| First Author | Scholtysek C | Year | 2018 |
| Journal | J Bone Miner Res | Volume | 33 |
| Issue | 11 | Pages | 2035-2047 |
| PubMed ID | 29949664 | Mgi Jnum | J:359760 |
| Mgi Id | MGI:6831914 | Doi | 10.1002/jbmr.3533 |
| Citation | Scholtysek C, et al. (2018) NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the Modulation of Systemic Bone Turnover. J Bone Miner Res 33(11):2035-2047 |
| abstractText | 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. (c) 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. |
