Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss Journal Article
| Authors: | Fu, W.; Chen, M.; Wang, K.; Chen, Y.; Cui, Y.; Xie, Y.; Lei, Z. N.; Hu, W.; Sun, G.; Huang, G.; He, C.; Fretz, J.; Hettinghouse, A.; Liu, R.; Cai, X.; Zhang, M.; Chen, Y.; Jiang, N.; He, M.; Wiznia, D. H.; Xu, H.; Chen, Z. S.; Chen, L.; Tang, K.; Zhou, H.; Liu, C. J. |
| Article Title: | Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss |
| Abstract: | Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis. © The Author(s) 2024. |
| Keywords: | controlled study; osteolysis; drug megadose; animal experiment; animal model; dexamethasone; food and drug administration; glucocorticoid; rheumatoid arthritis; osteoporosis; drug therapy; adverse drug reaction; therapy; human; male; article; hydromethylthionine |
| Journal Title: | Cell Research |
| Volume: | 35 |
| Issue: | 1 |
| ISSN: | 1001-0602 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-01-01 |
| Start Page: | 23 |
| End Page: | 44 |
| Language: | English |
| DOI: | 10.1038/s41422-024-01016-0 |
| PUBMED: | 39743632 |
| PROVIDER: | scopus |
| PMCID: | PMC11701132 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
