Dissecting specifc Wnt components governing osteogenic diferentiation potential by humanperiodontal ligament stem cells through interleukin‑6

Periodontal ligament stem cells (PDLSCs) play a signifcant role on periodontal tissue and alveolar bone homeostasis. During infammation, interleukin (IL)-6 serves as one of key cytokine players controlling tissue reaction as well as alveolar bone tissue remodeling. It is believed that periodontal tissue infammation causes periodontium degradation, especially alveolar bone. However, in this
study, we show that an infammatory mediator, IL-6, may serve another direction on alveolar bone homeostasis during infammatory condition. We found that, IL-6 at 10 and 20 ng/mL was not cytotoxic and dose-dependently exerted benefcial efects on osteogenic diferentiation of human
PDLSCs (hPDLSCs), as demonstrated by increased alkaline phosphatase activity, mRNA expression of osteogenic markers, and matrix mineralization. The presence of physiological and infammatory level of IL-6, the osteogenic diferentiation potential by hPDLSCs was enhanced by several possible
mechanisms including transforming growth factor (TGF), Wnt, and Notch pathways. After in-depth and thorough exploration, we found that Wnt pathway serves as key regulator controlling osteogenic diferentiation by hPDLSCs amid the IL-6 presentation. Surprisingly, apart from other mesenchymal stem cells, distinct Wnt components are employed by hPDLSCs, and both canonical and non-canonical
Wnt pathways are triggered by diferent mechanisms. Further validation by gene silencing, treatment with recombinant Wnt ligands, and β-catenin stabilization/translocation confrmed that IL-6 governed the canonical Wnt/β-catenin pathway via either WNT2B or WNT10B and employed WNT5A to activate
the non-canonical Wnt pathway. These fndings fulfll the homeostasis pathway governing periodontal tissue and alveolar bone regeneration and may serve for further therapeutic regimen design for restoring the tissues.