title: Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence.
abstract: Senescence compromises the ability of chondrocytes to maintain and repair articular cartilage. We hypothesized that oxidative stress and telomere loss contribute to chondrocyte senescence. To test this hypothesis, we compared the growth of human articular cartilage chondrocytes incubated in 5% O2 and 21% O2. Cells grown in 5% O2 reached 60 population doublings (PD) before senescing, but growth in 21% O2 induced DNA damage and premature senescence at less than 40 PD. Human telomerase reverse transcriptase (hTERT)-transduction failed to prevent chondrocyte senescence in 21% O2, but allowed 1 of 3 chondrocyte strains to exceed 90 PD in 5% O2. These results show that oxidative stress causes premature chondrocyte senescence. They may help explain the increased risk of osteoarthritis with age and after joint trauma and inflammation, and suggest that minimizing oxidative damage will help produce optimal results for chondrocyte transplantation.
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
authors.forename: Aloysius J
authors.initials: AJ
authors.lastname: Klingelhutz
authors.forename: Farid
authors.initials: F
authors.lastname: Moussavi-Harami
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Buckwalter
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000704:Analysis of Variance; D015139:Blotting, Southern; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology*; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology*; D020552:Comet Assay; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D008938:Mitosis; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D019098:Telomerase; D001616:beta-Galactosidase; D010100:Oxygen