title: Oxidative stress induces senescence in chondrocytes.
abstract: Cellular senescence is a program activated during diverse situations of cell stress. Chondrocytes differ from other somatic cells as articular cartilage is an avascular tissue. The effects of oxidative stress on chondrocytes are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of human osteoarthritic chondrocytes, subjected to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by RT-PCR. Sub-lethal doses of oxidative stress induced cell-cycle arrest, senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged oxidative treatment had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. The effects of sub-lethal oxidative stress regarding proliferation and telomere biology were more distinct in senescent cells. Acute oxidant insult caused up-regulation of p21 expression to levels comparable to senescent cells. TRF2 protects telomere ends and showed elevated expression levels. SIRT1 and XRCC5 enable cells to cope with unfavorable growing conditions. Both were up-regulated after oxidant insult, but expression levels decreased in aging cells. Taken together, oxidative stress considerably accelerated telomere shortening and cellular aging in chondrocytes. Senescent cells showed a reduced tolerance to oxidative stress.
authors.affiliation: Department of Anesthesiology, University Hospital Regensburg, 93042 Regensburg, Germany. anita.brandl@klinik.uni-regensburg.de
authors.forename: Anita
authors.initials: A
authors.lastname: Brandl
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.forename: Volker
authors.initials: V
authors.lastname: Bechmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Graf
authors.forename: Michael
authors.initials: M
authors.lastname: Nerlich
authors.forename: Peter
authors.initials: P
authors.lastname: Angele
mesh_terms: D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016615:Telomere / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide