Abstract
After avulsion and replantation, teeth are at risk of bone and root resorption. The present study aimed to demonstrate that the intra-nuclear transducible form of transcription modulation domain of p65 (nt-p65-TMD) can suppress osteoclast differentiation in vitro, and reduce bone resorption in a rat model of tooth replantation. Cell viability and nitric oxide release were evaluated in RAW264.7 cells using CCK-8 assay and Griess reaction kit. Osteoclast differentiation was evaluated using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and tartrate-resistant acid phosphatase (TRAP) staining. Thirty-two maxillary rat molars were extracted and stored in saline (n = 10) or 10 µM nt-p65-TMD solution (n = 22) before replantation. After 4 weeks, specimens were scored according to the inflammatory pattern using micro-computed tomography (CT) imaging and histological analyses. nt-p65-TMD treatment resulted in significant reduction of nitric oxide release and osteoclast differentiation as studied using PCR and TRAP staining. Further, micro-CT analysis revealed a significant decrease in bone resorption in the nt-p65-TMD treatment group (p < 0.05). Histological analysis of nt-p65-TMD treatment group showed that not only bone and root resorption, but also inflammation of the periodontal ligament and epithelial insertion was significantly reduced. These findings suggest that nt-p65-TMD has the unique capabilities of regulating bone remodeling after tooth replantation.
Highlights
Introduction published maps and institutional affilTooth avulsion is defined as the complete dislocation of tooth from the alveolar socket as a result of trauma, and it is characterized by compromised neurovascular supply, pulp necrosis, and loss of periodontal ligament (PDL) cells [1]
This study aimed to investigate the effect of interactomic inhibition of endogenous p65 on the secretion of inflammatory cytokines and osteoclast differentiation after tooth replantation
To modulate p65-mediated NF-κB functions, we generated transducible fusion protein (p65-transcription modulation domain (TMD)) of p65 with Hph-1-protein transduction domain (PTD) (YARVRRRGPRR). nt-p65 was designed as a novel therapeutic to deliver p65-TMD efficiently into the nucleus of the cells in vitro and in vivo
Summary
Tooth avulsion is defined as the complete dislocation of tooth from the alveolar socket as a result of trauma, and it is characterized by compromised neurovascular supply, pulp necrosis, and loss of periodontal ligament (PDL) cells [1]. In order to minimize the adverse effects of avulsion, root surface treatments have been investigated for their ability to preserve PDL cell vitality [1,5]. In cases of delayed tooth replantation, necrotic remnants of PDL cells stimulate the development of external root resorption, which may lead to early tooth loss [4,6].
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