The Wnt/β-catenin signaling pathway has a healing ability for periapical periodontitis

Abstract

Various disease-related genes have recently been identified using single nucleotide polymorphisms (SNPs). This study identified disease-related genes by analyzing SNP using genomic DNA isolated from Japanese patients with periapical periodontitis. Results showed that the SNP in LRP5 demonstrated a significant genotypic association with periapical lesions (Fisher’s exact test, P < 0.05). We constructed an in vivo murine periapical periodontitis model to confirm the Wnt/β-catenin signaling pathway’s role in developing and healing periapical periodontitis. We observed that administration of the Wnt/β-catenin signaling pathway inhibitor enlarged the periapical lesion. Moreover, applying lithium chloride (LiCl) to root canals accelerated periapical periodontitis healing. Histological analysis demonstrated that the expression levels of Col1a1 and Runx2 increased in the LiCl application group compared to that in the control group. Furthermore, many CD45R-positive cells appeared in the periapical lesions in the LiCl application group. These results indicated that LiCl promoted the healing of periapical periodontitis by inducing bone formation and immune responses. Our findings suggest that the Wnt/β-catenin signaling pathway regulates the development of periapical periodontitis. We propose a bioactive next-generation root canal treatment agent for this dental lesion.

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

“…Wnt signaling is a vital regulatory pathway in osteoblast differentiation . The regulation of Wnt/b-catenin signaling pathway inhibitors intensifies periapical lesions (Naruse et al, 2021). The effect of Wnt3a treatment on osteogenic function is temporally dichotomous (Tang et al, 2014).…”

Lithium carbonate accelerates the healing of periapical periodontitis

“…To clarify the Wnt/ β-catenin pathway's role in the development of periapical periodontitis, we performed the root canal treatment on mice with induced periapical periodontitis in our previous study. The results of our in vivo experiments demonstrated that the application of LiCl into root canals accelerated the healing of periapical periodontitis 10 . Thus, these results imply that lithium ion (Li + ) diffused from LiCl has the healing ability for periapical periodontitis.…”

“…Our recent work demonstrated that the A1330V variant of LRP5 was associated with the development of periapical periodontitis 10 . According to the results of the SNP analysis, we speculated that the Wnt/βcatenin signaling pathway was associated with periapical periodontitis.…”

“…Since we observed some cases in which periapical lesions did not form even if root canal cleaning and lling conditions were inadequate, we speculated that there may be individual differences in the development of periapical periodontitis. Our recent report demonstrated that the A1330V variant of LRP5 (LDL Receptor Related Protein 5), which was one of the co-receptors of Wnt proteins in the canonical Wnt pathway, was associated with periapical periodontitis 10 . The Wnt/βcatenin signaling pathway has been shown to be involved in somatic axis formation during ontogeny and in the development of various diseases, including cancer [11][12][13] .…”

Canonical Wnt/β‐catenin signaling has positive effects on osteogenesis, but can have negative effects on cementogenesis

“…10 A recent study on periapical cementum demonstrated that administration of the Wnt/β-catenin inhibitor enlarged the periapical lesion, while applying lithium chloride to root canals accelerated periapical periodontitis healing. 46 These seemingly contradictory results can potentially be explained by the impact of the Wnt signaling on periodontal ligament and cementum in the inflammatory environment since both studies used a periodontal defect model. Several studies suggest that Wnt signaling may have an opposite regulatory effect on cementogenic differentiation and mineralization between PDLCs and cementoblasts/cementocytes.…”