Non-canonical Wnt signaling participates in Jagged1-induced osteo/odontogenic differentiation in human dental pulp stem cells

Kornsuthisopon, Chatvadee; Chansaenroj, Ajjima; Manokawinchoke, Jeeranan; Tompkins, Kevin; Pirarat, Nopadon; Osathanon, Thanaphum

doi:10.1038/s41598-022-11596-9

Cited by 11 publications

(5 citation statements)

References 54 publications

(67 reference statements)

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“…The previous report demonstrated that IWP‐2 at 25 μM effectively blocked Wnt pathway and was able to inhibit Jagged1‐induced mineralization in hDPSCs (Kornsuthisopon, Chansaenroj, et al., 2022). We varied the IWP‐2 concentration and performed the MTT assay to assess cell viability and proliferation.…”

Section: Resultsmentioning

confidence: 95%

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

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AimTo investigate the effect of IWP‐2, Wnt inhibitor, on human dental pulp stem cells (hDPSCs) responses.MethodologyhDPSCs were isolated from human dental pulp tissues. Cells were treated with 25 μM IWP‐2 for 24 h, and subsequently, the gene expression profile was examined using high‐throughput RNA sequencing. The mRNA expression was analysed using qPCR. The effect of IWP‐2 was investigated in both normal and LPS‐induced hDPSCs (inflamed hDPSCs). CD4+ T cells and CD14+ monocyte‐derived macrophages were cultured with conditioned media of IWP‐2 treated hDPSCs to observe the immunosuppressive property.ResultsRNA sequencing indicated that IWP‐2 significantly downregulated several KEGG pathways, including cytokine‐cytokine receptor interaction, IL‐17 signalling pathway, and TNF signalling pathway. In both normal and inflamed conditions, IWP‐2 markedly upregulated TGFB1 mRNA expression while the mRNA expression of pro‐inflammatory cytokines, TNFA, IL1B, IFNG, and IL6, was inhibited. In the inhibition experiment, the pretreatment with p38, MAPK, or PI3K inhibitors abolished the effects of IWP‐2 in LPS‐induced inflammation. In terms of immune cells, IWP‐2‐treated‐inflamed hDPSCs conditioned media attenuated T cell proliferation and regulated regulatory T cell differentiation. In addition, the migratory property of macrophage was decreased after being exposed to IWP‐2‐treated inflamed hDPSCs conditioned media.ConclusionIWP‐2 suppressed inflammatory cytokine expression in both normal and inflamed hDPSCs. Moreover, hDPSCs exerted the immunosuppressive property after IWP‐2 treatment. These results suggest the role of Wnt in inflammatory responses and immunomodulation in dental pulp tissues.

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Section: Resultsmentioning

confidence: 95%

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

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“…We and others have previously demonstrated that JAG1 exhibits osteo-inductive properties in murine cell lines (1,37,(42)(43)(44). JAG1 also induces the expression of pre-osteoblast genes like Runx2 in murine CNC cells, even when the canonical NOTCH pathway is disabled using DAPT (1,28), and further promotes CNC cell commitment to osteoblast differentiation via a JAG1-JAK2 non-canonical signaling pathway (1,43).…”

Section: Discussionmentioning

confidence: 91%

Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects

Kamalakar,

Tobin,

Kaimari

et al. 2023

Preprint

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Treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and expensive. Current reconstructive methods include surgical correction of injuries, short-term bone stabilization, and long-term use of bone grafting solutions, including implantation of (i) allografts which are prone to implant failure or infection, (ii) autografts which are limited in supply. Current bone regenerative approaches have consistently relied on BMP-2 application with or without addition of stem cells. BMP2 treatment can lead to severe bony overgrowth or uncontrolled inflammation, which can accelerate further bone loss. Bone marrow-derived mesenchymal stem cell-based treatments, which do not have the side effects of BMP2, are not currently FDA approved, and are time and resource intensive. There is a critical need for novel bone regenerative therapies to treat CF bone loss that have minimal side effects, are easily available, and are affordable. In this study we investigated novel bone regenerative therapies downstream of JAGGED1 (JAG1).We previously demonstrated that JAG1 induces murine cranial neural crest (CNC) cells towards osteoblast commitment via a NOTCH non-canonical pathway involving JAK2-STAT5 (1) and that JAG1 delivery with CNC cells elicits bone regenerationin vivo.In this study, we hypothesized that delivery of JAG1 and induction of its downstream NOTCH non-canonical signaling inpediatric human osteoblastsconstitute an effective bone regenerative treatment in anin vivomurine bone loss model of a critically-sized cranial defect. Using this CF defect modelin vivo, we delivered JAG1 with pediatric human bone-derived osteoblast-like (HBO) cells to demonstrate the osteo-inductive properties of JAG1 in human cells andin vitrowe utilized the HBO cells to identify the downstream non-canonical JAG1 signaling intermediates as effective bone regenerative treatments.In vitro,we identified an important mechanism by which JAG1 induces pediatric osteoblast commitment and bone formation involving the phosphorylation of p70 S6K. This discovery enables potential new treatment avenues involving the delivery of tethered JAG1 and the downstream activators of p70 S6K as powerful bone regenerative therapies in pediatric CF bone loss.

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“…WNT5A and WNT5B, major Wnt proteins found in non-canonical Wnt signaling, have been reported for their ability to enhance osteogenic differentiation in www.nature.com/scientificreports/ several cells 26 . Crosstalk between Notch and Wnt signaling through WNT5A regulated the osteo/odontogenic differentiation of DPSCs 27 . WNT5B is involved in osteoblast differentiation in human BMSCs induced by phosphate 28 .…”

Section: Discussionmentioning

confidence: 99%

Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways

Kornsuthisopon,

Nowwarote,

Chansaenroj

et al. 2024

Sci Rep

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Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.

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Non-canonical Wnt signaling participates in Jagged1-induced osteo/odontogenic differentiation in human dental pulp stem cells

Cited by 11 publications

References 54 publications

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

IWP‐2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro

Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects

Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways

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