ObjectiveOrthodontic root resorption (ORR) due to orthodontic tooth movement is a difficult treatment-related adverse event. Caspases are important effector molecules for apoptosis. At present, little is known about the mechanisms underlying ORR and apoptosis in the cementum. The aim of the present in vivo study was to investigate the expression of tartrate-resistant acid phosphatase (TRAP), caspase 3, caspase 8, and receptor activator of nuclear factor kappa-B ligand (RANKL) in the cementum in response to a heavy or an optimum orthodontic force.MethodsThe maxillary molars of male Wistar rats were subjected to an orthodontic force of 10 g or 50 g using a closed coil spring. The rats were sacrificed each experimental period on days 1, 3, 5, and 7 after orthodontic force application. And the rats were subjected to histopathological and immunohistochemical analyses.ResultsOn day 7 for the 50-g group, hematoxylin and eosin staining revealed numerous root resorption lacunae with odontoclasts on the root, while immunohistochemistry showed increased TRAP- and RANKL-positive cells. Caspase 3- and caspase 8-positive cells were increased on the cementum surfaces in the 50-g group on days 3 and 5. Moreover, the number of caspase 3- and caspase 8-positive cells and RANKL-positive cells was significantly higher in the 50-g group than in the 10-g group.ConclusionsIn our rat model, ORR occurred after apoptosis was induced in the cementum by a heavy orthodontic force. These findings suggest that apoptosis of cementoblasts is involved in ORR.

Orthodontic root resorption (ORR) is one of the serious adverse events related to orthodontic treatment. Caspases are important effector molecules that mediate the process of apoptosis. However, the relationship between the mechanism underlying ORR and apoptosis in the cementum has not been clarified. In this study, human cementoblast-like cells (HCEMs) were cultured and subjected to pressure conditions assumed during orthodontic tooth movement in vitro. We then examined the effect of compressive force on caspase 3, caspase 8, receptor activator of nuclear factor -B ligand (RANKL) and osteoprotegerin(OPG)release. Furthermore, the association between root resorption and caspase was examined using z-VAD-fmk, a caspase inhibitor. In addition, we used HCEMs to examine the expression of caspase 3, caspase 8, RANKL and OPG under heavy force (HF)or optimum force(OF)in vitro. We then assessed the effects of HF with caspase inhibition using z-VAD-fmk [heavy force+inhibition(HI)group] on RANKL release from HCEMs. The application of HF induced higher levels of caspase 3 and 8 than OF. RANKL expression in cementoblasts was observed after the release of caspase 3 and 8 in the HF group. RANKL expression was significantly decreased protein production was suppressed in the HI group compared with the HF group (p < 0.05). The RANKL/OPG ratio was significantly decreased to about 57% at 9 h and 40% at 12 h in the HI group compared with the HF group(p < 0.05). These findings suggest that cementoblasts produce caspase 3 and 8 under HF conditions to activate the apoptotic pathway and then induce osteoclasts via RANKL. We considered that it as part of the mechanism involved in ORR.