Jianyao Wu, Sofia Movérare-Skrtic, Fu-Ping Zhang, Antti Koskela, Juha Tuukkanen, Jorma J. Palvimo, Petra Sipilä, Matti Poutanen, Claes Ohlsson, Androgen receptor SUMOylation regulates bone mass in male mice, Molecular and Cellular Endocrinology, Volume 479, 2019, Pages 117-122, ISSN 0303-7207, https://doi.org/10.1016/j.mce.2018.09.008
Androgen receptor SUMOylation regulates bone mass in male mice
|Author:||Wu, Jianyao1; Movérare-Skrtic, Sofia1; Zhang, Fu-Ping2;|
1Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland
3Department of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland
4Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
|Online Access:||PDF Full Text (PDF, 0.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019071022981
|Publish Date:|| 2019-07-10
The crucial effects of androgens on the male skeleton are at least partly mediated via the androgen receptor (AR). In addition to hormone binding, the AR activity is regulated by post-translational modifications, including SUMOylation. SUMOylation is a reversible modification in which Small Ubiquitin-related MOdifier proteins (SUMOs) are attached to the AR and thereby regulate the activity of the AR and change its interactions with other proteins.
To elucidate the importance of SUMOylation of AR for male bone metabolism, we used a mouse model devoid of the two AR SUMOylation sites (ARSUM−; K381R and K500R are substituted). Six-month-old male ARSUM− mice displayed significantly reduced trabecular bone volume fraction in the distal metaphyseal region of femur compared with wild type (WT) mice (BV/TV, −19.1 ± 4.9%, P < 0.05). The number of osteoblasts per bone perimeter was substantially reduced (−60.5 ± 7.2%, P < 0.001) while no significant effect was observed on the number of osteoclasts in the trabecular bone of male ARSUM− mice. Dynamic histomorphometric analysis of trabecular bone revealed a reduced bone formation rate (−32.6 ± 7.4%, P < 0.05) as a result of reduced mineralizing surface per bone surface in ARSUM− mice compared with WT mice (−24.3 ± 3.6%, P < 0.001). Furthermore, cortical bone thickness in the diaphyseal region of femur was reduced in male ARSUM− mice compared with WT mice (−7.3 ± 2.0%, P < 0.05).
In conclusion, mice devoid of AR SUMOylation have reduced trabecular bone mass as a result of reduced bone formation. We propose that therapies enhancing AR SUMOylation might result in bone-specific anabolic effects with minimal adverse effects in other tissues.
Molecular and cellular endocrinology
|Pages:||117 - 122|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This study is supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant from the Sahlgrenska University Hospital, the Lundberg Foundation, the European Calcified Tissue Society, the Torsten and Ragnar Söderberg's Foundation, Knut and Alice Wallenberg Foundation, the Academy of Finland and the Novo Nordisk Foundation.
© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).