Crosstalk with bone marrow adipocytes, but not osteoblasts, drives a cortical bone resorption phenotype in female mice with adult-onset deletion of the glucocorticoid receptor in Osterix-expressing cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stem cells (MSCs) and heterogeneous bone marrow stromal cells (BMSCs) are multipotent progenitors that can differentiate into osteoblasts and bone marrow adipocytes (BMAd). The role of BMAd in skeletal homeostasis is not yet fully understood, in part due to a lack of reproducible in vitro models that faithfully mimic the biology and molecular signatures of BMAds to study their behavior. Here, we report the in vitro generation of murine BMSC- and MSC-derived Osterix-expressing BMAd-like cells via a trans-differentiation model (TD-BMAd), the development of a semi-automated analysis platform for quantification of lipid-laden cells, and the use of these models to interrogate the role of the glucocorticoid receptor (GR) in bone marrow adipose tissue (BMAT) as a regulator of osteoclastic bone resorption. The TD-BMAd cells stored intracellular lipids and robustly expressed BMAd-associated genes, such as Sp7 /Osx, Pparg , and Adipoq . The pro-osteoclastogenic gene Tnfsf11 /Rankl was comparably expressed between TD-BMAd and osteoblasts. We previously reported that female mice with adult-onset conditional KO (CKO) of the GR in Osx-expressing cells exhibited a low cortical bone mass and high BMAT phenotype. Here, we demonstrate that this phenotype was associated with an increase in the abundance of cortical bone osteoclasts in female but not male GR-CKO mice, but that surprisi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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