Role of Dkk2 in the Muscle/bone Interaction of Androgen-Deficient Mice
- 22 December 2020
- journal article
- research article
- Published by Georg Thieme Verlag KG in Experimental and Clinical Endocrinology & Diabetes
- Vol. 129 (10), 770-775
- https://doi.org/10.1055/a-1331-7021
Abstract
Androgen deficiency is known to cause both osteoporosis and sarcopenia. Myokines, humoral factors secreted from the skeletal muscles, have recently been getting attention as the key factors related to the interactions between muscle and bone. Dickkopf (Dkk) 2 is known as an inhibitor of canonical Wnt/β-catenin signaling, and Wnt/β-catenin signaling is crucial for the maintenance of muscle and bone. The present study was therefore performed to investigate the roles of Dkk2 in the alterations of muscle and bone of androgen-deficient mice with orchidectomy (ORX). ORX significantly enhanced Dkk2 mRNA levels, but not other Dkks and secreted frizzled related proteins, in the soleus muscles of mice. Moreover, ORX enhanced serum Dkk2 levels, but not Dkk2 mRNA levels in the tibial bone tissues, the white adipose tissues and liver of mice. In simple regression analyses, serum Dkk2 levels were negatively related to trabecular bone mineral density at the tibias in mice employed in the experiments. In vitro experiments, testosterone suppressed Dkk2 mRNA levels in mouse muscle C2C12 cells. In conclusion, we showed that androgen deficiency enhances Dkk2 expression and secretion in the muscles of mice. Dkk2 might be involved in androgen deficiency-induced muscle wasting and osteopenia as a myokine linking muscle to bone. Received: 22 July 2020 Received: 27 November 2020 Accepted: 07 December 2020 Publication Date: 22 December 2020 (online) © 2020. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyKeywords
This publication has 28 references indexed in Scilit:
- Role of irisin in androgen-deficient muscle wasting and osteopenia in miceJournal of Bone and Mineral Metabolism, 2019
- Muscular responses to testosterone replacement vary by administration route: a systematic review and meta‐analysisJournal of Cachexia, Sarcopenia and Muscle, 2018
- Estrogens and Androgens in Skeletal Physiology and PathophysiologyPhysiological Reviews, 2017
- Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and diseaseBone, 2015
- Interactions Between Muscle Tissues and Bone MetabolismJournal of Cellular Biochemistry, 2014
- Androgen Receptor Action in Osteoblasts in Male Mice Is Dependent on Their Stage of MaturationJournal of Bone and Mineral Research, 2014
- Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytesJournal of Bone and Mineral Research, 2012
- Osteoporosis in Men: An Endocrine Society Clinical Practice GuidelineJournal of Clinical Endocrinology & Metabolism, 2012
- Update in Male OsteoporosisJournal of Clinical Endocrinology & Metabolism, 2010
- Risk of Fracture after Androgen Deprivation for Prostate CancerThe New England Journal of Medicine, 2005