Glucocorticoid receptor regulates osteoblast differentiation in association with Map7d2 and Erk2 signaling
4 affiliations
- 1Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center
- 2Institute of Molecular Endocrinology and Physiology, Ulm University
- 3Integrated 3R Center Ulm (i3RU), Ulm University
- 4German Center for Child and Adolescent Health (DZKJ), partner site Ulm
Abstract
The glucocorticoid receptor (GR) is an important regulator of skeletal homeostasis; however, the molecular mechanisms through which it regulates osteogenic differentiation remain incompletely understood. Here, we investigated the role of GR using two complementary primary murine osteogenic cell models, bone marrow stromal cells (BMSCs) and bone-derived primary osteoblasts, together with comparative transcriptomic analyses. GR depletion significantly impaired osteogenic differentiation in both cell preparations, as demonstrated by reduced alkaline phosphatase (Alp) activity and altered expression of osteogenic markers. RNA sequencing (RNA-seq) revealed extensive transcriptional changes following GR knockdown, with 3,530 differentially expressed genes (DEGs) in BMSCs and 4,657 in primary osteoblasts. Despite substantial differences in gene expression profiles of the two osteogenic cell models, pathway enrichment analyses revealed common biological processes, including MAPK signaling and cell migration. Comparative transcriptomic analysis further identified only 17 genes that were consistently regulated in the same direction in both cell preparations, among which Map7d2 emerged as a previously unrecognized GR-responsive candidate. Combined depletion of GR and Map7d2 partially restored cellular Alp activity and the expression of selected osteogenic markers compared with GR depletion alone. Western blot analysis further showed restoration of Erk2 phosphorylation and Alp protein expression following combined GR and Map7d2 depletion, demonstrating an association between the partial rescue of selected osteogenic readouts and restoration of Erk2 signaling. Together, these findings identify Map7d2 as a previously unrecognized GR-responsive candidate associated with Erk2 signaling and osteogenic differentiation. Our study reveals common molecular responses to GR depletion across two primary murine osteogenic cell models and provides new insights into the transcriptional and signaling networks underlying GR-regulated osteogenic differentiation.
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BibTeX
@article{kolbl2026glucocorticoid,
title = {{Glucocorticoid receptor regulates osteoblast differentiation in association with Map7d2 and Erk2 signaling}},
author = {Christoph Kölbl and Amelie Eckert and Sandra Nungeß and Sooyeon Lee and Jan Tuckermann and Anita Ignatius and Mubashir Ahmad},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1967862},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967862/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glucocorticoid receptor regulates osteoblast differentiation in association with Map7d2 and Erk2 signaling
AU - Christoph Kölbl
AU - Amelie Eckert
AU - Sandra Nungeß
AU - Sooyeon Lee
AU - Jan Tuckermann
AU - Anita Ignatius
AU - Mubashir Ahmad
PY - 2026
DA - 2026/10/29
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1967862
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967862/full
AB - The glucocorticoid receptor (GR) is an important regulator of skeletal homeostasis; however, the molecular mechanisms through which it regulates osteogenic differentiation remain incompletely understood. Here, we investigated the role of GR using two complementary primary murine osteogenic cell models, bone marrow stromal cells (BMSCs) and bone-derived primary osteoblasts, together with comparative transcriptomic analyses. GR depletion significantly impaired osteogenic differentiation in both cell preparations, as demonstrated by reduced alkaline phosphatase (Alp) activity and altered expression of osteogenic markers. RNA sequencing (RNA-seq) revealed extensive transcriptional changes following GR knockdown, with 3,530 differentially expressed genes (DEGs) in BMSCs and 4,657 in primary osteoblasts. Despite substantial differences in gene expression profiles of the two osteogenic cell models, pathway enrichment analyses revealed common biological processes, including MAPK signaling and cell migration. Comparative transcriptomic analysis further identified only 17 genes that were consistently regulated in the same direction in both cell preparations, among which Map7d2 emerged as a previously unrecognized GR-responsive candidate. Combined depletion of GR and Map7d2 partially restored cellular Alp activity and the expression of selected osteogenic markers compared with GR depletion alone. Western blot analysis further showed restoration of Erk2 phosphorylation and Alp protein expression following combined GR and Map7d2 depletion, demonstrating an association between the partial rescue of selected osteogenic readouts and restoration of Erk2 signaling. Together, these findings identify Map7d2 as a previously unrecognized GR-responsive candidate associated with Erk2 signaling and osteogenic differentiation. Our study reveals common molecular responses to GR depletion across two primary murine osteogenic cell models and provides new insights into the transcriptional and signaling networks underlying GR-regulated osteogenic differentiation.
SN - 1664-3224
ER -