Bone Morphogenetic Protein 7 Promotes the Differentiation of Periodontal Ligament Fibroblasts into F-Spondin-Expressing Cementoblast-like Cells During Root Canal Treatment—An In Vivo Rat Pulpectomy Model and In Vitro Human Fibroblast Study

<b>Background/Objectives:</b> The optimal healing process following root canal treatment involves biological apical sealing through new cementum formation. Bone morphogenetic protein 7 (BMP-7) has recently gained attention as a potential regulator of cementoblast differentiation and periodontal regeneration. However, its effects on periodontal ligament fibroblasts (PDLFs) and the underlying mechanisms remain incompletely understood. This study aimed to investigate whether BMP-7 induces cementoblast-like differentiation of PDLFs both in vivo and in vitro via the BMP-SMAD signaling pathway. <b>Methods:</b> In a rat pulpectomy model, root canals were treated with or without BMP-7 and examined histologically and immunohistochemically for F-spondin (Spon1) expression. In vitro, human PDLFs were stimulated with BMP-7, and analyses of mineralization, cementoblast marker expression, alkaline phosphatase activity, and SMAD-1/5/9 phosphorylation were conducted. <b>Results:</b> Immunohistochemical analysis revealed that Spon1-positive regions increased around the apical area following BMP-7 treatment, suggesting the induction of cementoblast-like differentiation. In vitro, BMP-7 enhanced the expression of cementoblast-associated genes and mineral deposition while activating SMAD-1/5/9 signaling. Phosphorylation was suppressed by the BMP receptor inhibitor LDN-193189, indicating canonical BMP-SMAD pathway involvement. <b>Conclusions:</b> Although the specific concentration range of maximal activity remains to be determined, the findings collectively suggest that BMP-7 can promote cementoblast-like differentiation of PDLFs and may contribute to apical healing through cementum-related mechanisms. These results provide mechanistic and biological insights that support the potential of BMP-7 as a modulator for biologically favorable periapical tissue regeneration following root canal therapy.