Loss of androgen receptor promotes adipogenesis but suppresses osteogenesis in bone marrow stromal cells
Authors: Meng-Yin Tsai
Jie Luo
Hong-Yo Kang
Chawnshang Chang
Kuo-Pao Lai
Yuhchyau Chen
Chiung-Kuei Huang
Soo Ok Lee
Journal: Stem Cell Research (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gender differences; osteoporosis; bone marrow stromal cells; androgen receptor; osteogenesis
Affiliations: George Whipple Lab for Cancer Research, Department of Pathology, and The Wilmot Cancer Center University of Rochester Medical Center, Rochester, NY 14642, USA.

Abstract:  Gender differences have been described in osteoporosis with females having a higher risk of osteoporosis than males. The differentiation of bone marrow stromal cells (BMSCs) into bone or fat is a critical step for osteoporosis. Here we demonstrated that loss of the androgen receptor (AR) in BMSCs suppressed osteogenesis but promoted adipogenesis. The mechanism dissection studies revealed that AR deficiency suppressed osteogenesis-related genes to inhibit osteoblast differentiation from BMSCs. Knockout of AR promoted adipogenesis of BMSCs via Akt activation through IGFBP3-mediated IGF signaling, and the 5' promoter assay and chromatin immunoprecipitation assays further proved that AR could modulate IGFBP3 expression at the transcriptional level. Finally, addition of IGF inhibitors successfully masked the AR deficiency-induced Akt activation, and inhibitions of Akt, IGF1, and IGF2 pathways reversed the AR depletion effects on the adipogenesis process. These results suggested that AR-mediated changes in IGFBP3 might modulate the IGF-Akt axis to regulate adipogenesis in BMSCs. 

Retracted: No

PubPeer comments:
 Figure 3C: The panel representing ARKO mice appears to look similar to a panel in Figure 1E of another paper by the same group where it represents  BM-MSCs (presumed WT, not ARKO mice). Could the authors clarify if these are from the same mouse? The other paper is: Chiung-Kuei Huang et al. Biochimica et Biophysica Acta 1833 (2013) 1222u20131234, DOI: 10.1016 j.bbamcr.2013.01.007 Marked with red boxes. ![file] , 
 Thanks for the comment. We have found the original data and checked the manuscript carefully. During figure preparation, the wrong image highlighted with red color was inadvertently inserted during figure preparation. The corrected image highlighted with green color is shown in the right panel. The authors declare that this correction does not change the original results or conclusions and sincerely apologize for the mistake. ![file] , 
 #2 Dr. Huang: I appreciate you posting the corrected image. Will you be contacting the journal to publish a correction? , 
 Thanks for your reply. Yes, we will contact journal for correction. , 
 #4 Is there an update on this? , 
 #5 The correction has been published in another journal. Thank you. Corrigendum to  Suppression of androgen receptor enhances the self-renewal of mesenchymal stem cells through elevated expression of EGFR [Biochim. Biophys. Acta. 2013 May; 1833 (5): 1222-34]. Huang CK, Tsai MY, Luo J, Kang HY, Lee SO, Chang C. Biochim Biophys Acta Mol Cell Res. 2020 Aug;1867(8):118730. doi: 10.1016 j.bbamcr.2020.118730. Epub 2020 May 11. ,