Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1452-1460 |
| Number of pages | 9 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 17 |
| Issue number | 8 |
| DOIs | |
| State | Published - Jan 1 2002 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine
Cite this
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Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells. / Rubin, Janet; Murphy, Tamara C.; Fan, Xian; Goldschmidt, Marc; Taylor, W. Robert.
In: Journal of Bone and Mineral Research, Vol. 17, No. 8, 01.01.2002, p. 1452-1460.Research output: Contribution to journal › Article
TY - JOUR
T1 - Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells
AU - Rubin, Janet
AU - Murphy, Tamara C.
AU - Fan, Xian
AU - Goldschmidt, Marc
AU - Taylor, W. Robert
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035992651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035992651&partnerID=8YFLogxK
U2 - 10.1359/jbmr.2002.17.8.1452
DO - 10.1359/jbmr.2002.17.8.1452
M3 - Article
C2 - 12162499
AN - SCOPUS:0035992651
VL - 17
SP - 1452
EP - 1460
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 8
ER -