RUNX2 调控软骨细胞成熟
中文名称
通路描述
除了调控成骨细胞分化外，RUNX2 通过调控软骨细胞成熟来调节骨骼发育。软骨细胞成熟发生在内成骨过程中。甲状旁腺激素受体（PTHR1）和印度 Hedgehog（IHH）的表达是软骨细胞成熟的标志。Runx2 和 Runx3 双敲除小鼠完全缺乏软骨细胞成熟，从而导致异常肢体生长。基于小鼠研究，RUNX2 直接调控 IHH 基因的转录。RUNX2 在 IHH 基因启动子中的结合位点在人类中保守（Yoshida et al. 2004）。此外，基于小鼠研究，RUNX2 正向调控 NELL1（神经 EGFL-like 1）的转录，这是软骨生成的关键功能介质，但尚未证明 RUNX2 直接结合 NELL1 基因座（Li et al. 2017）。RUNX2 结合位点存在于小鼠 Col10a1 基因的增强子中，该基因编码 X 型胶原，是肥大软骨细胞的标志，对于内成骨至关重要。虽然 RUNX2 结合是必需的，但不足以触发 Col10a1 转录（Gu et al. 2014）。
英文描述
RUNX2 regulates chondrocyte maturation In addition to regulating osteoblast differentiation, RUNX2 regulates skeletal development by regulating maturation of chondrocytes (Takeda et al. 2001). Chondrocyte maturation happens during the process of endochondral ossification. Expression of the parathyroid hormone receptor (PTHR1) and Indian hedgehog (IHH) are hallmarks of chondrocyte maturation. Mice that are double knockouts for Runx2 and Runx3 show a complete absence of chondrocyte maturation and, hence, aberrant limb growth. Based on mouse studies, RUNX2 directly regulates transcription of the IHH gene. RUNX2 binding sites in the IHH gene promoter are conserved in humans (Yoshida et al. 2004). Also based on mouse studies, RUNX2 positively regulates transcription of NELL1 (neural EGFL-like 1), a key functional mediator of chondrogenesis, but direct binding of RUNX2 to the NELL1 gene locus has not been demonstrated (Li et al. 2017). Runx2 binding sites exist in the enhancer of the mouse Col10a1 gene, encoding type X collagen, a marker of hypertrophic chondrocytes, which is critical for endochondral bone formation. While Runx2 binding is required, it is not sufficient to trigger Col10a1 transcription (Gu et al. 2014).
所含基因
5 个基因