Sun Lin, Wang Jie, Chen Shuo, He Yang
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China.
National Clinical Research Center for Oral Disease, Beijing 100081, China.
Int J Mol Sci. 2025 Apr 9;26(8):3508. doi: 10.3390/ijms26083508.
Sutures such as fibrous joints in craniofacial bones provide a niche for Gli1+ mesenchymal stem cells (MSCs) in promoting calvarial bone development and growth. However, the underlying molecular mechanism behind the fate of the Wnt/β-catenin regulation of Gli1+ MSCs during calvarial bone formation remains unclear. Here, we showed that β-catenin was colocalized with Gli1+ lineage cells near the osteogenic front within a suture, and postnatal skull development was delayed via a conditional knockout of in Gli1+ MSCs. Calcein-Alizarin Red dual staining revealed that Wnt/β-catenin signal inhibition impaired the rate of bone formation. Furthermore, immunofluorescent staining indicated that Wnt/β-catenin signaling was crucial in facilitating the proliferative capacity of Gli1+ MSCs and their commitment to the osteogenic lineage. Notably, activating hedgehog (Hh) signaling partially restored the suture morphology in knockout mice. Collectively, our findings revealed the crosstalk between Wnt and Hh signaling modulates the fate of Gli1+ MSCs during calvarial bone formation.
颅面骨中的纤维性关节等缝线为Gli1+间充质干细胞（MSC）提供了一个微环境，以促进颅骨的发育和生长。然而，在颅骨形成过程中，Wnt/β-连环蛋白对Gli1+ MSC命运调控的潜在分子机制仍不清楚。在这里，我们发现β-连环蛋白与缝线内成骨前沿附近的Gli1+谱系细胞共定位，并且通过条件性敲除Gli1+ MSC中的 ，出生后颅骨发育延迟。钙黄绿素-茜素红双重染色显示，Wnt/β-连环蛋白信号抑制会损害骨形成速率。此外，免疫荧光染色表明，Wnt/β-连环蛋白信号传导对于促进Gli1+ MSC的增殖能力及其向成骨谱系的分化至关重要。值得注意的是，激活刺猬（Hh）信号通路部分恢复了 敲除小鼠的缝线形态。总的来说，我们的研究结果揭示了Wnt和Hh信号通路之间的相互作用调节了颅骨形成过程中Gli1+ MSC的命运。
