Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice
Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice
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骨细胞中的外源性 FGF8 信号导致小鼠下颌发育不全
DOI：
10.1111/odi.13262
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发表时间：
2020
期刊：
影响因子：
3.8
通讯作者：
Shao Meiying
中科院分区：
文献类型：
--
作者：
Xu Jue;Wang Linyan;Huang Zhen;Chen YiPing;Shao Meiying
目的成纤维细胞生长因子8 （FGF8）信号在颅面成骨过程中起重要作用。本研究旨在探讨胚胎发生过程中FGF8信号通路改变在上颌下颌骨发育中的作用。Dmp1(Cre)；生成R26R（mTmG）小鼠，追踪Dmp1（+）细胞系，Dmp1(Cre)；R26R（Fgf8）小鼠是为了探索Dmp1（+）细胞中Fgf8信号增强对成骨的影响，重点是在胚胎发生过程中上颌下颌骨的发育，通过全坐骨染色、组织学和免疫染色进行评估。同时检测细胞增殖率和成骨基因的表达。结果产前上颌下颌骨骨细胞Dmp1阳性，Fgf8在Dmp1（+）细胞中过表达导致下颌骨发育不全。而Dmp1（Cre）等位基因早在E13.5时就在发育中的下颌骨骨细胞中起作用，且Dmp1（Cre）在下颌骨成骨区细胞增殖率增强；R26R（Fgf8）小鼠在E14.5时，组织学检查显示成骨最初在E15.5时受到影响，同时成骨分化标志物受到抑制。结论FGF8信号在Dmp1（+）细胞中的增强可导致下颌骨成骨不足，导致下颌骨发育不全。
Objective Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. Materials and Methods Dmp1(Cre);R26R(mTmG) mice were generated to trace Dmp1(+) cell lineage, and Dmp1(Cre);R26R(Fgf8) mice were generated to explore the effects of augmented FGF8 signaling in Dmp1(+) cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. Results Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1(+) cells led to mandibular hypoplasia. While Dmp1(Cre) allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1(Cre);R26R(Fgf8) mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. Conclusions Augmented FGF8 signaling in Dmp1(+) cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.