Inhibition of cell-matrix adhesions prevents cartilage chondrocyte death following impact injury.
Inhibition of cell-matrix adhesions prevents cartilage chondrocyte death following impact injury.
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DOI：
10.1002/jor.22523
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发表时间：
2014-03
影响因子：
2.8
通讯作者：
Martin, James A.
中科院分区：
文献类型：
--
作者：
Jang, Kee W.;Buckwalter, Joseph A.;Martin, James A.
Focal adhesions are transmembrane protein complexes that attach chondrocytes to the pericellular cartilage matrix and in turn, are linked to intracellular organelles via cytoskeleton. We previously found that excessive compression of articular cartilage leads to cytoskeleton-dependent chondrocyte death. Here we tested the hypothesis that this process also requires integrin activation and signaling via focal adhesion kinase (FAK) and Src family kinase (SFK). Osteochondral explants were treated with FAK and SFK inhibitors (FAKi, SFKi respectively) for 2 hours and then subjected to a death-inducing impact load. Chondrocyte viability was assessed by confocal microscopy immediately and at 24 hours post-impact. With no treatment immediate post-impact viability was 59%. Treatment with 10μM SFKi, 10μM or 100μM FAKi improved viability to 80%, 77%, and 82% respectively (p<0.05). After 24 hours viability declined to 34% in controls, 48% with 10μM SFKi, 45% with 10μM FAKi, and 56% with 100μM FAKi (p<0.01) treatment. These results confirmed that most of the acute chondrocyte mortality was FAK- and SFK-dependent, which implicates integrin-cytoskeleton interactions in the death signaling pathway. Together with previous findings, these data support the hypothesis that the excessive tissue strains accompanying impact loading induce death via a pathway initiated by strain on cell adhesion receptors.
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DOI：
10.1083/jcb.200204153
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Galbraith CG;Yamada KM;Sheetz MP
通讯作者：
Sheetz MP
影响因子：
7.5
作者：
Howe, A;Aplin, AE;Juliano, RL
通讯作者：
Juliano, RL
DOI：
10.1083/jcb.200703036
发表时间：
2007-12-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Humphries JD;Wang P;Streuli C;Geiger B;Humphries MJ;Ballestrem C
通讯作者：
Ballestrem C
影响因子：
56.9
作者：
Amano, M;Chihara, K;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
2.8
作者：
Ikenoue, T;Trindade, MCD;Smith, RL
通讯作者：
Smith, RL