I型糖尿病会导致患者颅颌面骨及长骨的骨质流失，抑制骨愈合，目前其骨病理学机制并不清楚。本课题组前期实验表明I型糖尿病明显降低了实验小鼠的骨愈合能力，而在此过程中Hedgehog（Hh）通路明显受到了抑制。据此我们提出，I型糖尿病可能通过抑制Hh信号通路，引起骨质流失及骨愈合能力下降。为证明假想，实验将首先使用Ins2+/-小鼠证明I型糖尿病骨质流失与Hh通路受抑制相关，且促进Hh表达可以拯救I型糖尿病导致的骨表型变化；其次通过细胞学实验方法证明促进Hh通路表达可以对抗I型糖尿病对成骨、成软骨、破骨分化的抑制作用；最后建立Ins2+/-小鼠股骨骨折及颅骨缺损模型，从软骨内成骨和膜内成骨两个方面证明促进Hh表达可以恢复I型糖尿病中被抑制的骨愈合能力。本课题旨在探讨Hedgehog通路与I型糖尿病中骨质流失和骨愈合能力下降的关系，寻求治疗I型糖尿病患者骨质流失并促进其骨愈合的新方向。

Type I diabetes causes bone loss and inhibits bone healing in human patients, the mechanism of which is not fully understood. Our previous study showed that type I diabetes significantly reduced the bone healing ability of experimental mice, and the Hedgehog (Hh) signaling pathway was significantly inhibited in this process. We propose that type 1 diabetes causes bone loss and suppresses bone healing by inhibiting the Hedgehog signaling pathway. To prove our hypothesis, Ins2+/- mice would be firstly used to demonstrate that bone loss in type 1 diabetes was associated with inhibition of the Hh pathway, and that promoting Hh expression could save the bone phenotypic changes caused by type 1 diabetes. Secondly, cytological experiments would be performed to demonstrate that promoting the expression of Hh pathway could reverse the inhibitory effects of type I diabetes on osteogenic, chondrogenic and osteoclastic differentiation. Finally, Ins2+/- mouse models of femur fracture and cranial defect would be established to demonstrate that promoting Hh expression could restore the suppressed bone healing ability in type I diabetes mellitus from both endochondral and intramembranous ossification. This study aims to explore the relationship between Hedgehog pathway and bone loss in type I diabetes, and to further seek a new direction to treat bone loss and promote bone healing in type I diabetes.