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Mechanical Strain and Estrogen Activate Estrogen Receptor α in Bone Cells
Author(s) -
Jessop H. L.,
Sjöberg M.,
Cheng M. Z.,
Zaman G.,
WheelerJones C. P. D.,
Lanyon L. E.
Publication year - 2001
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.2001.16.6.1045
Subject(s) - estrogen , mapk/erk pathway , protein kinase a , phosphorylation , estrogen receptor , estrogen receptor alpha , kinase , endocrinology , medicine , mek inhibitor , chemistry , estrogen receptor beta , biology , microbiology and biotechnology , cancer , breast cancer
Bone cells' early responses to estrogen and mechanical strain were investigated in the ROS 17/2.8 cell line. Immunoblotting with antiphosphorylated estrogen receptor α (ER‐α) 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 μϵ, 1Hz, 600 cycles), there was an increase in the intensity of a 66‐kDa band, indicating phosphorylation of ser 122 in the amino terminus of ER‐α. 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‐α phosphorylation. Activation of ERK‐1 and the phosphorylation of ER‐α, 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‐α. This pathway also appears to involve PKA and ERK‐mediated phosphorylation of ser 122 within the amino terminus of ER‐α. Reduced availability of this pathway when estrogen levels are reduced could explain diminished effectiveness of mechanically related control of bone architecture after the menopause.