Chondrocyte apoptosis induced by hydrogen peroxide requires caspase activation but not mitochondrial pore transition

Lo, Marvin Y; Kim, Hubert T.

doi:10.1016/j.orthres.2003.12.022

Cited by 35 publications

(24 citation statements)

References 25 publications

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“…In a previous study, we have shown that maturing chondrocytes generate ROS (Matsumoto et al, 1991); moreover, in many tissues including cartilage, H 2 O 2 is a potent physiological apoptogen (Lo and Kim, 2004). One mechanism by which cells protect themselves from ROS is through expression of catalase and SOD, two powerful dismutating enzymes (Valko et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Terkhorn

Bohensky

Shapiro

et al. 2006

Journal Cellular Physiology

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The overall goal of the current study was to examine the functional activity of the prolyl hydroxylases (PHDs) in maturing chondrocytes. Herein, we show for the first time that the PHDs are expressed in the maturing zone of the growth plate, and by a chondrocytic cell line. We determined if this protein and its substrate, hypoxia inducible factor (HIF)-1a, modulated the induction of apoptosis. Using a chondrocyte cell line that matured in culture, we inhibited HIF-1a expression using siRNA technology and pharmacologically blocked PHD activity. We noted that PHD suppression sensitized the cells to an apoptotic challenge with H 2 O 2 . We next examined the interplay between the PHDs and HIF-1a by suppressing HIF-1a and blocking PHD activity. We noted reduced killing when the mature HIF-silenced cells were challenged with H 2 O 2 . In contrast, there was limited change in the viability of immature cells. Based on these differences in chondrocyte susceptibility, it is concluded that HIF-1a sensitizes maturing cells to H 2 O 2 -mediated killing. We next determined if this change in the viability of the PHD-inhibited cells was linked to changes in activation of caspase-3. It was noted that there was a minimal change in enzyme activity of the PHD-inhibited HIF-1a suppressed cells. Finally, we found that as the chondrocytes mature, the activities of catalase and SOD were significantly reduced and that there was a decrease in the levels of Bcl-2 and Bcl XL . This loss of protective activity together with the changes mediated by HIF would be expected to generate conditions that would favor the induction of chondrocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Terkhorn

Bohensky

Shapiro

et al. 2006

Journal Cellular Physiology

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“…20,21 H 2 O 2 at mM concentrations has been shown to induce apoptosis in cartilage. 22 Treatment of chondrocytes with 50-100 μM H 2 O 2 for one day was reported to induce the transcription factor activator protein 1 and to up-regulate matrix metalloproteinase 3 expression. 23 We showed the up-regulated metalloproteinase mechanism for ADAMTS9 expression at a higher concentration of H 2 O 2 in this study.…”

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confidence: 99%

Hydrogen Peroxide-Induced Oxidative Damage in Human Chondrocytes: The Prophylactic Effects of Hypericum Perforatum Linn Extract on Deoxyribonucleic acid Damage, Apoptosis and Matrix Remodeling by a Disintegrin-Like and Metalloproteinase With Thrombospondin Motifs Proteinases

et al. 2014

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Objectives: This in vitro study aimed to examine the protective roles of Hypericum perforatum Linn (HPL) extract on cell viability, DNA damage, apoptosis and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) proteins in chondrocytes induced by hydrogen peroxide (H2O2), as a model of chondrocytes subjected to reactive oxygen species (ROS) attack in rheumatoid arthritis and osteoarthritis. Materials and methods: Human chondrosarcoma cell line (OUMS-27) was used. Cells were incubated with different concentrations of methanolic extract (100, 400, and 750 μg/ml) of HPL for 36 hours, and then treated with 0.7 mM H2O2 for two hours. Trypan blue was used for evaluation of cell viability, while DNA damage was evaluated by alkaline Comet assay. Caspase-1, ADAMTS5, ADAMTS9, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins were analyzed by Western blot. Results: In vitro H2O2 treatment decreased OUMS-27 cell viability. Cells pretreated with HPL at concentration of 400 μg/mL were best protected from H2O2 toxicity. Compared to 100 μg/ml concentration, pretreatment of cells with 750 or 400 μg/ml of HPL generated more protection against H2O2-induced DNA damage. Hydrogen peroxide application to the cells led to a slight increase in Caspase-1 expression, which shows no apoptosis. The most prominent increase in Caspase-1 level was shown in cells treated with 400 μg/ml of HPL extract. There was an increase in ADAMTS9 and a decrease in ADAMTS5 levels upon H2O2 administration. Pretreatment with HPL led to more decrease in ADAMTS5 level, indicating the protection of extracellular matrix attacked by these proteinases in cartilage tissue. Conclusion: It can be concluded that HPL has a potential to reverse the negative effects and processes induced by H2O2 in OUMS-27 cells and it can protect the surrounding cartilage area of chondrocytes from oxidative damage, which is suggested to be one of the main molecular factors accused for progression of rheumatoid arthritis and osteoarthritis.

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“…This is supported by a study of Lo and Kim that demonstrated apoptosis of chondrocytes after incubation of different concentrations of hydrogen peroxide. The data showed apoptotic cells after six hours incubation time at a concentration of 4 mM hydrogen peroxide [17].…”

Section: Discussionmentioning

confidence: 95%

Toxicity of antiseptics against chondrocytes: What is best for the cartilage in septic joint surgery?

Röhner

Kolar

Seeger

et al. 2011

International Orthopaedics (SICOT)

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In septic joint surgery, the most frequently used antiseptics are polyhexanide, hydrogen peroxide and taurolidine. The aim of this study was to examine the effects of these antiseptics on viability of human chondrocytes. Our hypothesis was that antiseptics and supplemental irrigation with sodium chloride lavage are less toxic on human chondrocytes than treatment with antiseptics only. Primary human chondrocytes were isolated and cultured from six donated human knee joints. Polyhexanide, hydrogen peroxide or taurolidine were added to the cultures. Toxicity analysis was performed by visualisation of cell structure using light microscopy and LDH activity. The determination of vital cells and total cell numbers of chondrocytes treated with antiseptics partly followed by irrigation with sodium chloride solution was performed by using Casy Cell-Counter. Light microscopic data revealed a defect in cell structure after addition of antiseptics. We showed a significant increase of LDH enzyme activity after the treatment with polyhexanide or taurolidine. After treatment with antiseptics followed by sodium chloride solution a significant increase of vital and total cell numbers resulted in comparison with the chondrocytes that were only treated with antiseptics. The data show that treatment with polyhexanid, hydrogen peroxide or taurolidine induces cell death of human chondroctes in vitro. The application of sodium chloride solution after the treatment with polyhexanide and hydrogen peroxide possibly has a protective effect on chondrocyte viability.

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Chondrocyte apoptosis induced by hydrogen peroxide requires caspase activation but not mitochondrial pore transition

Cited by 35 publications

References 25 publications

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity

Hydrogen Peroxide-Induced Oxidative Damage in Human Chondrocytes: The Prophylactic Effects of Hypericum Perforatum Linn Extract on Deoxyribonucleic acid Damage, Apoptosis and Matrix Remodeling by a Disintegrin-Like and Metalloproteinase With Thrombospondin Motifs Proteinases

Toxicity of antiseptics against chondrocytes: What is best for the cartilage in septic joint surgery?

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