节律紊乱通过Melatonin/MT1-BMAL1导致下颌骨发育不足的机制研究

颅颌面发育畸形是一种颅颌骨发育异常性疾病，在我国发病率高、危害严重。因此，探究颅颌面畸形的发病机理，实现颅颌面畸形的早期防治，是当今发育学领域研究的热点。软骨内成骨是颅颌面发育最重要的成骨方式之一。研究表明生物节律在各组织发育过程中具有重要作用，节律紊乱是影响颅颌面发育的一种重要环境性危险因素。同时，我们前期研究也证实钟基因Bmal1敲除后，下颌骨髁突出现短小畸形，软骨内成骨序列性分化过程明显被抑制。据此，我们提出通过纠正节律紊乱防治颅颌面畸形的防治理论。本研究基于软骨内成骨中心的生物节律，通过改变光照构建环境性紊乱模型，阐明环境性节律紊乱对软骨内成骨的影响，并重点揭示环境性节律紊乱影响软骨内成骨的分子机制，探索纠正节律防治颅颌面发育畸形的的潜能，为临床上防治颅颌面发育畸形提供新思路。

Craniomaxillofacial dysplasia is a disorder of skull and jaw development, which has a high incidence and serious harm in our country. Therefore, exploring the pathogenesis of craniofacial deformities and realizing the early prevention and treatment of craniofacial deformities is a hot spot in the field of development. Endochondral ossification is one of the most important osteogenesis methods for craniomaxillofacial development. Studies have shown that the circadian rhythm system plays an important role in the development of various tissues, and circadian dysrhythmia is an important environmental risk factor affecting cranio-maxillofacial development. At the same time, our previous studies also confirmed that after Bmal1 knockout, endochondral ossification was significantly reduced, and the mandibular condyle showed short deformities. Based on this, we propose the prevention and treatment theory of cranio-maxillofacial deformities by correcting circadian dysrhythmia. Based on the circadian rhythm of the endochondral ossification center, this study will construct an environmental circadian dysrhythmia model by changing the light, clarify the impact and molecular mechanism of environmental circadian dysrhythmia on endochondral ossification, and explore the potential of resetting the rhythm to prevent cranio-maxillofacial deformities, this will provide new ideas for clinical prevention and treatment ofcranio-maxillofacial deformities.