Zhang Hongrong, Shen Shiying, Qian Yemei, Zhang Liqin, Pu Jiantong, Zhou Xue, Yang Na, Wang Weihong
Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China.
Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Center of Stomatology, Affiliated Hospital of Yunnan University, Kunming, Yunnan, China.
Int Dent J. 2025 Aug 27;75(6):103874. doi: 10.1016/j.identj.2025.103874.
Craniofacial malformations, caused by dysregulated neural crest cell (NCC) differentiation, affect approximately one-third of newborns worldwide. Although TGFB3 mutations were recently associated with human coronoid process hypertrophy (CPH) and other craniofacial disorders, the mechanisms by which TGF-β3 regulates NCC fate determination through cell-cell communication remains unknown.
A zebrafish model was used to investigate the impact of tgfb3 on craniofacial cartilage and bone development. Additionally, Tgfb3 was knocked down in neural crest stem cells (NCSCs) in vitro to observe cellular changes and effects on chondrogenic and osteogenic differentiation.
Knockdown of tgfb3 in zebrafish resulted in impaired cartilage development and bone formation, which was associated with the TGF-β signaling pathway. A reduction in the expression of markers for neural crest cell formation, migration, and differentiation was observed. Although Tgfb3 knockdown did not affect the proliferation capacity of NCSCs, it led to increased apoptosis, reduced migration, and decreased chondrogenic and osteogenic differentiation. The expression of osteogenesis-related proteins and TGF-β/Smad pathway-related proteins was also reduced in NCSCs to varying degrees.
Silencing the Tgfb3 gene in zebrafish led to significant impairment in craniofacial cartilage and bone development, clearly highlighting the critical role of TGF-β3 in regulating NCSC fate. These findings underscore the importance of TGF-β3 in maintaining NCSC migration and differentiation.
由神经嵴细胞（NCC）分化失调引起的颅面畸形影响着全球约三分之一的新生儿。尽管最近发现TGFB3突变与人类喙突肥大（CPH）及其他颅面疾病有关，但TGF-β3通过细胞间通讯调节NCC命运决定的机制仍不清楚。
使用斑马鱼模型研究tgfb3对颅面软骨和骨骼发育的影响。此外，在体外敲低神经嵴干细胞（NCSCs）中的Tgfb3，以观察细胞变化以及对软骨生成和成骨分化的影响。
在斑马鱼中敲低tgfb3导致软骨发育和骨形成受损，这与TGF-β信号通路有关。观察到神经嵴细胞形成、迁移和分化标志物的表达减少。虽然敲低Tgfb3不影响NCSCs的增殖能力，但导致细胞凋亡增加、迁移减少以及软骨生成和成骨分化降低。NCSCs中与成骨相关的蛋白和与TGF-β/Smad通路相关的蛋白表达也不同程度降低。
在斑马鱼中沉默Tgfb3基因导致颅面软骨和骨骼发育显著受损，清楚地突出了TGF-β3在调节NCSC命运中的关键作用。这些发现强调了TGF-β3在维持NCSC迁移和分化中的重要性。
