覆盖于根面的牙周膜、牙骨质和马拉瑟上皮剩余是牙根的重要保护因素，对牙根均有重要保护作用。这些因素被破坏，牙根吸收可能发生。骨保护素（osteoprotegerin, OPG）是抑制骨吸收的关键保护分子，但其在牙根吸收重要保护因素中的作用尚无系统研究。我们前期实验发现小鼠牙周膜和马氏上皮剩余表达OPG；敲除OPG后小鼠牙根发生根吸收，并随年龄增长逐渐加重，同时牙骨质形成厚度减少、牙周膜纤维紊乱、马氏上皮剩余数量明显减少、破骨细胞数目增多。我们利用OPG基因敲除小鼠构建替代性牙根外吸收模型，发现其较野生型鼠更早发生牙根吸收，且吸收程度更重。本项目将在前期实验的基础上，通过在、离体实验，敲减和过表达OPG，以及建立牙根吸收疾病模型，进一步探讨OPG在牙根重要保护因素发育和维持中的作用和可能机制；并通过引入外源性OPG “挽救”根吸收表型，深入认识其多重保护作用，为牙根吸收预防和治疗提供理论依据。

Periodontal ligament (PDL), cementum, and the epithelial rests of Malassez (ERM) covering the root surface play vital roles in protecting against root resorption. Once these critic protection elements were damaged, root resorption would occur. Osteoprotegerin (OPG) has revealed as a powerful inhibitor of bone resorption. However, the protective effects of OPG in cementum, PDL and ERM against root resorption are still unknown. Our preliminary experiments found that OPG was expressed in mouse PDL and ERM. Osteoprotegerin-deficient (OPG-/-) mice displayed a progressive and extensive root resorption with aging, accompanied by a significant reduction in cementum formation and ERM numbers, disorders of PDL, and an increase of osteoclast formation. In addition, we examined external replacement resorption in OPG-/- and wild-type (WT) mice. In OPG-/- mice, the root resorption was earlier and more severe compared to those in WT mice. Based on these findings, by OPG knockdown or overexpression in vivo and in vitro, we further focus on the effects of OPG on root development and its integrity maintenance after root formation. Besides, exogenous OPG will be used to try to “rescue” the phenotype of root resorption. Our results will be helpful for clarifying the multiple protective roles of OPG on tooth development and mechanism of the protection, broadening our understanding of OPG, and developing new prevention and treatment strategies for root resorption.