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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月2日

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

摘要

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.