Scholarlink

<p>The cranial base synchondroses, comprised of opposite-facing bidirectional chondrocyte layers, drive anteroposterior cranial base growth. In humans, <i>RUNX2</i> haploinsufficiency causes cleidocranial dysplasia associated with deficient midfacial growth. However, how RUNX2 regulates chondrocytes in the cranial base synchondroses remains unknown. To address this, we inactivated <i>Runx2</i> in postnatal synchondrosis chondrocytes using a tamoxifen-inducible <i>Fgfr3-creER</i> (Fgfr3-Runx2<sup>cKO</sup>) mouse model. Fgfr3-Runx2<sup>cKO</sup> mice displayed skeletal dwarfism and reduced anteroposterior cranial base growth associated with premature synchondrosis ossification due to impaired chondrocyte proliferation, accelerated hypertrophy, apoptosis, and osteoclast-mediated cartilage resorption. Lineage tracing reveals that <i>Runx2</i>-deficient Fgfr3<sup>+</sup> cells failed to differentiate into osteoblasts. Notably, <i>Runx2</i>-deficient chondrocytes showed an elevated level of FGFR3 and its downstream signaling components, pERK1/2 and SOX9, suggesting that RUNX2 downregulates FGFR3 in the synchondrosis. This study unveils a new role of <i>Runx2</i> in cranial base chondrocytes, identifying a possible RUNX2-FGFR3-MAPK-SOX9 signaling axis that may control cranial base growth.</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

RUNX2 is essential for maintaining synchondrosis chondrocytes and cranial base growth

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月29日

查看全文
  • Shawn A. Hallett,
  • Ashley Dixon,
  • Isabella Marrale,
  • Lena Batoon,
  • José Brenes,
  • Annabelle Zhou,
  • Ariel Arbiv,
  • Vesa Kaartinen,
  • Benjamin Allen,
  • Wanida Ono,
  • Renny T. Franceschi,
  • Noriaki Ono

摘要

The cranial base synchondroses, comprised of opposite-facing bidirectional chondrocyte layers, drive anteroposterior cranial base growth. In humans, RUNX2 haploinsufficiency causes cleidocranial dysplasia associated with deficient midfacial growth. However, how RUNX2 regulates chondrocytes in the cranial base synchondroses remains unknown. To address this, we inactivated Runx2 in postnatal synchondrosis chondrocytes using a tamoxifen-inducible Fgfr3-creER (Fgfr3-Runx2cKO) mouse model. Fgfr3-Runx2cKO mice displayed skeletal dwarfism and reduced anteroposterior cranial base growth associated with premature synchondrosis ossification due to impaired chondrocyte proliferation, accelerated hypertrophy, apoptosis, and osteoclast-mediated cartilage resorption. Lineage tracing reveals that Runx2-deficient Fgfr3+ cells failed to differentiate into osteoblasts. Notably, Runx2-deficient chondrocytes showed an elevated level of FGFR3 and its downstream signaling components, pERK1/2 and SOX9, suggesting that RUNX2 downregulates FGFR3 in the synchondrosis. This study unveils a new role of Runx2 in cranial base chondrocytes, identifying a possible RUNX2-FGFR3-MAPK-SOX9 signaling axis that may control cranial base growth.