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      Naringin Promotes Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells via Wnt/ β-Catenin

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          Abstract

          Purpose

          This investigation intended to unravel the effect and mechanism of naringin on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs).

          Methods

          hDPSCs were induced to differentiate, and the degree of cell differentiation was observed by alizarin red staining, Oil Red O staining, and Alcian blue staining. hDPSCs were treated with 0, 20, 40, and 80  μmol/L naringin for 48 h, respectively. The proliferation rate and chemotaxis of the cells were measured by MTT and transwell assay, alkaline phosphatase (ALP) activity and osteogenic differentiation degree by ALP staining and alizarin red staining, and gene expression of osteogenic markers by qRT-PCR. Additionally, western blot was performed to test the levels of Wnt/ β-catenin signaling-related proteins in hDPSCs.

          Results

          The isolated hDPSCs with spindle-shaped morphology had good differentiation capability. Further experiments confirmed naringin-caused increases in the proliferation rate and migration ability of hDPSCs. In addition, compared with the control group, naringin-treated cells had strong ALP activity and ossification levels and higher expression of Runx2, OPN, DSPP, and DMP1. The western blot results showed that naringin significantly activated Wnt/ β-catenin signaling in hDPSCs.

          Conclusion

          Taken together, naringin enhances the proliferation, migration, and osteogenesis of hDPSCs through stimulating Wnt/ β-catenin signaling pathway.

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          Most cited references33

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          Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

          Dentinal repair in the postnatal organism occurs through the activity of specialized cells, odontoblasts, that are thought to be maintained by an as yet undefined precursor population associated with pulp tissue. In this study, we isolated a clonogenic, rapidly proliferative population of cells from adult human dental pulp. These DPSCs were then compared with human bone marrow stromal cells (BMSCs), known precursors of osteoblasts. Although they share a similar immunophenotype in vitro, functional studies showed that DPSCs produced only sporadic, but densely calcified nodules, and did not form adipocytes, whereas BMSCs routinely calcified throughout the adherent cell layer with clusters of lipid-laden adipocytes. When DPSCs were transplanted into immunocompromised mice, they generated a dentin-like structure lined with human odontoblast-like cells that surrounded a pulp-like interstitial tissue. In contrast, BMSCs formed lamellar bone containing osteocytes and surface-lining osteoblasts, surrounding a fibrous vascular tissue with active hematopoiesis and adipocytes. This study isolates postnatal human DPSCs that have the ability to form a dentin/pulp-like complex.
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            The Wnt signaling pathway in cancer.

            The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.
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              Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells.

              Recently, numerous types of human dental tissue-derived mesenchymal stem cells (MSCs) have been isolated and characterized, including dental pulp stem cells, stem cells from exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor cells, alveolar bone-derived MSCs, stem cells from apical papilla, tooth germ progenitor cells, and gingival MSCs. All these MSC-like cells exhibit self-renewal, multilineage differentiation potential, and immunomodulatory properties. Several studies have demonstrated the potential advantages of dental stem cell-based approaches for regenerative treatments and immunotherapies. This review outlines the properties of various dental MSC-like populations and the progress toward their use in regenerative therapy. Several dental stem cell banks worldwide are also introduced, with a view toward future clinical application.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2022
                29 May 2022
                29 May 2022
                : 2022
                : 4505471
                Affiliations
                1Department of General Dentistry, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
                2The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
                3Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
                4Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
                Author notes

                Academic Editor: Muhammad Zia-Ul-Haq

                Author information
                https://orcid.org/0000-0003-2554-8278
                Article
                10.1155/2022/4505471
                9168102
                35677363
                5a1e987d-7a34-4684-8bc2-5a5523c8d7cd
                Copyright © 2022 Meiling Guo et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 April 2022
                : 11 May 2022
                : 19 May 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81960201
                Funded by: Jiangxi Provincial Department of Science and Technology
                Award ID: 20202BBGL73013
                Funded by: Education Department of Jiangxi Province
                Award ID: GJJ19010
                Award ID: GJJ180162
                Funded by: Health Commission of Jiangxi Province
                Award ID: 202210673
                Funded by: Traditional Chinese Medicine Science and Technology Program of Jiangxi Province
                Award ID: 2021A385
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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