Osteoprotegerin-Knockout Mice Developed Early Onset Root Resorption

Introduction: Recent studies indicate that the osteoprotegerin (OPG)/RANKL/RANK pathway takes part in root resorption. However, the relationship between OPG and root resorption is vague. The purpose of our study was to investigate the role of OPG in root resorption. Methods: The first molars of the mandibles of osteoprotegerin-knockout (Opg-KO) mice and wild-type (WT) mice were evaluated by micro computed tomography, histology, and immunohistochemistry at 4, 6, 26, and 52 weeks. To detect the activity of the osteoclasts, we induced bone marrow macrophages into osteoclast-like cells from Opg-KO mice and wild-type mice in vitro and then compared their osteoclast activities. To evaluate the cementum quality, an osteoclast-cementum co-culture model was established in vitro. Results: In Opg-KO mice, root resorption began at the age of 4 weeks. At 6 weeks the cementum damage extended to the coronal and apical regions, and at 52 weeks the damage reached the predentin. At all observed stages, more tartrate-resistant acid phosphatase (TRAP) positive cells were found on the surface of cementum in Opg-KO mice. In vitro, the mRNA levels of cathepsin K, TRAP, matrix metalloproteinase-9, and matrix metalloproteinase-1, as well as the protein expression of nuclear factor of activated T cell 1 and TRAP, increased significantly in osteoclast-like cells from Opg-KO mice. In addition, the cementum resorption pits of Opg-KO mice were larger when co-cultured with osteoclast-like cells. Conclusions: Our study demonstrated that loss of OPG led to root resorption via increasing activation of osteoclasts and reducing mineralization of cementum.