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• W1966013695 abstract "To define the role of mitogen activated protein (MAP) kinases in fibronectin fragment (Fn-f) mediated matrix metalloproteinase (MMP) upregulation and damage to bovine cartilage and to compare activities of three Fn-fs with native fibronectin (Fn), which is inactive in terms of cartilage damage.Bovine chondrocytes were cultured with three Fn-fs, an amino-terminal 29-kDa, a gelatin-binding 50-kDa and a central 140-kDa Fn-f or native Fn at concentrations from 0.01 to 1 microM, concentrations lower than those found in osteoarthritis synovial fluids. Lysates were probed for activation of MAP kinases, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and stress activated protein kinase/c-jun N-terminal kinase (SAPK/JNK). Confocal fluorescent microscopy was used to visualize movement of activated kinases. Kinase inhibitors were tested for their abilities to block Fn-f mediated protein upregulation of MMP-3 and MMP-13 and Fn-f induced depletion of cartilage proteoglycan (PG) from cultured explants.The 29-kDa, the most potent Fn-f in terms of cartilage damage, enhanced phosphorylation of ERK1/2, p38 and JNK1/2 within a 1-h incubation while the 50 and 140-kDa Fn-fs required up to 4 h for maximal activity and native Fn was only minimally active toward p38 and JNK, but did strongly activate ERK1/2. The activated kinases displayed a distribution toward the nuclear membrane and within the nucleus. MAP kinase inhibitors markedly decreased Fn-f mediated upregulation of MMP-3 or MMP-13 and Fn-f mediated cartilage PG depletion.These results suggest that Fn-fs upregulate MMP-3 and MMP-13 in bovine chondrocytes through MAP kinases and that kinase inhibitors afford protection against this degenerative pathway." @default.
• W1966013695 created "2016-06-24" @default.
• W1966013695 creator A5012931115 @default.
• W1966013695 creator A5035440542 @default.
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• W1966013695 date "2008-10-01" @default.
• W1966013695 modified "2023-10-11" @default.
• W1966013695 title "The cartilage chondrolytic mechanism of fibronectin fragments involves MAP kinases: comparison of three fragments and native fibronectin" @default.
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• W1966013695 doi "https://doi.org/10.1016/j.joca.2008.02.015" @default.
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