Nell-1 attenuates lipopolysaccharide-induced inflammation in human dental pulp cells

Cao, Rong-Yu; Wang, Qiang; Wu, Jiameng; Liu, Mengmeng; Han, Qi; Wang, Xiaoying

doi:10.1007/s10735-021-09976-y

Cited by 10 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, we implied that the influence of IWP‐2 on the immunosuppressive characteristics of hDPSCs was mediated through the p38 MAPK and PI3K signalling pathways. Similar to our results, the previous studies reported that the p38 MAPK inhibitor diminished the anti‐inflammatory response of Nel‐like molecule type 1 (Nell‐1) in LPS‐induced pulpitis rat (Cao et al., 2021). However, all inhibitors did not abolish the effect of IWP‐2 on TGFB1 mRNA expression in LPS‐treated hDPSCs.…”

Section: Discussionsupporting

confidence: 92%

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

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

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

Chansaenroj,

Kornsuthisopon,

Suwittayarak

et al. 2023

Int Endodontic J

View full text Add to dashboard Cite

show abstract

“…Nel-like molecule type 1 (Nell-1) is a compound used as an osteoinductive factor. Human recombinant Nell-1 attenuates p38 and ERK MAPK pathways and decreases expression of IL-6 and IL-8 in LPS-stimulated cells [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

et al. 2022

View full text Add to dashboard Cite

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

show abstract

“…13 Accordingly, a recent study found that Nell-1 attenuates lipopolysaccharide (LPS)-induced inflammation in a concentration-dependent manner in vitro. 14 Previous investigations from our group revealed that Nell-1 could modulate the ratio of M2/M1 macrophages in vitro, in particular at a concentration of 200 ng/mL (unpublished data). In addition, Nell-1 is considered as a potential drug candidate in animal models of osteoporosis and osteoarthritis owing to its prochondrogenic effects, promotion of osteoblast differentiation, and inhibition of osteoclast-directed bone resorption, 15,16 supporting a role for Nell-1 in immunity and bone homeostasis.…”

Section: Introductionmentioning

confidence: 85%

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis

Liao,

Ni,

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

The disruption of host–microbe homeostasis and uncontrolled inflammatory response have been considered as vital causes for developing periodontitis, subsequently leading to an imbalance between the bone and immune system and the collapse of bone homeostasis. Consequently, strategies to modulate the immune response and bone metabolization have become a promising approach to prevent and treat periodontitis. In this study, we investigated the cooperative effects of Nel-like molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage polarization, osteoclast differentiation, and the corresponding functions in an experimental model of periodontitis in rats. Nell-1-combined AuNPs in in vitro studies were found to reduce the production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio of M2/M1 macrophages by inducing macrophage polarization into the M2 phenotype, and inhibit cell fusion, maturation, and activity of osteoclasts. Furthermore, the local application of Nell-1-combined AuNPs in in vivo studies resulted in alleviation of damages to the periodontal and bone tissues, modulation of macrophage polarization and the activity of osteoclasts, and alteration of the periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05). These findings reveal that Nell-1-combined AuNPs could be a promising drug candidate for the prevention and treatment of periodontitis. However, Nell-1-combined AuNPs did not show organ toxicity or impair the integrity of intestinal epithelium but alter the gut microbiota, leading to the dysbiosis of gut microbiota. The adverse impact of changes in gut microbiota needs to be further investigated. Nonetheless, this study provides a novel perspective and direction for the biological safety assessment of biomaterials in oral clinical applications.

show abstract

Nell-1 attenuates lipopolysaccharide-induced inflammation in human dental pulp cells

Cited by 10 publications

References 33 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

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis

Contact Info

Product

Resources

About