), Vol.41(3-4), pp.479-491
- PMID
- 15299279
- NLM abbreviation
- Biorheology
- ISSN
- 0006-355X
- eISSN
- 1878-5034
- Publisher
- Netherlands
- Grant note
- P50 AR48939 / NIAMS NIH HHS
- Language
- English
- Date published
- 2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040433002771
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