Scholarlink

<p>Further study of the mechanism of glucocorticoid (GC)-induced osteoblast (OB) apoptosis is highly important for the prevention and treatment of GC-induced osteoporosis and osteonecrosis. Serine/arginine-rich splicing factor 1 (<i>Srsf1</i>) expression was downregulated in a dose-dependent manner during GC-induced OB apoptosis. Knockdown of <i>Srsf1</i> significantly promotes GC-induced OB apoptosis, while overexpression of <i>Srsf1</i> significantly inhibits GC-induced OB apoptosis. Mechanistically, GC induces the up-regulation of histone deacetylase 4 (<i>Hdac4</i>) in OB, and inhibits the expression of transcription activator forkhead box C1 (<i>Foxc1</i>) by reducing the levels of histone H3 lysine 9 acetylation (H3K9ac) and H3K27ac in the promoter region of <i>Foxc1</i>, thereby down-regulating <i>Srsf1</i>. Next, SRSF1 regulates GC-induced OB apoptosis by regulating Bcl-2 modifying factor (<i>Bmf</i>) alternative splicing. From the perspective of alternative splicing, this study demonstrates that <i>Srsf1</i> and its regulatory mechanism may serve as a new target for the prevention and treatment of GC-induced osteoporosis and osteonecrosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Glucocorticoids regulate the expression of Srsf1 through Hdac4/Foxc1 axis to induce apoptosis of osteoblasts

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月4日

查看全文
  • Hong Luo,
  • Tao Wang,
  • Zhihong Xie,
  • Fanchao Li,
  • Chengyou Yang,
  • Wentao Dong,
  • Jianhua Wu,
  • Qiang Wang,
  • Fengyang Xu,
  • Jiong Liu,
  • Fei Zhang,
  • Wuxun Peng

摘要

Further study of the mechanism of glucocorticoid (GC)-induced osteoblast (OB) apoptosis is highly important for the prevention and treatment of GC-induced osteoporosis and osteonecrosis. Serine/arginine-rich splicing factor 1 (Srsf1) expression was downregulated in a dose-dependent manner during GC-induced OB apoptosis. Knockdown of Srsf1 significantly promotes GC-induced OB apoptosis, while overexpression of Srsf1 significantly inhibits GC-induced OB apoptosis. Mechanistically, GC induces the up-regulation of histone deacetylase 4 (Hdac4) in OB, and inhibits the expression of transcription activator forkhead box C1 (Foxc1) by reducing the levels of histone H3 lysine 9 acetylation (H3K9ac) and H3K27ac in the promoter region of Foxc1, thereby down-regulating Srsf1. Next, SRSF1 regulates GC-induced OB apoptosis by regulating Bcl-2 modifying factor (Bmf) alternative splicing. From the perspective of alternative splicing, this study demonstrates that Srsf1 and its regulatory mechanism may serve as a new target for the prevention and treatment of GC-induced osteoporosis and osteonecrosis.