Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny
)Abstract
Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig’s epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
References
Cicalău, G. I. P. et al. Anti-inflammatory and antioxidant properties of carvacrol and magnolol, in periodontal disease and diabetes mellitus. Molecules https://doi.org/10.3390/molecules26226899 (2021).
Friedlander, L., Berdal, A., Cormier-Daire, V., Lyonnet, S. & Garcelon, N. Determinants of dental care use in patients with rare diseases: a qualitative exploration. BMC Oral. Health 23, 413 (2023).
Sahingur, S. E. & Yeudall, W. A. Chemokine function in periodontal disease and oral cavity cancer. Front. Immunol. 6, 214 (2015).
Ostrovidov, S. et al. Bioprinting and biomaterials for dental alveolar tissue regeneration. Front. Bioeng. Biotechnol. 11, 991821 (2023).
Safi, I. N., Hussein, B. M. A. & Al-Shammari, A. M. Bio-hybrid dental implants prepared using stem cells with β-TCP-coated titanium and zirconia. J. Periodontal. Implant Sci. 52, 242–257 (2022).
An, Y. Z., Heo, Y. K., Lee, J. S., Jung, U. W. & Choi, S. H. Dehydrothermally cross-linked collagen membrane with a bone graft improves bone regeneration in a rat calvarial defect model. Materials https://doi.org/10.3390/ma10080927 (2017).
Busenlechner, D. et al. Long-term implant success at the Academy for Oral Implantology: 8-year follow-up and risk factor analysis. J. Periodontal. Implant Sci. 44, 102–108 (2014).
Volponi, A. A., Pang, Y. & Sharpe, P. T. Stem cell-based biological tooth repair and regeneration. Trends Cell Biol. 20, 715–722 (2010).
Jamal, H. A. Tooth organ bioengineering: cell sources and innovative approaches. Dent. J. https://doi.org/10.3390/dj4020018 (2016).
Jussila, M. & Thesleff, I. Signaling networks regulating tooth organogenesis and regeneration, and the specification of dental mesenchymal and epithelial cell lineages. Cold Spring Harb. Perspect. Biol. 4, a008425 (2012).
Boy, S., Crossley, D. & Steenkamp, G. Developmental structural tooth defects in dogs - experience from veterinary dental referral practice and review of the literature. Front. Vet. Sci. 3, 9 (2016).
Liu, Z. & Lian, W. Molecular mechanisms of bone morphogenetic protein, Wnt, fibroblast growth factor and sonic hedgehog signaling pathways in tooth development. Chin. J. Tissue Eng. Res. 22, 5897 (2018).
Zhang, W., Ju, J. & Gronowicz, G. Odontoblast-targeted Bcl-2 overexpression impairs dentin formation. J. Cell. Biochem. 111, 425–432 (2010).
Zhang, R. et al. Odontoblast β-catenin signaling regulates fenestration of mouse Hertwig’s epithelial root sheath. Sci. China Life Sci. 58, 876–881 (2015).
Li, J., Parada, C. & Chai, Y. Cellular and molecular mechanisms of tooth root development. Development 144, 374–384 (2017).
Kimura, M. et al. The concurrent stimulation of Wnt and FGF8 signaling induce differentiation of dental mesenchymal cells into odontoblast-like cells. Med. Mol. Morphol. 55, 8–19 (2022).
Jing, J. et al. Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis. Nat. Commun. 13, 4803 (2022).
Yang, C., Du, X. Y. & Luo, W. Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases. World J. Stem Cells 15, 136–149 (2023).
Omi, M. & Mishina, Y. Roles of osteoclasts in alveolar bone remodeling. Genesis 60, e23490 (2022).
Liu, M., Goldman, G., MacDougall, M. & Chen, S. BMP Signaling pathway in dentin development and diseases. Cells https://doi.org/10.3390/cells11142216 (2022).
Sui, B. D. et al. Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis. Physiol. Rev. 103, 1899–1964 (2023).
Ono, W., Sakagami, N., Nishimori, S., Ono, N. & Kronenberg, H. M. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation. Nat. Commun. 7, 11277 (2016).
Hermans, F., Hemeryck, L., Lambrichts, I., Bronckaers, A. & Vankelecom, H. Intertwined signaling pathways governing tooth development: a give-and-take between canonical Wnt and Shh. Front. Cell Dev. Biol. 9, 758203 (2021).
Wakao, S., Kuroda, Y., Ogura, F., Shigemoto, T. & Dezawa, M. Regenerative effects of mesenchymal stem cells: contribution of muse cells, a novel pluripotent stem cell type that resides in mesenchymal cells. Cells 1, 1045–1060 (2012).
Ibarretxe, G. et al. Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells Int 2012, 103503 (2012).
Nagata, M., Ono, N. & Ono, W. Unveiling diversity of stem cells in dental pulp and apical papilla using mouse genetic models: a literature review. Cell Tissue Res. 383, 603–616 (2021).
Kumakami-Sakano, M., Otsu, K., Fujiwara, N. & Harada, H. Regulatory mechanisms of Hertwig׳s epithelial root sheath formation and anomaly correlated with root length. Exp. Cell Res. 325, 78–82 (2014).
Bousnaki, M., Beketova, A. & Kontonasaki, E. A review of in vivo and clinical studies applying scaffolds and cell sheet technology for periodontal ligament regeneration. Biomolecules https://doi.org/10.3390/biom12030435 (2022).
Liu, Y. et al. An Nfic-hedgehog signaling cascade regulates tooth root development. Development 142, 3374–3382 (2015).
Arai, C. et al. Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains. Sci. Rep. 7, 45181 (2017).
Phattarataratip, E. et al. Expression of SOX2 and OCT4 in odontogenic cysts and tumors. Head Face Med. (2021).
Juuri, E. et al. Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors. Dev. Cell 23, 317–328 (2012).
Li, J. et al. BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth. Dev. Cell 33, 125–135 (2015).
Yu, T. & Klein, O. D. Molecular and cellular mechanisms of tooth development, homeostasis and repair. Development https://doi.org/10.1242/dev.184754 (2020).
Guo, Y. et al. Comparative study on differentiation of cervical-loop cells and Hertwig’s epithelial root sheath cells under the induction of dental follicle cells in rat. Sci. Rep. 8, 6546 (2018).
Azumane, M. et al. Semaphorin-RhoA signaling regulates HERS maintenance by acting against TGF-β-induced EMT. J. Periodontal. Res. 58, 184–194 (2023).
Bi, F. et al. Hertwig’s epithelial root sheath cells show potential for periodontal complex regeneration. J. Periodontol. 94, 263–276 (2023).
Hosoya, A., Shalehin, N., Takebe, H., Shimo, T. & Irie, K. Sonic hedgehog signaling and tooth development. Int. J. Mol. Sci. https://doi.org/10.3390/ijms21051587 (2020).
Thanaruengrong, P., Kulvitit, S., Navachinda, M. & Charoenlarp, P. Prevalence of complex root canal morphology in the mandibular first and second premolars in Thai population: CBCT analysis. BMC Oral. Health 21, 449 (2021).
Guo, H. et al. Development and regeneration of periodontal supporting tissues. Genesis 60, e23491 (2022).
Jheon, A. H., Seidel, K., Biehs, B. & Klein, O. D. From molecules to mastication: the development and evolution of teeth. Wiley Interdiscip. Rev. Dev. Biol. 2, 165–182 (2013).
Li, X. et al. Development of immortalized Hertwig’s epithelial root sheath cell lines for cementum and dentin regeneration. Stem Cell Res Ther. 10, 3 (2019).
Xiao, L. & Dudley, A. C. Fine-tuning vascular fate during endothelial-mesenchymal transition. J. Pathol. 241, 25–35 (2017).
Yamamoto, T. et al. Hertwig’s epithelial root sheath fate during initial cellular cementogenesis in rat molars. Acta Histochem. Cytochem. 48, 95–101 (2015).
Luan, X., Ito, Y. & Diekwisch, T. G. Evolution and development of Hertwig’s epithelial root sheath. Dev. Dyn. 235, 1167–1180 (2006).
Yamamoto, T., Hasegawa, T., Yamamoto, T., Hongo, H. & Amizuka, N. Histology of human cementum: Its structure, function, and development. Jpn Dent. Sci. Rev. 52, 63–74 (2016).
Bosshardt, D. D., Stadlinger, B. & Terheyden, H. Cell-to-cell communication–periodontal regeneration. Clin. Oral. Implants Res. 26, 229–239 (2015).
Foster, B. L. Methods for studying tooth root cementum by light microscopy. Int. J. Oral. Sci. 4, 119–128 (2012).
Pérez-Barbería, F. J. et al. What do rates of deposition of dental cementum tell us? Functional and evolutionary hypotheses in red deer. PLoS ONE 15, e0231957 (2020).
Zhou, T. et al. Dental follicle cells: roles in development and beyond. Stem Cells Int. 2019, 9159605 (2019).
Bertin, T. J. C., Thivichon-Prince, B., LeBlanc, A. R. H., Caldwell, M. W. & Viriot, L. Current perspectives on tooth implantation, attachment, and replacement in amniota. Front. Physiol. 9, 1630 (2018).
Al-Shahrani, Z. M., Balan, U., Assiri, K. I. & Al Qarni, A. M. M. Monoradicular primary mandibular first molar: a rare case in Aseer Province of Saudi Arabia. J. Oral. Maxillofac. Pathol. 24, S120–s123 (2020).
Luder, H. U. Malformations of the tooth root in humans. Front. Physiol. 6, 307 (2015).
Black, N. & Chai Y. Current understanding of the regulatory mechanism of tooth root development and future perspectives. J. Calif. Dent. Assoc. https://doi.org/10.1080/19424396.2023.2194560 (2023).
Yamamoto, H. et al. Developmental properties of the Hertwig’s epithelial root sheath in mice. J. Dent. Res. 83, 688–692 (2004).
Mu, H. et al. Epithelial bone morphogenic protein 2 and 4 are indispensable for tooth development. Front. Physiol. 12, 660644 (2021).
Hosoya, A., Kim, J. Y., Cho, S. W. & Jung, H. S. BMP4 signaling regulates formation of Hertwig’s epithelial root sheath during tooth root development. Cell Tissue Res. 333, 503–509 (2008).
Graf, D., Malik, Z., Hayano, S. & Mishina, Y. Common mechanisms in development and disease: BMP signaling in craniofacial development. Cytokine Growth Factor Rev. 27, 129–139 (2016).
Huang, X., Xu, X., Bringas, P., Hung, Y. P. Jr. & Chai, Y. Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development. J. Bone Miner. Res. 25, 1167–1178 (2010).
Yang, S. et al. Cell dynamics in Hertwig’s epithelial root sheath are regulated by β-catenin activity during tooth root development. J. Cell Physiol. 236, 5387–5398 (2021).
Kim, T. H. et al. β-catenin is required in odontoblasts for tooth root formation. J. Dent. Res. 92, 215–221 (2013).
Yu, M. et al. Epithelial Wnt10a is essential for tooth root furcation morphogenesis. J. Dent. Res. 99, 311–319 (2020).
Chen, J. et al. TGF-β1 and FGF2 stimulate the epithelial-mesenchymal transition of HERS cells through a MEK-dependent mechanism. J. Cell. Physiol. 229, 1647–1659 (2014).
Yang, G. et al. Mesenchymal TGF-β signaling orchestrates dental epithelial stem cell homeostasis through Wnt signaling. Stem Cells 32, 2939–2948 (2014).
Lee, J. H. et al. Dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and Hertwig’s epithelial root sheath/epithelial rests of Malassez cells through the Fas-Fas ligand pathway. Eur. J. Oral. Sci. 120, 29–37 (2012).
Fons Romero, J. M. et al. The impact of the eda pathway on tooth root development. J. Dent. Res. 96, 1290–1297 (2017).
Amato, M., Santonocito, S., Viglianisi, G., Tatullo, M. & Isola, G. Impact of oral mesenchymal stem cells applications as a promising therapeutic target in the therapy of periodontal disease. Int. J. Mol. Sci. https://doi.org/10.3390/ijms232113419 (2022).
Zhang, W. et al. Proliferation and odontogenic differentiation of BMP2 gene‑transfected stem cells from human tooth apical papilla: an in vitro study. Int. J. Mol. Med. 34, 1004–1012 (2014).
Li, G. et al. Local injection of allogeneic stem cells from apical papilla enhanced periodontal tissue regeneration in minipig model of periodontitis. Biomed. Res. Int. 2018, 3960798 (2018).
Driesen, R. B., Gervois, P., Vangansewinkel, T. & Lambrichts, I. Unraveling the role of the apical papilla during dental root maturation. Front. Cell Dev. Biol. 9, 665600 (2021).
Diao, S. et al. Analysis of gene expression profiles between apical papilla tissues, stem cells from apical papilla and cell sheet to identify the key modulators in MSCs niche. Cell Prolif. https://doi.org/10.1111/cpr.12337 (2017).
He, W. et al. Regulatory interplay between NFIC and TGF-β1 in apical papilla-derived stem cells. J. Dent. Res. 93, 496–501 (2014).
Chang, H. H. et al. Role of ALK5/Smad2/3 and MEK1/ERK signaling in transforming growth factor Beta 1-modulated growth, collagen turnover, and differentiation of stem cells from apical papilla of human tooth. J. Endod. 41, 1272–1280 (2015).
Zhang, R. et al. Disruption of Wnt/β-catenin signaling in odontoblasts and cementoblasts arrests tooth root development in postnatal mouse teeth. Int. J. Biol. Sci. 9, 228–236 (2013).
Wang, J., Liu, B., Gu, S. & Liang, J. Effects of Wnt/β-catenin signalling on proliferation and differentiation of apical papilla stem cells. Cell Prolif. 45, 121–131 (2012).
Zhang, H. et al. Canonical Wnt signaling acts synergistically on BMP9-induced osteo/odontoblastic differentiation of stem cells of dental apical papilla (SCAPs). Biomaterials 39, 145–154 (2015).
Chen, T. et al. Inhibition of Ape1 redox activity promotes odonto/osteogenic differentiation of dental papilla cells. Sci. Rep. 5, 17483 (2015).
Yu, G. et al. Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo-/dentinogenic differentiation of stem cells of the apical papilla. Cell Prolif. 49, 330–340 (2016).
Jin, L. et al. SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway. Cell Mol. Biol. Lett. 22, 14 (2017).
He, J. et al. Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning. PLoS Genet. 17, e1009320 (2021).
Ma, Y. et al. Ror2-mediated non-canonical Wnt signaling regulates Cdc42 and cell proliferation during tooth root development. Development https://doi.org/10.1242/dev.196360 (2021).
Bae, C. H. et al. Excessive Wnt/β-catenin signaling disturbs tooth-root formation. J. Periodontal. Res. 48, 405–410 (2013).
Li, J. et al. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development 138, 1977–1989 (2011).
Wen, Q. et al. Runx2 regulates mouse tooth root development via activation of WNT inhibitor NOTUM. J. Bone Miner. Res. 35, 2252–2264 (2020).
Du, J. et al. Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors. Cell Rep. 35, 108964 (2021).
Jing, J. et al. Antagonistic interaction between Ezh2 and Arid1a coordinates root patterning and development via Cdkn2a in mouse molars. Elife https://doi.org/10.7554/eLife.46426 (2019).
Chang, M. C. et al. bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling. J. Adv. Res. 40, 95–107 (2022).
Wu, J. et al. Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. J. Endod. 38, 614–622 (2012).
Cao, Y. et al. Epiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways. Cell Prolif. 46, 447–456 (2013).
Li, Z. et al. LncRNA H19 promotes the committed differentiation of stem cells from apical papilla via miR-141/SPAG9 pathway. Cell Death Dis. 10, 130 (2019).
Li, Y. et al. 17beta-estradiol promotes the odonto/osteogenic differentiation of stem cells from apical papilla via mitogen-activated protein kinase pathway. Stem Cell Res. Ther. 5, 125 (2014).
Wang, Y. et al. Oestrogen receptor α regulates the odonto/osteogenic differentiation of stem cells from apical papilla via ERK and JNK MAPK pathways. Cell Prolif. 51, e12485 (2018).
Wang, L. et al. KDM1A regulated the osteo/dentinogenic differentiation process of the stem cells of the apical papilla via binding with PLOD2. Cell Prolif. 51, e12459 (2018).
Tanaka, Y. et al. Suppression of AKT-mTOR signal pathway enhances osteogenic/dentinogenic capacity of stem cells from apical papilla. Stem Cell Res. Ther. 9, 334 (2018).
Mohamed, F. F., Ge, C., Binrayes, A. & Franceschi, R. T. The role of discoidin domain receptor 2 in tooth development. J. Dent. Res. 99, 214–222 (2020).
Liu, Z., Lin, Y., Fang, X., Yang, J. & Chen Z. Epigallocatechin-3-gallate promotes osteo-/odontogenic differentiation of stem cells from the apical papilla through activating the bmp-smad signaling pathway. Molecules https://doi.org/10.3390/molecules26061580 (2021).
Li, N. et al. PD-1 suppresses the osteogenic and odontogenic differentiation of stem cells from dental apical papilla via targeting SHP2/NF-κB axis. Stem Cells 40, 763–777 (2022).
Wang, N. et al. PRMT6/LMNA/CXCL12 signaling pathway regulated the osteo/odontogenic differentiation ability in dental stem cells isolated from apical papilla. Cell Tissue Res. 389, 187–199 (2022).
Shi, Y. et al. A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development. Cell Biosci. 11, 178 (2021).
Diederic, A. et al. Influence of ascorbic acid as a growth and differentiation factor on dental stem cells used in regenerative endodontic therapies. J. Clin. Med. https://doi.org/10.3390/jcm12031196 (2023).
Tatullo, M. et al. Potential use of human periapical cyst-mesenchymal stem cells (hPCy-MSCs) as a novel stem cell source for regenerative medicine applications. Front. Cell Dev. Biol. 5, 103 (2017).
Guo, L. et al. Comparison of odontogenic differentiation of human dental follicle cells and human dental papilla cells. PLoS ONE 8, e62332 (2013).
Yang, Y. et al. Hertwig’s epithelial root sheath cells regulate osteogenic differentiation of dental follicle cells through the Wnt pathway. Bone 63, 158–165 (2014).
Zhang, X. et al. Dickkopf-related protein 3 negatively regulates the osteogenic differentiation of rat dental follicle cells. Mol. Med. Rep. 15, 1673–1681 (2017).
Chen, C., Zhang, J., Ling, J., Du, Y. & Hou, Y. Nkd2 promotes the differentiation of dental follicle stem/progenitor cells into osteoblasts. Int. J. Mol. Med 42, 2403–2414 (2018).
Viale-Bouroncle, S., Klingelhöffer, C., Ettl, T. & Morsczeck, C. The AKT signaling pathway sustains the osteogenic differentiation in human dental follicle cells. Mol. Cell. Biochem. 406, 199–204 (2015).
Silvério, K. G. et al. Wnt/β-catenin pathway regulates bone morphogenetic protein (BMP2)-mediated differentiation of dental follicle cells. J. Periodontal. Res. 47, 309–319 (2012).
Viale-Bouroncle, S., Klingelhöffer, C., Ettl, T., Reichert, T. E. & Morsczeck, C. A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs). Cell Signal. 27, 598–605 (2015).
Sakisaka, Y. et al. Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells. Exp. Cell Res. 336, 85–93 (2015).
Nemoto, E. et al. Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway. J. Periodontal. Res. 51, 164–174 (2016).
Sakisaka, Y. et al. p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3β signaling axis in dental follicle cells. Biochem. Biophys. Res. Commun. 478, 527–532 (2016).
Gopinathan, G., Foyle, D., Luan, X. & Diekwisch, T. G. H. The Wnt antagonist SFRP1: a key regulator of periodontal mineral homeostasis. Stem Cells Dev. 28, 1004–1014 (2019).
Deng, L. et al. Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway. Biochem. Biophys. Res. Commun. 503, 2061–2067 (2018).
Takahashi, A. et al. Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption. Proc. Natl Acad. Sci. USA 116, 575–580 (2019).
Cui, C. et al. Role of PTH1R signaling in Prx1(+) mesenchymal progenitors during eruption. J. Dent. Res 99, 1296–1305 (2020).
Liu, C., Li, Q., Xiao, Q., Gong, P. & Kang, N. CHD7 regulates osteogenic differentiation of human dental follicle cells via PTH1R signaling. Stem Cells Int. 2020, 8882857 (2020).
Aonuma, H. et al. Characteristics and osteogenic differentiation of stem/progenitor cells in the human dental follicle analyzed by gene expression profiling. Cell Tissue Res. 350, 317–331 (2012).
Li, C. et al. Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner. Int. J. Med. Sci. 9, 862–871 (2012).
Meng, M. et al. IL-1α regulates osteogenesis and osteoclastic activity of dental follicle cells through JNK and p38 MAPK pathways. Stem Cells Dev. 29, 1552–1566 (2020).
Ge, J. et al. Dental follicle cells participate in tooth eruption via the RUNX2-MiR-31-SATB2 loop. J. Dent. Res. 94, 936–944 (2015).
Wang, X. Z. et al. RUNX2 mutation impairs 1α,25-dihydroxyvitamin d3 mediated osteoclastogenesis in dental follicle cells. Sci. Rep. 6, 24225 (2016).
Ji, L. et al. RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway. Oral Dis. https://doi.org/10.1111/odi.14607 (2023).
Viale-Bouroncle, S., Gosau, M. & Morsczeck, C. NOTCH1 signaling regulates the BMP2/DLX-3 directed osteogenic differentiation of dental follicle cells. Biochem. Biophys. Res. Commun. 443, 500–504 (2014).
Viale-Bouroncle, S., Gosau, M. & Morsczeck, C. Laminin regulates the osteogenic differentiation of dental follicle cells via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway. Cell Tissue Res. 357, 345–354 (2014).
Nelson, P. et al. Transient receptor potential melastatin 4 channel controls calcium signals and dental follicle stem cell differentiation. Stem Cells 31, 167–177 (2013).
Zhaosong, M., Na, F., Shuling, G., Jiacheng, L. & Ran, W. Heterogeneity affects the differentiation potential of dental follicle stem cells through the TGF-β signaling pathway. Bioengineered 12, 12294–12307 (2021).
Gao, W., Chen, Y., Zhang, Y., Zhang, Q. & Zhang, L. Nanoparticle-based local antimicrobial drug delivery. Adv. Drug Deliv. Rev. 127, 46–57 (2018).
Siddiqui, Z. et al. Cells and material-based strategies for regenerative endodontics. Bioact. Mater. 14, 234–249 (2022).
Moussa, D. G. & Aparicio, C. Present and future of tissue engineering scaffolds for dentin-pulp complex regeneration. J. Tissue Eng. Regen. Med. 13, 58–75 (2019).
Yelick, P. C. & Sharpe, P. T. Tooth bioengineering and regenerative dentistry. J. Dent. Res. 98, 1173–1182 (2019).
Monteiro, N. & Yelick, P. C. Advances and perspectives in tooth tissue engineering. J. Tissue Eng. Regen. Med. 11, 2443–2461 (2017).
Smith, E. E. & Yelick, P. C. Bioengineering tooth bud constructs using gelma hydrogel. Methods Mol. Biol. 1922, 139–150 (2019).
Otsu, K. et al. Stem cell sources for tooth regeneration: current status and future prospects. Front. Physiol. 5, 36 (2014).
Mai, H. N., Kim, E. J. & Jung, H. S. Application of hiPSCs in tooth regeneration via cellular modulation. J. Oral. Biosci. 63, 225–231 (2021).
Kim, G. H. et al. Differentiation and establishment of dental epithelial-like stem cells derived from human ESCs and iPSCs. Int. J. Mol. Sci. https://doi.org/10.3390/ijms21124384 (2020).
Kobayashi, Y. et al. iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel. Bioact. Mater. 14, 290–301 (2022).
Kim, E. J. et al. Strategies for differentiation of hiPSCs into dental epithelial cell lineage. Cell Tissue Res. 386, 415–421 (2021).
Wu, M. et al. SHED aggregate exosomes shuttled miR-26a promote angiogenesis in pulp regeneration via TGF-β/SMAD2/3 signalling. Cell Prolif. 54, e13074 (2021).
Guo, H. et al. Odontogenesis-related developmental microenvironment facilitates deciduous dental pulp stem cell aggregates to revitalize an avulsed tooth. Biomaterials 279, 121223 (2021).
Chen, H. et al. Regeneration of pulpo-dentinal-like complex by a group of unique multipotent CD24a(+) stem cells. Sci. Adv. 6, eaay1514 (2020).
Na, S. et al. Regeneration of dental pulp/dentine complex with a three-dimensional and scaffold-free stem-cell sheet-derived pellet. J. Tissue Eng. Regen. Med 10, 261–270 (2016).
Xuan, K. et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aaf3227 (2018).
京公网安备11010802044758号