Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration
Abstract Background Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03353-0 |
| _version_ | 1827943525939937280 |
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| author | Zijie Wang Chuying Chen Jiayi Zhang Jiangdie He Lin Zhang Jiayuan Wu Zhihui Tian |
| author_facet | Zijie Wang Chuying Chen Jiayi Zhang Jiangdie He Lin Zhang Jiayuan Wu Zhihui Tian |
| author_sort | Zijie Wang |
| collection | DOAJ |
| description | Abstract Background Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium–mesenchyme interactions. Methods Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp–dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests. Results The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance. Conclusion SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration. |
| first_indexed | 2024-03-13T10:16:45Z |
| format | Article |
| id | doaj.art-6cf6b46c784949ddb65ca94d1742cc5e |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-13T10:16:45Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-6cf6b46c784949ddb65ca94d1742cc5e2023-05-21T11:10:22ZengBMCStem Cell Research & Therapy1757-65122023-05-0114111610.1186/s13287-023-03353-0Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regenerationZijie Wang0Chuying Chen1Jiayi Zhang2Jiangdie He3Lin Zhang4Jiayuan Wu5Zhihui Tian6Department of Stomatology, Nanfang Hospital, Southern Medical UniversityDepartment of Stomatology, Nanfang Hospital, Southern Medical UniversityDepartment of Stomatology, Nanfang Hospital, Southern Medical UniversityDepartment of Stomatology, Nanfang Hospital, Southern Medical UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Southern Medical UniversityHospital of Stomatology, Zunyi Medical UniversityDepartment of Stomatology, Nanfang Hospital, Southern Medical UniversityAbstract Background Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium–mesenchyme interactions. Methods Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp–dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests. Results The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance. Conclusion SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration.https://doi.org/10.1186/s13287-023-03353-0SCUBE3Pulp–dentin regenerationOdontoblastic differentiationBMP2/Smad signallingTGF/Smad signallingParacrine/autocrine |
| spellingShingle | Zijie Wang Chuying Chen Jiayi Zhang Jiangdie He Lin Zhang Jiayuan Wu Zhihui Tian Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration Stem Cell Research & Therapy SCUBE3 Pulp–dentin regeneration Odontoblastic differentiation BMP2/Smad signalling TGF/Smad signalling Paracrine/autocrine |
| title | Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| title_full | Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| title_fullStr | Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| title_full_unstemmed | Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| title_short | Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| title_sort | epithelium derived scube3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration |
| topic | SCUBE3 Pulp–dentin regeneration Odontoblastic differentiation BMP2/Smad signalling TGF/Smad signalling Paracrine/autocrine |
| url | https://doi.org/10.1186/s13287-023-03353-0 |
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