title: Mechanical strain and estrogen activate estrogen receptor alpha in bone cells.
abstract: 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.
authors.affiliation: Department of Veterinary Basic Sciences, The Royal Veterinary College, London, United Kingdom.
authors.forename: H L
authors.initials: HL
authors.lastname: Jessop
authors.forename: M
authors.initials: M
authors.lastname: Sjöberg
authors.forename: M Z
authors.initials: MZ
authors.lastname: Cheng
authors.forename: G
authors.initials: G
authors.lastname: Zaman
authors.forename: C P
authors.initials: CP
authors.lastname: Wheeler-Jones
authors.forename: L E
authors.initials: LE
authors.lastname: Lanyon
mesh_terms: D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D002070:Butadienes; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D009570:Nitriles; D011960:Receptors, Estrogen; C113580:U 0126; C015482:protein kinase modulator; D012694:Serine; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases