title: Estrogen receptors' roles in the control of mechanically adaptive bone (re)modeling.
abstract: The discovery that estrogen receptors (ERs) are involved in bone cells' responses to mechanical strain offered the prospect of establishing the link between declining levels of circulating estrogen and the progressive failure of the mechanically adaptive mechanisms that should maintain structurally appropriate levels of bone mass in age-related and post-menopausal osteoporosis. Such clarification remains elusive but studies have confirmed ligand-independent involvement of ERs as facilitators in a number of the pathways by which mechanical strain stimulates osteoblast proliferation and bone formation. The presence of α and β forms of ER that oppose, supplement or replace one another has complicated interpretation of studies to identify their individual roles when both are present in normal amounts. However, it appears that, in mice at least, ERα promotes cortical bone mass in both males and females through its effects in early members of the osteoblast lineage, but enhances loading-related cortical bone gain only in females. In addition to its role as a potential replacement for ERα, and modifier of ERα activity, the less well-studied ERβ appears to facilitate rapid early effects of strain including activation of extracellular signal-regulated kinase and downregulation of Sost in well-differentiated cells of the osteoblast lineage including osteocytes. If these different roles are substantiated by further studies, it would appear that under normal circumstances ERα contributes primarily to the size and extent of bones' osteogenic response to load bearing through facilitating anabolic influences in osteoblasts and osteoblast progenitors, whereas ERβ is more involved in the strain-related responses generated within resident cells including osteocytes.
authors.affiliation: School of Veterinary Sciences, University of Bristol , Bristol, UK.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Galea
authors.affiliation: School of Veterinary Sciences, University of Bristol , Bristol, UK.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Price
authors.affiliation: School of Veterinary Sciences, University of Bristol , Bristol, UK.
authors.forename: Lance E
authors.initials: LE
authors.lastname: Lanyon