NF-κB Decoy ODN-Loaded Poly(Lactic-co-glycolic Acid) Nanospheres Inhibit Alveolar Ridge Resorption

Abstract

Residual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides (ODNs) are double-stranded DNA sequences capable of downregulating the expression of downstream genes of the NF-κB pathway, which is recognized for regulating prototypical proinflammatory signals, physiological bone metabolism, pathologic bone destruction, and bone regeneration. The aim of this study was to investigate the therapeutic effect of NF-κB decoy ODNs on the extraction sockets of Wistar/ST rats when delivered by poly(lactic-co-glycolic acid) (PLGA) nanospheres. Microcomputed tomography and trabecular bone analysis following treatment with NF-κB decoy ODN-loaded PLGA nanospheres (PLGA-NfDs) demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription–quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1β, tumor necrosis factor-α, receptor activator of NF-κB ligand, turnover rate, and increased transforming growth factor-β1 immunopositive reactions and relative gene expression. These data demonstrate that local NF-κB decoy ODN transfection via PLGA-NfD can be used to effectively suppress inflammation in a tooth-extraction socket during the healing process, with the potential to accelerate new bone formation.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement

“…In continuation of our previous research, naked scrambled ODNs (ScD), structured as phosphorothioated double-stranded ScD with sequences 5 ′ -TTGCCGTACCTGACTTAGCC-3 ′ and 3 ′ -AACGGCATGGACTGAATCGG-5 ′ , and NF-κB-targeting ODNs (NfD), structured as phosphorothioated double-stranded NfD with sequences 5 ′ -CCTTGAAGGGATTTCCCTCC-3 ′ and 3 ′ -GGAACTTCCCTAAAGGGAGG-5 ′ , were used as previously described [17]. The concentrations of ScD and NfD in solutions containing ScD and NfD, as well as in PLGA-ScD and PLGA-NfD solutions, respectively.…”

“…Reconstruction of the appropriate alveolar bone mass along with periodontal regeneration is crucial in facilitating OTM and tooth translation during extraction space closure, in addition to the proper orthodontic alignment of neighboring teeth at the extraction site [22,23]. Our previous study demonstrated the healing effect of PLGA-NfDs on the first-stage tooth-extraction socket in vivo [17]. In the current study, we explored the effect of the PLGA-NfD on the regulation of alveolar bone resorption and periodontal regeneration during OTM in rats subjected to orthodontic forces.…”

“…A previous in vitro study showed that NF-κB-decoy ODNs can inhibit osteoclast development and activation and that they can attenuate bone resorption as well as femur and tibia destruction when injected into rats with osteoporosis [15]. Moreover, local delivery of NF-κB-targeting ODNs has also proven effective in treating rheumatoid arthritis, periodontal bone defects, and extraction alveolar socket repair [16,17].…”

“…Moreover, the long-term effects of decoy ODNs are determined by the stability and efficiency with which they are transported to the target tissues and absorbed by target cells. We previously reported that administration of NF-κB-decoy ODN-loaded PLGA NS (PLGA-NfDs) suppresses the inflammatory response and promotes bone regeneration over the alveolar ridge following tooth extraction in rats [17]. Given the unresolved issue of the resorptive ridge, we explored the therapeutic effect of PLGA-NfDs on the OTM biological response following tooth extraction, focusing on periodontal regeneration.…”

Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration

“…This ligand exhibits the ability to entrap the NF-κB transcription factor, thereby effectively inhibiting its pro-inflammatory activity [ 93 ]. Huang et al showed that PLGA NPs modulated with NF-κB decoy can inhibit inflammation of the extracted tooth socket, which is triggered by exaggerated osteoclast activity, and also improve alveolar bone healing [ 94 ]. Another study displayed that curcumin-loaded PLGA NPs conjugated with folic acid are effective in targeting cancer cells expressing folate receptors, while in vivo they resulted in tumor size reduction in a mouse model [ 95 ].…”