Abstract

Apical periodontitis (AP) is characterized by progressive osteoclast-mediated bone destruction. Although Nell-1 may inhibit osteoclast differentiation, the underlying mechanisms and its specific role in AP remain unclear. This study aims to determine the inhibitory effects of Nell-1 on osteoclast differentiation and bone resorption in apical periodontitis. It further explores whether Nell-1 exerts its function through activation of the Wnt/β-catenin signaling pathway. RAW264.7 cells were transfected with Nell-1 to evaluate osteoclast differentiation through TRAP staining, qRT-PCR, and Western blotting. A rat model of apical periodontitis was established, followed by treatment with Nell-1 protein and the Wnt inhibitor IWR-1. The effects on bone resorption were assessed using micro-CT, histology, and TRAP staining. TRAP staining of RAW264.7 cells demonstrated that Nell-1 overexpression inhibited osteoclastogenesis. The effects were reversed by inhibiting the Wnt pathway with IWR-1. Nell-1 was found to substantially reduce bone resorption and the differentiation of osteoclasts in vivo, according to micro-CT and histological evaluations. By activating the Wnt pathway, Nell-1 effectively prevents osteoclast differentiation and bone resorption in apical periodontitis. The findings suggest that Nell-1 may serve as an adjunctive strategy for apical periodontitis.