Estrogen Receptor-alpha Is Required for the Osteogenic Response to Mechanical Loading in a Ligand-Independent Manner Involving Its Activation Function 1 but Not 2

Windahl, S H; Saxon, L K; Borjesson, A E; Lagerquist, M K; Frenkel, B; Henning, P; Lerner, U H; Galea, G L; Meakin, L B; Engdahl, C; Sjogren, K; Antal, M C; Krust, A; Chambon, P; Lanyon, L E; Price, J S; Ohlsson, C

Abstract

Estrogen receptor‐α (ERα) is crucial for the adaptive response of bone to loading but the role of endogenous estradiol (E2) for this response is unclear. To determine in vivo the ligand dependency and relative roles of different ERα domains for the osteogenic response to mechanical loading, gene‐targeted mouse models with (1) a complete ERα inactivation (ERα−/−), (2) specific inactivation of activation function 1 (AF‐1) in ERα (ERαAF‐10), or (3) specific inactivation of ERαAF‐2 (ERαAF‐20) were subjected to axial loading of tibia, in the presence or absence (ovariectomy [ovx]) of endogenous E2. Loading increased the cortical bone area in the tibia mainly as a result of an increased periosteal bone formation rate (BFR) and this osteogenic response was similar in gonadal intact and ovx mice, demonstrating that E2 (ligand) is not required for this response. Female ERα−/− mice displayed a severely reduced osteogenic response to loading with changes in cortical area (−78% ± 15%, p 

Citation

Windahl, S. H., Saxon, L. K., Borjesson, A. E., Lagerquist, M. K., Frenkel, B., Henning, P., …Ohlsson, C. (2013). Estrogen Receptor-alpha Is Required for the Osteogenic Response to Mechanical Loading in a Ligand-Independent Manner Involving Its Activation Function 1 but Not 2. Journal of Bone and Mineral Research, 28(2), 291-301. https://doi.org/10.1002/jbmr.1754

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2012
• Publication Date: Jan 15, 2013
• Deposit Date: Nov 12, 2014
• Journal: JOURNAL OF BONE AND MINERAL RESEARCH
• Print ISSN: 0884-0431
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 2
• Pages: 291-301
• DOI: https://doi.org/10.1002/jbmr.1754
• Public URL: https://rvc-repository.worktribe.com/output/1409363
• Additional Information: Corporate Creators : Bristol, Gothenburg, Inserm, Paris, Southern California, LA, Umea University Hospital, Sweden