Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage
AuthorsFanning, Paul J.
Smith, Robert J.
Grodzinsky, Alan J.
Trippel, Stephen B.
UMass Chan AffiliationsDepartment of Orthopedics and Physical Rehabilitation
Document TypeJournal Article
Insulin-Like Growth Factor I
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Rehabilitation and Therapy
MetadataShow full item record
AbstractArticular chondrocytes respond to mechanical forces by alterations in gene expression, proliferative status, and metabolic functions. Little is known concerning the cell signaling systems that receive, transduce, and convey mechanical information to the chondrocyte interior. Here, we show that ex vivo cartilage compression stimulates the phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK1) of the JNK pathway. Mechanical compression induced a phased phosphorylation of ERK consisting of a rapid induction of ERK1/2 phosphorylation at 10 min, a rapid decay, and a sustained level of ERK2 phosphorylation that persisted for at least 24 h. Mechanical compression also induced the phosphorylation of p38 MAPK in strictly a transient fashion, with maximal phosphorylation occurring at 10 min. Mechanical compression stimulated SEK1 phosphorylation, with a maximum at the relatively delayed time point of 1 h and with a higher amplitude than ERK1/2 and p38 MAPK phosphorylation. These data demonstrate that mechanical compression alone activates MAPK signaling in intact cartilage. In addition, these data demonstrate distinct temporal patterns of MAPK signaling in response to mechanical loading and to the anabolic insulin-like growth factor-I. Finally, the data indicate that compression coactivates distinct signaling pathways that may help define the nature of mechanotransduction in cartilage.
SourceJ Biol Chem. 2003 Dec 19;278(51):50940-8. Epub 2003 Sep 2. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43069
Related ResourcesLink to Article in PubMed
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A mammalian scaffold complex that selectively mediates MAP kinase activationWhitmarsh, Alan J.; Cavanagh, Julie; Tournier, Cathy; Yasuda, Jun; Davis, Roger J. (1998-09-11)The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by the exposure of cells to multiple forms of stress. A putative scaffold protein was identified that interacts with multiple components of the JNK signaling pathway, including the mixed-lineage group of MAP kinase kinase kinases (MLK), the MAP kinase kinase MKK7, and the MAP kinase JNK. This scaffold protein selectively enhanced JNK activation by the MLK signaling pathway. These data establish that a mammalian scaffold protein can mediate activation of a MAP kinase signaling pathway.
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