AUTHOR=Schill Rebecca L. , Visser Jack , Ashby Mariah L. , Li Ziru , Lewis Kenneth T. , Morales-Hernandez Antonio , Hoose Keegan S. , Maung Jessica N. , Uranga Romina M. , Hariri Hadla , Hermsmeyer Isabel D. K. , Mori Hiroyuki , MacDougald Ormond A. 

TITLE=Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1397081

DOI=10.3389/fendo.2024.1397081

ISSN=1664-2392

ABSTRACT=Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. In this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots. Mice lacking GR in BMAds (BMAd-Nr3c1 -/-) and control mice (BMAd-Nr3c1 +/+ ) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1 -/-mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1 -/-mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and µCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1 -/-mice. Differences in BMAd size were not observed between BMAd-Nr3c1 -/-and control mice. Interestingly, BMAd-Nr3c1 - /-mice had decreased circulating white blood cell counts 4 h into the light cycle. In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions RLS, JV, MLA, ZL and OAM conceived the studies and planned the experimental design. RLS, JV, MLA, ZL, KTL, AMH, KSH, JNM, RMU, HH, IDKH, and HM, performed the experiments. RLS and OAM analyzed the data. RLS and OAM wrote the manuscript, while all other authors edited and approved the final manuscript.