NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the Modulation of Systemic Bone Turnover

Journal article


Publication Details

Author(s): Scholtysek C, Ipseiz N, Böhm C, Krishnacoumar B, Stenzel M, Czerwinski T, Palumbo-Zerr K, Rothe T, Weidner D, Klej A, Stoll C, Distler J, Tuckermann J, Herrmann M, Fabry B, Goldmann W, Schett G, Krönke G
Journal: Journal of Bone and Mineral Research
Publication year: 2018
ISSN: 0884-0431


Abstract

NR4A1 (Nur77 or NGFI-B), an orphan member of the nuclear receptor superfamily, has been identified as a key regulator of the differentiation and function of myeloid, lymphoid, and mesenchymal cells. The detailed role of NR4A1 in bone biology is incompletely understood. Here, we report a role for NR4A1 as novel factor controlling the migration and recruitment of osteoclast precursors during bone remodeling. Myeloid-specific but not osteoblast-specific deletion of NR4A1 resulted in osteopenia due to an increase in the number of bone-lining osteoclasts. Although NR4A1-deficient osteoclast precursors displayed a regular differentiation into mature osteoclasts, they showed a hyper-motile phenotype that was largely dependent on increased osteopontin expression, suggesting that expression of NR4A1 negatively controlled osteopontin-mediated recruitment of osteoclast precursors to the trabecular bone. Pharmacological activation of NR4A1, in turn, inhibited osteopontin expression and osteopontin-dependent migration of osteoclast precursors resulted in reduced abundance of bone-resorbing osteoclasts in vivo as well as in an ameliorated bone loss after ovariectomy in mice. This study identifies NR4A1 as a crucial player in the regulation of osteoclast biology and bone remodeling and highlights this nuclear receptor as a promising target for therapeutic intervention during the treatment of osteoporosis. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.


FAU Authors / FAU Editors

Czerwinski, Tina
Lehrstuhl für Biophysik
Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose
Fabry, Ben Prof. Dr.
Lehrstuhl für Biophysik
Goldmann, Wolfgang Prof.
Lehrstuhl für Biophysik
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Krönke, Gerhard Prof. Dr. med.
Professur für Translationale Immunologie
Rothe, Tobias Dr. rer. nat.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Stenzel, Martin
Medizinische Klinik 3 - Rheumatologie und Immunologie


External institutions with authors

Cardiff University
Universität Ulm


How to cite

APA:
Scholtysek, C., Ipseiz, N., Böhm, C., Krishnacoumar, B., Stenzel, M., Czerwinski, T.,... Krönke, G. (2018). NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the Modulation of Systemic Bone Turnover. Journal of Bone and Mineral Research. https://dx.doi.org/10.1002/jbmr.3533

MLA:
Scholtysek, Carina, et al. "NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the Modulation of Systemic Bone Turnover." Journal of Bone and Mineral Research (2018).

BibTeX: 

Last updated on 2019-18-07 at 07:36