Volume 5 Supplement 3
Oxidative stress induces chondrocyte telomere instability and chondrocyte dysfunctions in osteoarthritis
© BioMed Central Ltd 2003
Published: 12 September 2003
To clarify the implication of oxidative stress in the progression to osteoarthritis (OA) from the point of view of oxygen free radical-induced genomic instability, including telomere instability and resultant replicative senescence and dysfunction in human chondrocytes.
Human chondrocytes and articular cartilage explants were isolated from knee joints in patients undergoing arthroplastic knee surgery for OA. The oxidative damage/antioxidative capacity in OA cartilage was investigated in the donor-matched pairs of the intact and degenerative region that were isolated from same OA cartilage explants. The results were histologically confirmed by immunohistochemistry for nitrotyrosine, which has been considered a maker of oxidative damage. Under treatment with reactive oxygen species or antioxidative agent (ascorbic acid), cellular replicative potential, telomere instability and production of proteoglycan aggrecan glycosaminoglycan (GAG) were assessed in cultured chondrocytes.
Lower capacity of antioxidant and stronger staining of nitrotyrosine were observed in the degenerative regions of OA cartilages as compared with those of intact regions from the same cartilage explants. Immunopositivity for nitrotyrosine was associated with the grade of histologic change of OA cartilage, suggesting the correlation of oxidative damage with articular cartilage degeneration. During continuous culture of chondrocytes, the telomere length, replicative capacity and GAG production were decreased by treatment with reactive oxygen species. In contrast, treatment with an antioxidative agent showed a tendency to elongate the telomere length and replicative lifespan in cultured chondrocytes.
Our findings clearly showed the presence of oxidative stress that induces telomere genomic instability, replicative senescence and dysfunction of chondrocytes in OA cartilage, suggesting the implication of oxidative stress in the chondrocyte senescence and cartilage aging responsible for the development of OA. New efforts to prevent the development and progression of OA may include the strategies and interventions aimed at reducing oxidative damage in articular cartilage.