髁突软骨内成骨在下颌骨生长发育和骨塑建中发挥重要作用，然而其机制不明。新近研究结果有别于经典理论，表明软骨细胞直接转化成骨是软骨内成骨的重要途径。本课题组前期研究在髁突中发现大量软骨细胞发生成骨转化，该过程与Sox2信号相关；这一发现对髁突软骨细胞在下颌骨生长发育中的角色带来了新认识，其机制有待深究。总结研究现状，我们认为应力刺激激活YAP-Sox2转录轴，可能进而通过Sox2-BMI1-BMP2诱导细胞重编程和成骨转化。为验证该假说，本课题结合体内、体外实验，采用基因修饰、化学拮抗等方法对该假说中的关键因子进行增效或失效，研究YAP-Sox2-BMI1-BMP2调控髁突软骨细胞成骨转化的机制。该研究将揭示髁突软骨细胞影响下颌骨生长发育和骨塑建的作用机理，丰富颅颌面发育学理论，通过靶向调控YAP-Sox2有望对下颌骨的生长发育进行精准有效的干预，同时为骨骼系统相关疾病治疗提供新思路。

Condylar endochondral ossification is crucial in mandibular growth and osteogenesis, though its underlying mechanism remains unclear. Recent studies observed direct transformation of condylar chondrocytes into osteoblasts in condylar osteogenesis, which shed light on the role of condylar chondrocytes during mandibular growth. Based on literature reviews and our preliminary researches, we hypothesize that stress changes in condylar micro-environment activates YAP-Sox2 axis and further induces cell reprogramming and osteogenesis through BMI1-BMP2 signaling. To test this hypothesis, we plan to synergize or invalidate key factors in the signaling cascade via genetic modification and chemical antagonism in vivo and in vitro. This study is expected to reveal the essential role of condylar chondrocyte in mandibular growth and bone modeling, and to enrich the theory of craniofacial growth and development. It is aimed to provide new insights into developing new therapies for skeletal diseases and targeted interference of mandibular growth and development.