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Activation of Extracellular Signal–Regulated Kinase Is Involved in Mechanical Strain Inhibition of RANKL Expression in Bone Stromal Cells
Author(s) -
Rubin Janet,
Murphy Tamara C.,
Fan Xian,
Goldschmidt Mark,
Taylor W. Robert
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.8.1452
Subject(s) - rankl , stromal cell , mapk/erk pathway , microbiology and biotechnology , signal transduction , osteoclast , kinase , chemistry , strain (injury) , extracellular , in vitro , medicine , biology , cancer research , receptor , biochemistry , activator (genetics)
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.