Effects of ECM Components on Periodontal Ligament Stem Cell Differentiation Under Conditions of Disruption of Wnt and TGF-β Signaling Pathways

Periodontitis is accompanied by inflammation that causes dysregulation of the Wnt/β-catenin and TGF-β signaling pathways. This leads to a violation of the homeostasis of periodontal tissues. Components of the extracellular matrix (ECM) are an important part of biomaterials used for the repair of periodontal tissue. The purpose of this study was to evaluate the components of the effect of ECM (hyaluronic acid (HA), fibronectin (Fn), and laminin (Lam)) on the osteogenic and odontogenic differentiation of periodontal ligament stem cells (PDLSCs) in the collagen I hydrogel under conditions of disruption of the Wnt/β-catenin and TGF-β signaling pathways. The study showed that the addition of components of the ECM restored the expression of odontogenic markers in PDLSCs, which was absent during inhibition of the canonical Wnt signaling pathway, and their multidirectional effect on the secretion of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2). Fn and Lam suppressed the expression of odontogenic markers in PDLSCs against the background of inhibition of the TGF-β signaling pathway. The addition of HA under the conditions of the TGF-β signaling pathway improved BMP-2 secretion, preserving odontogenic differentiation. Thus, our results demonstrated that disruption of the Wnt/β-catenin and TGF-β signaling pathways causes disorders in the differentiation of PDLSCs, preventing the regeneration of periodontal tissues. This should be taken into account when developing multicomponent scaffolds that recapitulate the ECM microenvironment at endogenic regeneration of the periodontium. Inclusion of hyaluronic acid as one of these components may enhance the therapeutic effect of such biomaterials.