Induction of Chondrocyte Apoptosis Following Impact Load

Borrelli, Joseph; Tinsley, Kevin W.; Ricci, William M.; Burns, Meghan; Karl, Irene E.; Hotchkiss, Richard

doi:10.1097/00005131-200310000-00006

Cited by 79 publications

(66 citation statements)

References 23 publications

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“…The lower threshold we observed might be related to the use of immature porcine cartilage explants. High mechanical stress can induce cell death (14,31), and the degree of chondrocyte death is related to the intensity of mechanical stress (32). Hashimoto et al showed that chondrocyte death occurred early during the process of cartilage degeneration in OA (9).…”

Section: Discussionmentioning

confidence: 99%

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

Otsuki¹,

Brinson²,

Creighton³

et al. 2008

Arthritis & Rheumatism

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Objective. Loss of glycosaminoglycan (GAG) is an early event in osteoarthritis. Recent findings showed increased cell death in arthritic cartilage and linkage with extracellular matrix degradation. The aim of this study was to analyze the direct effect of GAG loss on chondrocyte survival and cell death following mechanical injury.Methods. In full-thickness cartilage explants from porcine knee joints, GAG was depleted by digestion with chondroitinase ABC. Explants were subjected to single-impact mechanical injury. Cell viability and the types of cell death were analyzed by Live/Dead cell assay, staining for active caspase 3, and sensitivity to caspase inhibitor.Results. GAG depletion did not directly lead to increased cell death. In chondroitinase ABC-treated explants, but not in control explants, mechanical injury caused an immediate reduction in cell viability (from 84.6% to 71.0%); the reduction was prominent in the superficial zone. This immediate cell death was not inhibited by the pancaspase inhibitor Z-VAD-FMK, suggesting cell necrosis. During subsequent culture, viability in these explants decreased further, to 50.5% on day 3. The second wave of cell death was reduced by the addition of Z-VAD-FMK in chondroitinase ABC-treated explants and was also associated with activation of caspase 3, suggesting apoptotic mechanisms of cell death.Conclusion. These results indicate that GAG loss alone does not directly lead to chondrocyte death. In response to mechanical injury, there is an immediate induction of necrotic cell death that is seen only in GAG-depleted explants and primarily in the superficial zone. During subsequent culture, cell death spreads via apoptotic mechanisms.

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Section: Discussionmentioning

confidence: 99%

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

Otsuki¹,

Brinson²,

Creighton³

et al. 2008

Arthritis & Rheumatism

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“…Standard light microscopy is one of the most insensitive methods to detect apoptosis. However, in detecting lymphocyte apoptosis it is highly specific if certain morphologic changes are identified, and it has been used extensively in previous studies (37)(38)(39)(40). The morphologic changes specific to lymphocyte apoptosis consist of cell shrinkage with condensed nuclei (pyknosis) and nuclear fragmentation (karyorrhexis).…”

Section: Detection and Quantification Of Apoptosismentioning

confidence: 99%

Agonistic Monoclonal Antibody Against CD40 Receptor Decreases Lymphocyte Apoptosis and Improves Survival in Sepsis

Schwulst¹,

Grayson²,

DiPasco³

et al. 2006

The Journal of Immunology

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Sepsis causes a marked apoptosis-induced depletion of lymphocytes. The degree of lymphocyte apoptosis during sepsis strongly correlates with survival. CD40, a member of the TNFR family, is expressed on APCs and has potent antiapoptotic activity. In this study we determined whether an agonistic Ab against CD40 could protect lymphocytes from sepsis-induced apoptosis. Secondly, we examined potential antiapoptotic mechanisms of the putative protection. Lastly, we aimed to determine whether anti-CD40 treatment could improve survival in sepsis. CD1 mice were made septic by the cecal ligation and puncture method and treated postoperatively with anti-CD40 Ab. Treatment with anti-CD40 completely abrogated sepsis-induced splenic B cell death and, surprisingly, decreased splenic and thymic T cell death as well (p < 0.001). To investigate the mechanism of protection of anti-CD40 therapy on T cells, CD40 receptor expression was examined. As anticipated, the CD40 receptor was constitutively expressed on B cells, but, unexpectedly, splenic and thymic T cells were found to express CD40 receptor during sepsis. Furthermore, CD4+CD8− T cells were the predominant subtype of T cells expressing CD40 receptor during sepsis. Additionally, the antiapoptotic protein Bcl-xL was found to be markedly increased in splenic B and T cells as well as in thymic T cells after treatment with anti-CD40 Ab (p < 0.0025). Lastly, mice that were made septic in a double injury model of sepsis had improved survival after treatment with anti-CD40 as compared with controls (p = 0.05). In conclusion, anti-CD40 treatment increases Bcl-xL, provides nearly complete protection against sepsis-induced lymphocyte apoptosis, and improves survival in sepsis.

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“…It has been shown that mechanical injury to cartilage explants results in chondrocyte apoptosis with a loss of glycosaminoglycans [58] and changes in gene expression [59]. Similarly, Borelli Jr. et al [60] have shown that in vivo chondrocyte apoptosis can be caused by a single impact load. Furthermore in vitro chondrocyte necrosis can be induced by non-physiological stimuli [61].…”

Section: Discussionmentioning

confidence: 99%

Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

2013

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Induction of Chondrocyte Apoptosis Following Impact Load

Cited by 79 publications

References 23 publications

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

Agonistic Monoclonal Antibody Against CD40 Receptor Decreases Lymphocyte Apoptosis and Improves Survival in Sepsis

Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

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