Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Antioxid Redox Signal. 2009 Sep;11(9):2065-75. doi: 10.1089/ars.2008.2355.
Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.
核因子-κB（NF-κB）参与破骨细胞的分化和激活。因此，阻断 NF-κB 通路可能是治疗骨代谢疾病的一种新的治疗策略。牙周炎是由细菌感染引起的龈下炎症；这种疾病也被认为是导致全身疾病的慢性焦点。在这项研究中，NF-κB 诱饵寡脱氧核苷酸（ODN）被局部应用于实验性牙周炎的碎屑堆积模型和骨缺损模型中的伤口愈合，以研究诱饵 ODN 对骨代谢的影响。NF-κB 诱饵 ODN 的应用显著降低了龈沟液中的白细胞介素-6 活性，并改善了 X 光片和 DEXA 分析中的牙槽骨丧失。对失去牙槽骨支持的暴露根的直接测量表明，NF-κB 诱饵治疗显著保护了骨丢失。在骨缺损模型中，与对照 scrambled 诱饵相比，NF-κB 诱饵 ODN 促进了愈合过程，在 micro-CT 分析中。总体而言，通过抑制破骨细胞的骨吸收，诱饵策略抑制 NF-κB 可防止牙周炎中骨丢失的进展，并促进骨缺损中的伤口愈合。针对 NF-κB 可能是各种骨代谢疾病的潜在治疗方法。
