Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells.
Mechanical input is known to regulate skeletal mass. In vitro, application of strain inhibits osteoclast formation by decreasing expression of the ligand RANKL in bone stromal cells, but the mechanism responsible for this down-regulation is unknown. In experiments here, application of 1.8% equibiaxial strain for 6 h reduced vitamin D-stimulated RANKL mRNA expression by nearly one-half in primary bone stromal cells. Application of strain caused a rapid activation of ERK1/2, which returned to baseline by 60 minutes. Adding the ERK1/2 inhibitor PD98059 30 minutes before strain delivery prevented the strain effect on RANKL mRNA expression, suggesting that activation of ERK1/2 was required for transduction of the mechanical force. Mechanical strain also activated N-terminal Jun kinase (JNK) that, in contrast, did not return to baseline during 24 h of continuous strain. This suggests that JNK may represent an accessory pathway for mechanical transduction in bone cells. Our data indicate that strain modulation of RANKL expression involves activation of MAPK pathways.
Rubin
Janet
J
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Murphy
Tamara C
TC
Fan
Xian
X
Goldschmidt
Mark
M
Taylor
W Robert
WR
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001842:Bone and Bones / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one