Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan.
Department of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Mol Sci. 2023 Feb 12;24(4):3699. doi: 10.3390/ijms24043699.
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.
拔牙导致的剩余牙槽嵴吸收和体积丧失与早期过度炎症有长期相关性。核因子-κB（NF-κB）寡脱氧核苷酸（ODN）是一种双链 DNA 序列，能够下调 NF-κB 通路下游基因的表达，该通路被认为可以调节典型的促炎信号、生理骨代谢、病理性骨破坏和骨再生。本研究旨在探讨 NF-κB 寡脱氧核苷酸通过聚乳酸-羟基乙酸共聚物（PLGA）纳米球给药对 Wistar/ST 大鼠拔牙窝的治疗效果。用 NF-κB 寡脱氧核苷酸负载 PLGA 纳米球（PLGA-NfDs）治疗后进行 microCT 和小梁骨分析显示，垂直牙槽骨丧失得到抑制，骨量增加，小梁骨表面更光滑，小梁骨更厚，小梁数和分离度更大，骨孔隙率更少。组织形态计量学和逆转录定量聚合酶链反应分析显示，抗酒石酸酸性磷酸酶表达的破骨细胞、白细胞介素-1β、肿瘤坏死因子-α、NF-κB 配体受体激活剂、周转率减少，而转化生长因子-β1 免疫阳性反应和相对基因表达增加。这些数据表明，通过 PLGA-NfD 进行局部 NF-κB 寡脱氧核苷酸转染可以有效抑制愈合过程中拔牙窝的炎症，并有加速新骨形成的潜力。
