NF-κB Decoy ODN-Loaded Poly(Lactic-co-glycolic Acid) Nanospheres Inhibit Alveolar Ridge Resorption.
Albert Chun-Shuo HuangYuji IshidaKai LiDuantawan RintanalertKasumi Hatano-SatoShuji OishiJun HosomichiRisa Usumi-FujitaHiroyuki YamaguchiHiroyuki TsujimotoAiko SasaiAyaka OchiHajime WatanabeTakashi OnoPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- nuclear factor
- bone regeneration
- bone mineral density
- bone loss
- signaling pathway
- toll like receptor
- postmenopausal women
- lps induced
- drug delivery
- oxidative stress
- gene expression
- pi k akt
- body composition
- transforming growth factor
- soft tissue
- inflammatory response
- poor prognosis
- drug release
- rheumatoid arthritis
- dna methylation
- cancer therapy
- binding protein
- risk assessment
- squamous cell carcinoma
- weight gain
- cell free
- climate change
- artificial intelligence
- high resolution
- transcription factor
- immune response
- single molecule
- lymph node
- replacement therapy