Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss

作者：Wenyu Fu, Meng Chen, Kaidi Wang, Yujianan Chen, Yazhou Cui, Yangli Xie, Zi‐Ning Lei, Wenhuo Hu, Guodong Sun, Guiwu Huang, Chao He, Jackie A. Fretz, Aubryanna Hettinghouse, Ronghan Liu, Xianyi Cai, Mingshuang Zhang, Yuehong Chen, Nan Jiang, Ming He, Daniel H. Wiznia, Huiyun Xu, Zhe‐Sheng Chen, Lin Chen, Kanglai Tang, Hong Zhou, Liu C · 发表于：Cell Research · 年份：2025 · DOI：10.1038/s41422-024-01016-0 · 被引用次数：13 · 研究领域：S100 Proteins and Annexins、Neuropeptides and Animal Physiology、Cytokine Signaling Pathways and Interactions

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.