IL‐33 guides osteogenesis and increases proliferation and pluripotency marker expression in dental stem cells

Abstract

Objectives Soluble IL‐33 (interleukin (IL)‐1‐like cytokine) acts as endogenous alarm signal (alarmin). Since alarmins, besides activating immune system, act to restore tissue homeostasis, we investigated whether IL‐33 exerts beneficial effects on oral stem cell pull. Materials and Methods Clonogenicity, proliferation, differentiation and senescence of stem cells derived from human periodontal ligament (PDLSCs) and dental pulp (DPSCs) were determined after in vitro exposure to IL‐33. Cellular changes were detected by flow cytometry, Western blot, immunocytochemistry and semiquantitative RT‐PCR. Results IL‐33 stimulated proliferation, clonogenicity and expression of pluripotency markers, OCT‐4, SOX‐2 and NANOG, but it inhibited ALP activity and mineralization in both PDLSCs and DPSCs. Higher Ki67 expression and reduced β‐galactosidase activity in IL‐33‐treated cells were demonstrated, whereas these trends were more conspicuous in osteogenic medium. However, after 7‐day IL‐33 pretreatment, differentiation capacity of IL‐33‐pretreated cells was retained, and increased ALP activity was observed in both cell types. Results showed that IL‐33 regulates NF‐κB and β‐catenin signalling, indicating the association of these molecules with changes observed in IL‐33‐treated PDLSCs and DPSCs, particularly their proliferation, pluripotency‐associated marker expression and osteogenesis. Conclusions IL‐33 treatment impairs osteogenesis of PDLSCs and DPSCs, while increases their clonogenicity, proliferation and pluripotency marker expression. After exposure to IL‐33, osteogenic capacity of cells stayed intact. NF‐κB and β‐catenin are implicated in the effects achieved by IL‐33 in PDLSCs and DPSCs.

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

“…Activation of NF- κ B also inhibits osteoblast production. The activation of NF- κ B upregulates miRNA-150-3p, inhibiting osteogenesis of mesenchymal stem cells by encouraging β -catenin degradation [ 111 ]. Besides, NF- κ B has a direct role in inhibiting BMP and Wnt signaling and negatively regulates bone mass through sclerostin [ 112 ].…”

Extracellular IL-37 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the PI3K/AKT signaling pathway

“…Huh et al reported that IL-6 enhanced osteogenic differentiation of stem cells by activating signal transducer and activator of transcription factor 3 15 . In an in vitro study by Kukolj et al, IL‐33 was found to guide osteogenesis in dental stem cells 17 . On the other hand, another important inflammatory cytokine, IL-1β, was found to suppress osteogenesis and adipogenesis of MSCs 18 .…”

Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration

“…TNF- α and IL-6 promote the osteogenic differentiation of DPSCs [ 96 , 97 ]. IL-33 treatment impairs osteogenesis of PDLSCs and DPSCs, while pretreated IL-33 can increase osteogenesis of PDLSCs and DPSCs [ 98 ]. The possible reason is that short-term and low-dose stimulation of IL-33 can promote tissue healing, while long-term and high-dose stimulation of IL-33 can aggravate tissue damage.…”