NIK inhibitor impairs chronic periodontitis via suppressing non-canonical NF-κB and osteoclastogenesis
NIK inhibitor impairs chronic periodontitis via suppressing non-canonical NF-κB and osteoclastogenesis
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DOI：
10.1093/femspd/ftaa045
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发表时间：
2020-10-01
影响因子：
3.3
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Wang, Jiang;Wang, Bo;Wang, Lei
牙周炎是一种引起牙周组织和牙槽骨损伤的炎症性疾病。破骨细胞的过度激活和形成会导致骨破坏，从而导致牙周炎的发展。核因子κ B配体受体激活因子（RANKL）介导的nf - κ B信号传导在破骨细胞分化中起重要作用。我们旨在研究nf - κ b诱导激酶（NIK）抑制剂NIK- smi1对体外破骨细胞形成和体内牙周炎进展的影响。采用结扎诱导的牙周炎小鼠模型，研究NIK-SMI1对牙周炎的潜在治疗作用。Western blot法和real-time PCR法分别检测靶蛋白和mRNA的表达水平。我们发现，NIK-SMI1强烈抑制rankl刺激的非规范NF-kappa B信号传导，核p52表达和活性下降。阻断NIK活性也导致破骨细胞特异性基因表达降低和ifn - β表达增强。NIK-SMI1治疗可减轻牙周炎的进展和体内促炎细胞因子的表达。我们的研究表明，NIK-SMI1对体外破骨细胞生成和体内牙周炎进展具有有益的减缓作用。应用NIK-SMI1可能是治疗牙周炎的潜在方法。
Periodontitis is an inflammatory disease that causes damages to periodontium and alveolar bone. Overactivation and formation of osteoclasts can cause bone destruction, which contributes to periodontitis development. Receptor activator of nuclear factor kappa B ligand (RANKL)-mediated NF-kappa B signaling plays an essential role in osteoclasts differentiation. We aimed to study the effects of NIK-SMI1, an NF-kappa B-inducing kinase (NIK) inhibitor, on the osteoclastogenesis in vitro and periodontitis progression in vivo. A ligature-induced mice model of periodontitis was incorporated to test the potential therapeutic effect of NIK-SMI1 on periodontitis. The target protein and mRNA expression levels were determined by Western blot assay and real-time PCR assay, respectively. We found that the administration of NIK-SMI1 strongly inhibited the RANKL-stimulated non-canonical NF-kappa B signaling as demonstrated by decreased nuclear p52 expression and activity. Blocking NIK activity also resulted in reduced osteoclasts specific genes expression and enhanced IFN-beta expression. NIK-SMI1 treatment resulted in attenuated periodontitis progression and pro-inflammatory cytokines expression in vivo. Our study suggested that NIK-SMI1 exerts beneficial effects on the mitigation of osteoclastogenesis in vitro and periodontitis progression in vivo. Application of NIK-SMI1 may serve as a potential therapeutic approach for periodontitis.