Department of Surgery, The Children's Hospital of Philadelphia Research Institute, 3615 Civic Center Boulevard, Abramson Research Center, 902 Philadelphia, PA 19104, USA.
J Dent Res. 2011 May;90(5):625-31. doi: 10.1177/0022034510397836. Epub 2011 Feb 4.
Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.
联合次级软骨对于下颌骨的发育很重要，但形成次级软骨的分子机制在很大程度上仍不清楚。在这里，我们探讨了印度刺猬（Ihh）是否调节联合软骨的发育和生长。在胚胎第 16.5 天到 18.5 天， Sox9 表达的软骨细胞在 Tgfβ-1/Runx2 表达的间充质细胞的凝聚处形成，在潜在的联合关节部位形成具有明显 Ihh、胶原蛋白 X 和骨桥蛋白表达模式的生长板样结构。在出生后，表达 Ihh 受体 Patched1 的间充质细胞位于表达 Ihh 的次级软骨的前部，增殖、分化为软骨细胞，并有助于牙槽骨的前部生长。然而，在 Ihh 缺失的小鼠中，联合发育存在缺陷，主要是由于软骨细胞成熟增强和软骨祖细胞增殖减少。在双重 Ihh；Gli3 突变体中，增殖部分得到恢复，这表明 Gli3 通常是联合发育的负调节剂。因此，Ihh 信号对于联合软骨的发育和下颌骨的前部生长是必不可少的。
