Osteoprotegerin-Knockout Mice Developed Early Onset Root Resorption.
BACKGROUND
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.
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Yi
Y
Liu
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Haiming
H
Du
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Yunfei
Y
Wang
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Mengmeng
M
Liu
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Shijian
S
Deng
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Linlin
L
Fan
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Lili
L
Zhang
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Yao
Y
Sun
Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. Electronic address: 332076986@qq.com.
Qi
Q
Zhang
D000818:Animals; D003739:Dental Cementum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008334:Mandible / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008963:Molar / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000172:deficiency* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D012391:Root Resorption / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse
Cementum; OPG; osteoclast; root resorption