Oxidative stress induces senescence in chondrocytes

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 p...

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Published in:Journal of orthopaedic research 2011-07, Vol.29 (7), p.1114-1120
Main Authors: Brandl, Anita, Hartmann, Andreas, Bechmann, Volker, Graf, Bernhard, Nerlich, Michael, Angele, Peter
Format: Article
Language:English
Subjects:
Adult
Aged
Cartilage, Articular - cytology
Cell Division - drug effects
Cell Division - physiology
Cells, Cultured
cellular senescence
Cellular Senescence - drug effects
Cellular Senescence - physiology
Chondrocytes - cytology
Chondrocytes - drug effects
Chondrocytes - metabolism
DNA damage
DNA Damage - genetics
DNA Repair - genetics
human chondrocytes
Humans
Hydrogen Peroxide - pharmacology
Middle Aged
Oxidants - pharmacology
oxidative stress
Oxidative Stress - drug effects
Oxidative Stress - physiology
Telomere - drug effects
Telomere - genetics
Telomere - physiology
telomeres
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Summary: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. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1114–1120, 2011
ISSN:0736-0266
1554-527X
DOI:10.1002/jor.21348