IL-37 alleviates alveolar bone resorption and inflammatory response through the NF-κB/NLRP3 signaling pathway in male mice with periodontitis

Abstract

Objective: Periodontitis is an inflammatory disease, characterized by periodontal pocket formation and alveolar bone resorption, is one of the most common oral diseases. Interleukin-37 (IL-37) is a novel inflammatory suppressor that plays an important role in many inflammatory diseases. This study aimed to investigate the role of IL-37 in periodontitis DESIGN: A mouse model of periodontitis was established by Porphyromonas gingivalis. After four weeks treatment of recombinant human IL-37 (rhIL-37), the effects of IL-37 on the gingival index and tooth loosening degree of periodontitis mice were observed. H&E staining and micro-CT scanning were used to analyze the bone resorption of the maxillary. The number of osteoclasts was counted by TRAP staining and the differentiation of osteoclasts was evaluated by immunohistochemistry. The expression of inflammatory cytokines was detected by ELISA, and the protein expressions of the NF-κB/NLRP3 pathway were analyzed by WB.

Results: RhIL-37 significantly decreased the gingival index and tooth mobility degree, inhibited maxillary bone resorption, decreased the number of osteoclasts and the expression of calcitonin receptor (CTR), periodontal cathepsin K (CTSK) and receptor activator of NF-κB ligand (RANKL), and increased the expression of osteoprotegerin (OPG) in periodontitis mice. At the same time, rhIL-37 significantly decreased the expression of IL-1β, IL-6 and TNF-α, and increased the expression of IL-10 in the gingival tissue of periodontitis mice. In addition, rhIL-37 significantly inhibited the protein expressions of p-p65, NLRP3, ASC, caspase-1 and IL-1β in periodontitis mice.

Conclusion: IL-37 may alleviate alveolar bone resorption and inflammation response in periodontitis through the NF-κB/NLRP3 pathway.

Keywords: Alveolar bone resorption; IL-37; Inflammatory response; NF-κB/NLRP3 signaling pathway; Periodontitis.