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Loss of chondrogenic potential in dedifferentiated chondrocytes correlates with deficient Shc-Erk interaction and apoptosis.

Schulze-Tanzil, G, Mobasheri, A, de Souza, P, John, T and Shakibaei, M (2004) Loss of chondrogenic potential in dedifferentiated chondrocytes correlates with deficient Shc-Erk interaction and apoptosis. Osteoarthritis Cartilage, 12 (6). pp. 448-458.

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OBJECTIVE: If dedifferentiated chondrocytes could be induced to redifferentiate in vitro, then we might thereby be furnished with a population of phenotypically stable cells for autologous implantation in reconstructive surgery. We therefore investigated the redifferentiation capabilities of chondrocytes which, having migrated from alginate beads to form a monolayer, were subsequently passaged. We also characterized the molecular traits of irreversibly dedifferentiated cells. METHODS: Human chondrocytes that had migrated from alginate beads to form a monolayer (passage 1) were passaged seven times (passages 2-8). Cells from each passage were then recultivated in alginate beads. We assessed the synthesis of type-II collagen, cartilage-specific proteoglycans, adhesion molecules (integrins), signaling proteins (Src-homology collagen [Shc] and extracellular-signal-regulated kinase [Erk]) and the apoptosis marker 'activated' caspase-3 in monolayer or secondary alginate cultures. RESULTS: The synthesis of cartilage-specific type-II collagen, alpha 3-integrin, Shc and activated Erk1/2 decreased rapidly after four passages in monolayer culture. Up to passage 4, cells redifferentiated in alginate culture. However, between passages 5 and 8, cells began to produce activated caspase-3; these cells not only failed to redifferentiate when recultivated in alginate, but underwent apoptosis. CONCLUSION: We conclude that the loss of chondrogenic potential by chondrocytes maintained in monolayer culture is associated with a decrease in the synthesis of cartilage markers and with a suppressed activation of key signaling proteins in the Ras-mitogen-activated protein kinase pathway (Shc and Erk1/2). These events lead to apoptosis. A decrease in Shc/Erk expression/interaction could serve as a recognition marker for irreversibly dedifferentiated chondrocytes in tissue engineering.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Schulze-Tanzil, G
de Souza, P
John, T
Shakibaei, M
Date : June 2004
DOI : 10.1016/j.joca.2004.02.007
Uncontrolled Keywords : Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Alginates, Apoptosis, Biomarkers, Cartilage, Articular, Caspase 3, Caspases, Cell Differentiation, Cell Division, Cells, Cultured, Chondrocytes, Collagen Type II, Extracellular Matrix, Glucuronic Acid, Hexuronic Acids, Humans, Immunoenzyme Techniques, Integrins, Middle Aged, Mitogen-Activated Protein Kinases, Phosphorylation, Shc Signaling Adaptor Proteins, Signal Transduction, Tyrosine
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:16
Last Modified : 24 Jan 2020 18:53

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