美国耶鲁大学Chuan-Ju Liu团队发现，Tau是一种对糖皮质激素亲和力较低的受体，并且在糖皮质激素引起的骨丧失过程中是必需的。2025年1月2日，国际知名学术期刊《细胞研究》在线发表了这一成果。

研究人员发现Tau是一个低亲和力的糖皮质激素（GC）结合受体，在GC引起的骨丧失中起着关键作用。无论是在炎症性关节炎还是GC引起的骨质疏松（GIO）模型中，Tau缺乏显著消除了高剂量地塞米松（一种合成GC）引起的骨丧失。

此外，从FDA批准的药物库中识别出的Tau抑制剂TRx0237有效防止了GIO。值得注意的是，TRx0237与地塞米松联合使用完全克服了地塞米松在治疗炎症性关节炎中的骨质疏松副作用。

这些发现将Tau呈现为一个以前未被识别的低亲和力GC受体，并提供了缓解GC相关副作用，特别是骨质疏松的潜在策略。

据介绍，GC是最常用的抗炎和免疫抑制药物。然而，由于其显著的副作用，使用往往受到限制，例如GIO，其潜在机制仍未完全了解。

附：英文原文

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

Author: Fu, Wenyu, Chen, Meng, Wang, Kaidi, Chen, Yujianan, Cui, Yazhou, Xie, Yangli, Lei, Zi-Ning, Hu, Wenhuo, Sun, Guodong, Huang, Guiwu, He, Chaopeng, Fretz, Jackie, Hettinghouse, Aubryanna, Liu, Ronghan, Cai, Xianyi, Zhang, Mingshuang, Chen, Yuehong, Jiang, Nan, He, Minchun, Wiznia, Daniel H., Xu, Huiyun, Chen, Zhe-Sheng, Chen, Lin, Tang, Kanglai, Zhou, Hong, Liu, Chuan-Ju

Issue&Volume: 2025-01-02

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.

DOI: 10.1038/s41422-024-01016-0

Source: https://www.nature.com/articles/s41422-024-01016-0