Disrupted tenogenesis in masseter as a potential cause of micrognathia.
Disrupted tenogenesis in masseter as a potential cause of micrognathia.
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DOI：
10.1038/s41368-022-00196-y
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发表时间：
2022-10-18
影响因子：
14.9
通讯作者：
Xiao, Jing
中科院分区：
文献类型：
--
作者：
Liu, Chao;Zhou, Nan;Li, Nan;Xu, Tian;Chen, Xiaoyan;Zhou, Hailing;Xie, Ailun;Liu, Han;Zhu, Lei;Wang, Songlin;Xiao, Jing
小颌畸形是一种严重的影响外观和生存的颅面畸形。以往的研究表明，下颌小颌畸形的发生与颌骨成骨的多种因素有关，但对成骨以外的因素研究甚少。在目前的研究中，我们发现Osr2-cre在小鼠咬肌肌腱的推测间质中异位激活Fgf8导致小颌畸形、咬肌退化以及咬肌肌腱的模式和分化被破坏。因为Myf5-cre;Rosa26R-Fgf8小鼠咬颌骨和下颌骨发育正常，排除了Fgf8过表达直接导致小颌畸形和咬颌骨退化的可能性。进一步的研究表明，一系列软骨形成标志物在发育中的Osr2-cre中被异位激活；Rosa26R-Fgf8咬肌肌腱，而咬肌和下颌骨的机械感明显降低。因此，提示Osr2-cre中的小颌类；Rosa26R-Fgf8小鼠继发源于传递到下颌骨的机械力减少。同样，当从发育中的下颌骨中剔除致腱性或致肌性成分时，小颌畸形和咬肌退行性变都伴随着下颌骨的机械感觉下降，这证实了咬肌肌腱传递的机械力的丧失可能导致小颌畸形。此外，由肌腱生成中断引起的小颌畸形似乎是由于成骨规范受损，而不是骨膜祖细胞的分化。我们的发现揭示了一种新的下颌形态发生机制，为小颌畸形的预防和治疗提供了新的思路。
Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
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影响因子：
2.7
作者：
Gao Y;Lan Y;Liu H;Jiang R
通讯作者：
Jiang R
DOI：
10.1016/j.ijporl.2019.109842
发表时间：
2020-04-01
影响因子：
1.5
作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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