Mechanical strain and estrogen activate estrogen receptor alpha in bone cells.
Jessop, H. L. and Sjöberg, M. and Cheng, Ming Zhao and Zaman, Gul and Wheeler-Jones, C. P. and Lanyon, Lance E. (2001) Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. Journal of Bone and Mineral Research, 16 (6). pp. 1045-1055. ISSN 0884-0431
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Bone cells' early responses to estrogen and mechanical strain were investigated in the ROS 17/2.8 cell line. Immunoblotting with antiphosphorylated estrogen receptor a (ER-alpha) antibody showed that when these cells were exposed for 10 minutes to estrogen (10(-8) M) or a single period of cyclic dynamic strain (peak 3400 microepsilon, 1 Hz, 600 cycles), there was an increase in the intensity of a 66-kDa band, indicating phosphorylation of ser122 in the amino terminus of ER-alpha. Increased phosphorylation was detected within 5 minutes of exposure to estrogen and 5 minutes after the end of the period of strain. Estrogen and strain also activated the mitogen-activated protein kinase (MAPK) family member extracellular regulated kinase-1 (ERK-1). Increases in ERK activation coincided with increased ER-alpha phosphorylation. Activation of ERK-1 and the phosphorylation of ER-alpha, by both estrogen and strain, were prevented by the MAP kinase kinase (MEK) inhibitor U0126 and the protein kinase A (PKA) inhibitor (PKI). These data support previous suggestions that resident bone cells' early responses to strain and estrogen share a common pathway, which involves ER-alpha. This pathway also appears to involve PKA and ERK-mediated phosphorylation of ser122 within the amino terminus of ER-alpha. Reduced availability of this pathway when estrogen levels are reduced could explain diminished effectiveness of mechanically related control of bone architecture after the menopause.
|Research Areas:||A. Middlesex University Schools and Centres > School of Health and Education > Mental Health, Social Work and Interprofessional Learning|
|Citations on ISI Web of Science:||58|
|Deposited On:||22 Feb 2010 16:16|
|Last Modified:||10 Dec 2014 19:27|
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