Inhibition of nuclear factor kappa B inducing kinase suppresses inflammatory responses and the symptoms of chronic periodontitis in a mouse model

• Published in: The international journal of biochemistry & cell biology 2021-10, Vol.139, p.106052, Article 106052
• Main Authors: Wang, Jianqi, Wu, Shuainan, Li, Zhaobao, Liu, Lu, Pang, Ying, Wei, Jianming
• Format: Article
• Language: English
• Subjects: Animals; Chronic Periodontitis - drug therapy; Chronic Periodontitis - genetics; Chronic Periodontitis - metabolism; Chronic Periodontitis - pathology; Disease Models, Animal; inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - metabolism; NF-kappaB-Inducing Kinase; NIK-inhibitor; non-canonical NF-κB pathway; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis - drug effects; periodontitis; Protein Kinase Inhibitors - pharmacology; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Signal Transduction - drug effects
• ISSN: 1357-2725; 1878-5875; 1878-5875
• DOI: 10.1016/j.biocel.2021.106052

Chronic periodontitis is an inflammatory disease that represents a major public health issue nowadays. Here, we investigated the protective role of nuclear factor kappa B (NF-κB) inducing kinase (NIK)-inhibitor on chronic periodontitis and revealed the underlying molecular mechanism. NIK-inhibitor was synthesized, and its functions were examined in primary osteoclasts and wild-type (WT) and NIK-/- chronic periodontitis mouse model. Lipopolysaccharides (LPS) or activator of NF-κB was applied to stimulate inflammatory response of osteoclasts. The qRT-PCR, ELISA and Western blot were used to measure the expression of pro-inflammatory and osteoclast-related genes, and the activation of NF-κB signaling. Osteoclastogenesis and bone damage were detected by TRAP staining and micro-CT. NIK knockdown mice had lower expression of osteoclast-related genes and improved CEJ-ABC damage. Similarly, NIK-inhibitor administration inhibited inflammatory responses and CEJ-ABC damage in chronic periodontitis models. NIK-inhibitor suppressed osteoclastogenesis and osteoclast-related genes expression through inhibiting the non-canonical NF-κB signaling. NIK plays important role in bone destruction of chronic periodontitis and NIK-inhibitor represents a promising therapeutic strategy for this disease.