Oxidative Stress Induces Senescence in Chondrocytes

Brandl, Anita and Hartmann, Andreas and Bechmann, Volker and Graf, Bernhard and Nerlich, Michael and Angele, Peter (2011) Oxidative Stress Induces Senescence in Chondrocytes. JOURNAL OF ORTHOPAEDIC RESEARCH, 29 (7). pp. 1114-1120. ISSN 0736-0266,

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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 beta-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 sublethal 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. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1114-1120, 2011

Item Type: Article
Uncontrolled Keywords: HUMAN-DIPLOID FIBROBLASTS; CELLULAR SENESCENCE; TELOMERE LENGTH; HUMAN-CELLS; DNA-REPAIR; XRCC GENES; IN-VITRO; CARTILAGE; DAMAGE; COMPLEX; cellular senescence; oxidative stress; telomeres; DNA damage; human chondrocytes
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Medicine > Lehrstuhl für Unfallchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Jun 2020 06:24
Last Modified: 09 Jun 2020 06:24
URI: https://pred.uni-regensburg.de/id/eprint/20640

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