Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6

Abstract

Periodontal ligament stem cells (PDLSCs) play a significant role on periodontal tissue and alveolar bone homeostasis. During inflammation, 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 inflammation causes periodontium degradation, especially alveolar bone. However, in this study, we show that an inflammatory mediator, IL-6, may serve another direction on alveolar bone homeostasis during inflammatory condition. We found that, IL-6 at 10 and 20 ng/mL was not cytotoxic and dose-dependently exerted beneficial effects on osteogenic differentiation of human PDLSCs (hPDLSCs), as demonstrated by increased alkaline phosphatase activity, mRNA expression of osteogenic markers, and matrix mineralization. The presence of physiological and inflammatory level of IL-6, the osteogenic differentiation 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 differentiation 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 different mechanisms. Further validation by gene silencing, treatment with recombinant Wnt ligands, and β-catenin stabilization/translocation confirmed 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 findings fulfill the homeostasis pathway governing periodontal tissue and alveolar bone regeneration and may serve for further therapeutic regimen design for restoring the tissues.

MicroRNA expression in JAG1/Notch-activated periodontal ligament stem cells

“…The Wnt signaling pathway a signal transduction pathway is also known to be crucial for osteogenic differentiation and bone formation in MSCs, playing a role in periodontal homeostasis, pathological process, and tissue regeneration [ 41 ]. In hPDLSCs, Wnt signaling pathway served as a key regulator of osteogenic differentiation [ 42 ]. Our results reiterate the importance of miRNA regulation of these pathways in controlling osteogenesis associated with periodontal regeneration.…”

Interaction between immuno-stem dual lineages in jaw bone formation and injury repair

“…IL-35 also can reduce jaw loss by modulating the Th17/Treg balance and reducing the RANKL/OPG ratio ( CAFFERATA et al, 2020 ; LI S. et al, 2023 ). In addition, a certain IL-6 dose can increase APL activity and the mRNA expression of osteogenic markers and promote osteogenic differentiation of PDLSCs ( PURWANINGRUM et al, 2023 ). IL-6 activates the STAT3 signaling pathway, a critical signaling pathway for bone reconstruction, to promote the osteogenic differentiation of MSCs ( XIE et al, 2018 ).…”

“…Macrophages are an important source of Wnt ligands during inflammation and healing, and T cells produce Wnt10b ( WEITZMANN, 2017 ). IL-6 derived from immune cells mediates the osteogenic differentiation of hPDLSCs via the Wnt signaling pathway ( PURWANINGRUM et al, 2023 ). In the presence of lithium chloride (a Wnt activator), macrophages are recruited to periodontal defect sites.…”

Trends of regenerative tissue engineering for oral and maxillofacial reconstruction in veterinary medicine

“…Stem cells have also been isolated from the oral tissues of non-human mammalian species including canines, felines, equines, chimpanzees, swines, murines, and minipigs (34,43,(50)(51)(52)(53). Among these, canine-derived oral-origin MSCs have been widely studied (41,43,(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64). In contrast, feline-derived oral-origin MSCs have only been sparsely reported.…”