Short-Term Exposure of Cartilage to Blood Results in Chondrocyte Apoptosis
Michel J. J. Hooiveld,Goris Roosendaal,M. J. G. Wenting,Marijke van den Berg,Johannes W. J. Bijlsma,Floris P J G Lafeber +5 more
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Data suggest that a single joint hemorrhage (a 4-day exposure of cartilage to 50% v/v blood) results in induction of chondrocyte apoptosis, responsible for the observed inability of the chonrocytes to restore the proteoglycan synthesis during recovery from a short-term exposure to blood.Abstract:
Studies have shown that joint bleeding leads to cartilage degradation independent of concurrent synovitis We hypothesized that the blood-induced cartilage damage is because of increased chondrocyte apoptosis after short-term exposure of whole blood or isolated mononuclear cells plus red blood cells to cartilage Human cartilage tissue samples were co-cultured for 4 days with whole blood (50% v/v) or with mononuclear cells plus red blood cells (50% v/v equivalents) Cartilage matrix proteoglycan synthesis ((35)SO(4)(2-) incorporation) was determined after 4 days as well as at day 16 (after a 12-day recovery period in the absence of any additions) To test the involvement of apoptosis a specific caspase-3 inhibitor (acDEVDcho, 0 to 500 micro mol/L) as well as a pan-caspase inhibitor (zVADfmk, 0 to 500 micro mol/L) were added Chondrocyte apoptosis was evaluated by immunohistochemical staining of single-strand DNA and by terminal dUTP nick-end labeling Cartilage co-cultured with whole blood as well as mononuclear cells plus red blood cells induced a long-term inhibition of proteoglycan synthesis (74% and 78% inhibition on day 16, respectively) Immunohistochemistry showed a threefold increase in apoptotic chondrocytes in cultures with 50% whole blood as well as with mononuclear cells plus red blood cells Both the specific caspase-3 inhibitor and the pan-caspase inhibitor partially restored proteoglycan synthesis in the cartilage after blood exposure This effect was accompanied by a decrease in the number of apoptotic chondrocytes These data suggest that a single joint hemorrhage (a 4-day exposure of cartilage to 50% v/v blood) results in induction of chondrocyte apoptosis, responsible for the observed inability of the chondrocytes to restore the proteoglycan synthesis during recovery from a short-term exposure to blood This reduced restoration could eventually lead to cartilage degeneration and ultimately joint destructionread more
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References
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Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis
TL;DR: Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.
Journal ArticleDOI
Mammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis
TL;DR: This work has shown that apoptotic cell death is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli, and that proteases play critical roles in initiation and execution of this process.
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Articular cartilage: tissue design and chondrocyte-matrix interactions.
TL;DR: The available evidence indicates that normal matrix turnover depends on the ability of chondrocytes to detect alterations in the macromolecular composition and organization of the matrix, including the presence of degraded molecules, and to respond by synthesizing appropriate types and amounts of new molecules.
Journal ArticleDOI
Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis.
TL;DR: Increased chondrocyte apoptosis and proteoglycan depletion are anatomically linked and may be mechanistically related.
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Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death.
TL;DR: Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, providing strong evidence that these are all bona fide examples of PCD.