Scholarlink

<p>Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation, apoptosis, and differentiation, with the Wnt/β-catenin signaling pathway playing a pivotal role. However, the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear. Smad7, a key antagonist of the TGF-β superfamily, is essential for maintaining tissue homeostasis and ensuring proper cellular function. Our previous study has demonstrated that <i>Smad7</i> knockout in mice leads to impaired proliferative property of tooth germ cells, resulting in small molars. Here, we identified SMAD7 expression in human dental papilla and dental pulp, colocalized with β-CATENIN and cell proliferation-related proteins. RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in <i>Smad7</i>-deficient mouse tooth germs. Using lentivirus transfection, we established <i>SMAD7</i>-knockdown human dental papilla stem cells, which manifested remarkably blunt proliferation rate, along with diminished Wnt signaling activity. In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation. Mechanistically, we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays. Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities, indicating both direct and indirect regulatory mechanisms. These findings highlight the critical role of SMAD7 in the proliferation and differentiation of human dental stem cells, which could contribute to dental tissue regeneration and engineering.</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

SMAD7 regulates the canonical Wnt signaling through TGF-β cascade crosstalk and SMAD7/β-CATENIN transcription factor complex formation during tooth regeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月6日

查看全文
  • Qiuyu Chen,
  • Zhi Liu,
  • Bohuai Zhou,
  • Cheng Liang,
  • Yiping Chen,
  • Weidong Tian,
  • Tian Chen

摘要

Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation, apoptosis, and differentiation, with the Wnt/β-catenin signaling pathway playing a pivotal role. However, the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear. Smad7, a key antagonist of the TGF-β superfamily, is essential for maintaining tissue homeostasis and ensuring proper cellular function. Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells, resulting in small molars. Here, we identified SMAD7 expression in human dental papilla and dental pulp, colocalized with β-CATENIN and cell proliferation-related proteins. RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs. Using lentivirus transfection, we established SMAD7-knockdown human dental papilla stem cells, which manifested remarkably blunt proliferation rate, along with diminished Wnt signaling activity. In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation. Mechanistically, we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays. Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities, indicating both direct and indirect regulatory mechanisms. These findings highlight the critical role of SMAD7 in the proliferation and differentiation of human dental stem cells, which could contribute to dental tissue regeneration and engineering.