BMP1、TLL1是细胞外基质生物合成过程中重要的金属蛋白酶，两者在多种组织共同表达，且有重叠互补作用。临床报道发现BMP1基因突变患者有典型的牙本质发育不全、明显的牙槽骨吸收，提示BMP1及与其密切相关的TLL1在牙、牙周组织生长发育过程中具有重要作用。课题组在成功构建Bmp1/Tll1双基因敲除小鼠基础上，初步揭示基因敲除小鼠有牙本质发育不全、牙周炎样表型。本研究拟利用Bmp1/Tll1双基因敲除小鼠、shRNA抑制BMP1/TLL1表达的成牙本质细胞和成骨细胞系，进一步明确BMP1/TLL1在牙、牙周组织不同生长发育阶段的作用，尤其是其对细胞外基质稳态的调控机制。本研究有望系统阐明BMP1/TLL1通过调控细胞外基质稳态，维持牙本质、牙周组织正常的生长发育，并将揭示与BMP1/TLL1基因缺陷相关的牙、牙周组织疾病，为其防治提供新思路。

BMP1/TLL1, two different metalloproteinases co-expressed in various tissues with overlapping functions, are essential for extracellular matrix biosynthesis. Clinical cases reported patients with BMP1 mutation had the typical dentinogenesis imperfecta with obvious alveolar bone loss, which may indicate BMP1 and the closely related TLL1 play a crucial role in the tooth and periodontium development. Our group has successfully generated the Bmp1/Tll1 double knockout (dKO) mice and revealed the dentinogenesis imperfecta and periodontitis-like phenotypes. The aim of this study is to specify the role of BMP1/TLL1 in tooth and periodontium formation at different development stages and the regulatory mechanism of BMP1/TLL1 in extracellular matrix homeostasis using Bmp1/Tll1 dKO mice, and odontoblast and osteoblast cell lines with shRNA inhibiting BMP1/TLL1 expression. This study will systematically explain the role of BMP1/TLL1 in the dentin and periodontium development through regulating the extracellular matrix homeostasis. Additionally, it will fully uncover the tooth and periodontal diseases related to BMP1/TLL1 gene defects and provide innovative insight into the prevention and control.