MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells.
The activating protein-1 (AP-1) complex plays a critical role in bone physiology, including its response to strain. We studied gene expression and nuclear translocation kinetics of the seven AP-1 members, after substrate deformation (Flexcell) or simulated microgravity (Clinostat), in osteoblastic ROS17/2.8 cells. Gene expression and nuclear translocation of all the AP-1 members were induced, under both conditions, with differences in their kinetics, except fosB mRNA in the Clinostat. Downregulation of protein kinase C (PKC) and COX1/2 or inhibition of ERK1/2, p38(MAPK) or src kinases had no major effect on AP-1 mRNA expression in the Flexcell. In contrast, ERK1/2, p38(MAPK) and src kinases treatment blocked nuclear translocation of almost all the AP-1 members in both models, except Fra-1, JunD after deformation and Fra-1, JunB after clinorotation. Thus, changes in the osteoblastic mechanical environment induced a dramatic induction of most of the AP-1 members with specific kinetics and involved MAPK and src kinase pathways, which differed whether the cells were stretched or clinorotated.
Granet
Corinne
C
Laboratoire de Biologie et de Biochimie du Tissu Osseux LBBTO-INSERM E9901, Faculté de Médecine, 15 rue A. Paré, 42023 Saint-Etienne Cedex 2, France.
Vico
Alain Guignandon Laurence
AG
Alexandre
Christian
C
Lafage-Proust
Marie-Hélène
MH
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051921:Fos-Related Antigen-2; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010006:Osteoblasts / Q000201:enzymology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018474:Weightlessness Simulation; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099169:Fos-Related Antigen 1
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D051921:Fos-Related Antigen-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases; D000099169:Fos-Related Antigen 1; C483820:Fosb protein, rat