CD109负反馈调节TGF-β信号通路促进PDLSCs参与正畸牙移动骨重建的机制研究

正畸牙移动机械力刺激下，牙周组织中活性TGF-β1被释放，招募牙周膜干细胞（PDLSCs）至骨吸收区参与骨重建。然而，多项研究表明过度激活的TGF-β信号通路抑制PDLSCs成骨分化，干扰骨重建。CD109是新近发现的TGF-β负向受体，促进TGF-βRI降解抑制TGF-β信号通路，然而其在正畸牙移动中的作用不明确。课题组前期发现：PDLSCs比其它牙源性干细胞高表达CD109；正畸牙移动中，牙周组织中CD109明显上调，而TGF-βI型受体（TGF-βRI）表达相对较弱。据此，本课题提出假设：CD109负反馈调节TGF-β信号通路使其维持低激活状态，促进PDLSCs成骨分化，是正畸牙移动骨重建的新机制。本课题首先验证CD109与正畸牙移动骨重建的相关性，进一步探索CD109负反馈调控TGF-β信号通路促进PDLSCs成骨分化的机制，为加速正畸牙移动、减少牙槽骨吸收等临床目标提出新思路。

Under the mechanical stimulation during orthodontic tooth movement, the active TGF-β1 in periodontal tissue was released, recruiting periodontal ligament stem cells (PDLSCs) to the bone resorption area to participate in bone reconstruction. However, many studies have shown that over activated TGF-β signaling pathway inhibits the osteogenic differentiation of PDLSCs and interferes with bone remodeling. CD109 is a newly discovered negative receptor of TGF-β, which promotes the degradation of TGF-β RI to inhibit TGF-β signaling pathway. However, its role and mechanism in orthodontic tooth movement are not clear. Our previous study revealed that PDLSCs higher expressed CD109 than other odontogenic stem cells. We also found that during orthodontic tooth movement, the expression of CD109 in periodontal tissue was significantly up-regulated, but the expression of TGF-β I receptor (TGF-β RI) was relatively weak. Therefore, we hypothesized that CD109 maintain TGF-β signaling pathway in a low activated state by a negative feedback regulatory loop, promoting the osteogenic differentiation of PDLSCs, which is a new mechanism of bone remodeling during orthodontic tooth movement. In this study, we first verified the correlation between CD109 and bone remodeling during orthodontic tooth movement, and further explored the mechanism of CD109 as a negative feedback regulator of TGF-β signaling pathway to promote the osteogenic differentiation of PDLSCs, so as to propose new ideas for accelerating orthodontic tooth movement and reducing alveolar bone resorption in orthodontic clinic.