Berberine mediates root remodeling in an immature tooth with apical periodontitis by regulating stem cells from apical papilla differentiation

Abstract

Once pulp necrosis or apical periodontitis occurs on immature teeth, the weak root and open root apex are challenging to clinicians. Berberine (BBR) is a potential medicine for bone disorders, therefore, we proposed to apply BBR in root canals to enhance root repair in immature teeth. An in vivo model of immature teeth with apical periodontitis was established in rats, and root canals were filled with BBR, calcium hydroxide or sterilized saline for 3 weeks. The shape of the roots was analyzed by micro-computed tomography and histological staining. In vitro, BBR was introduced into stem cells from apical papilla (SCAPs). Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity, mineralization ability, and gene expression of osteogenic makers. The signaling pathway, which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR, Western blot analysis, and immunofluorescence. In rats treated with BBR, more tissue was formed, with longer roots, thicker root walls, and smaller apex diameters. In addition, we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent manner. BBR induced the expression of β-catenin and enhanced β-catenin entering into the nucleus, to up-regulate more runt-related nuclear factor 2 downstream. BBR enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.

Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement

“…Berberine was also found to be responsible for inducing the β-catenin expression and enhancing β-catenin entry in the nucleus, upregulating nuclear factor 2 downstream. Root repair enhancement in the case of immature teeth with apical periodontitis by the activation of β-catenin and canonical Wnt pathway in SCAPs was also reported in this study [ 188 ]. Similarly, berberine was also reported to increase the cell proliferation of DPSCs in a dose-dependent manner and promote dexamethasone-induced osteogenic differentiation via enhancement of Runx2 transcription factor activity that was followed by upregulation of osteogenesis marker expression.…”

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

“…In addition, the secretion of crimp-related protein I (sFRP1) is involved in the osteogenic differentiation of HPLCs under inflammatory conditions by antagonizing Wnt (Yang F et al, 2021). Both the promotion of bone repair by berberine and the role of Dickkopf-1 in mediating bone damage are associated with the regulation of the Wnt/b-catenin signaling pathway (Tan et al, 2018;Cui et al, 2020).…”

Unraveling the Role of the Apical Papilla During Dental Root Maturation

“…Strategies are currently being investigated to restore or regenerate defective root formation. Berberine has been shown to induce root repair via activation of the Wnt/β-catenin pathway in SCAP leading to longer roots and thicker root walls ( Cui et al, 2020 ). Mixture of SCAP and PDLSCs has proven to initiate regeneration of the root and periodontal structure in swine ( Sonoyama et al, 2006 ).…”