Columbianadin promotes osteoblast differentiation by modulating the SIRT1/β-catenin pathway in periodontitis and orthodontic tooth movement-induced rats.

Periodontitis (PD), a common inflammatory disorder causing irreversible periodontal degradation, is linked to systemic issues. Orthodontic tooth movement (OTM) in the context of PD worsens bone loss, which severely compromises orthodontic treatment stability and increases the risk of treatment failure. This study aims to thoroughly investigate the protective effects of Columbianadin (CBN) against PD/OTM-induced alveolar bone injury and dissect its underlying molecular mechanisms. To induce osteogenic differentiation, MC3T3-E1 cells were maintained in a specialized osteogenic induction medium supplemented with ascorbic acid and β-glycerophosphate. In vitro experiments using MC3T3-E1 cells revealed that CBN treatment substantially fostered osteoblastic differentiation, as reflected by elevated alkaline phosphatase (ALP) activity and robust matrix mineralization. Mechanistically, CBN enhanced SIRT1-mediated β-catenin deacetylation, whereas EX527-driven SIRT1 inhibition reduced β-catenin activity in differentiated cells. A rat OTM model within the framework of PD was established to document alveolar bone loss. We found that CBN exerted a protective effect on alveolar bone mass in PD/OTM rats, as it not only promoted alveolar bone formation but also inhibited bone resorption. CBN treatment also suppressed pro-inflammatory cytokine secretion in the alveolar bone of PD/OTM rats. Network pharmacology analysis identified potential target genes involved in CBN-mediated osteogenic differentiation. In summary, CBN protects against PD/OTM-induced alveolar bone damage in a SIRT1/β-catenin-dependent manner, suggesting CBN as a promising candidate for treating periodontal and OTM-related bone disorders.