MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in cementoblasts

Abstract

Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated cementoblasts, whereas proinflammatory molecules increased.The mouse periapical lesions have similar results, which imitate an inflammatory environment for cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6).Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in cementoblasts. K E Y W O R D Sapoptosis, cementum, IL-6, miRNA, periodontitis

Diagnostic biomarker candidates for pulpitis revealed by bioinformatics analysis of merged microarray gene expression datasets

“…Miyuki Azuma et al studied the immune responses in mouse dental pulp, and founded that expression of CD86 were enhanced in dental pulp after cusp trimming, but disappeared within 2 h and migrated into regional lymph nodes at 24 h after acid treatment [30]. As chemokines launch and boost the process of inflammation, an increased expression of CCL2 was observed in chronic periapical lesions, indicating the association between chemokines and dental pulp inflammation [31,32] In addition, IL6, TLR8, CXCL8, MMP9, and ICAM1 are also associated with immunity and inflammation in dental pulp as reported [1,[33][34][35][36][37]…”

Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway

“…3). Recent studies have shown that miR-181b-5p plays an important role in regulating cell proliferation, apoptosis [15], and the immune inflammatory response [16]. miR-181b-5p expression was upregulated in Exosome-MS ( Fig.…”

Diagnostic biomarker candidates for pulpitis revealed by bioinformatics analysis of merged microarray gene expression datasets

“…Accordingly, increased expression of CCL2 has been observed in chronic periapical lesions, indicating an association between chemokines and dental pulp in ammation [46,47]. In addition, IL6, MMP9, TLR8, CXCL8, and ICAM1 have been reported to be associated with immunity and in ammation in dental pulp [1,17,[48][49][50][51].…”