Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12793
Title: The androgen receptor has no direct antiresorptive actions in mouse osteoclasts.
Authors: Sinnesael, Mieke;Jardi, Ferran;Deboel, Ludo;Laurent, Michaël R;Dubois, Vanessa;Zajac, Jeffrey D;Davey, Rachel A;Carmeliet, Geert;Claessens, Frank;Vanderschueren, Dirk
Affiliation: Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. Electronic address: dirk.vanderschueren@uzleuven.be.
Issue Date: 6-May-2015
Citation: Molecular and Cellular Endocrinology 2015; 411(): 198-206
Abstract: Androgen deficiency or androgen receptor knockout (ARKO) causes high-turnover osteopenia, but the target cells for this effect remain unclear. To examine whether AR in osteoclasts directly suppresses bone resorption, we crossed AR-floxed with cathepsin K-Cre mice. Osteoclast-specific ARKO (ocl-ARKO) mice showed no changes neither in osteoclast surface nor in bone microarchitecture nor in the response to orchidectomy and androgen replacement, indicating that the AR in osteoclasts is not critical for bone maintenance. In line with the lack of a bone phenotype, the levels of AR were very low in osteoclast-enriched cultures derived from bone marrow (BM) and undetectable in osteoclasts generated from spleen precursors. Since tibiae of ubiquitous ARKO mice displayed increased osteoclast counts, the role of AR was further explored using cell cultures from these animals. Osteoclast generation and activity in vitro were similar between ARKO and wildtype control (WT) mice. In co-culture experiments, BM stromal cells (BMSCs) were essential for the suppressive action of AR on osteoclastogenesis and osteoclast activity. Stimulation with 1,25(OH)2 vitamin D3 increased Rankl and decreased Tnfsf11 (osteoprotegerin, Opg) gene expression in BMSCs more than in osteoblasts. This increase in the Rankl/Opg ratio following 1,25(OH)2D3 stimulation was lower, not higher, in ARKO mice. Runx2 expression in BMSCs was however higher in ARKO vs. WT, suggesting that ARKO mice may more readily commit osteoprogenitor cells to osteoblastogenesis. In conclusion, the AR does not seem to suppress bone resorption through direct actions in osteoclasts. BMSCs may however represent an alternative AR target in the BM milieu.
Internal ID Number: 25958043
URI: http://ahro.austin.org.au/austinjspui/handle/1/12793
DOI: 10.1016/j.mce.2015.04.030
URL: http://www.ncbi.nlm.nih.gov/pubmed/25958043
Type: Journal Article
Subjects: Androgen receptor
Androgens
Bone marrow stromal cell
Bone resorption
Osteoblast
Osteoclast
Appears in Collections:Journal articles

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