Inhibition of nuclear factor kappa B inducing kinase suppresses inflammatory responses and the symptoms of chronic periodontitis in a mouse model
2021
Wang, Jianqi | Wu, Shuainan | Li, Zhaobao | Liu, Lu | Pang, Ying | Wei, Jianming
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.
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