Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage.
Articular 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.
Fanning
Paul J
PJ
Massachusetts General Hospital, Orthopaedic Research Laboratories, and Harvard Medical School, Boston, Massachusetts, USA. paul.fanning@umassmed.edu
Emkey
Gregory
G
Smith
Robert J
RJ
Grodzinsky
Alan J
AJ
Szasz
Nora
N
Trippel
Stephen B
SB
D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D007334:Insulin-Like Growth Factor I; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases