Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/β-Catenin in Dentin-Pulp Regeneration
Abstract
:1. Introduction
2. Materials and Methods
2.1. Source of Data
2.2. Search Method
- Related studies in Wnt/β-catenin signals
- Human (in vitro) and animal (in vivo) studies.
- Wnt/β-catenin in oral cavity-based publications.
- Bioactive materials on dental pulp cells via Wnt signals
- Unconvincing or poor evidence.
- Case report studies
- Incomplete text publications
- Incomplete data
2.3. PICO Framework
3. Results
4. Discussion
4.1. Wnt/β-Catenin Pathway in Odontogenesis
4.2. Wnt Ligands and Their Role in Dentin and Pulp Regeneration
4.2.1. Wnt1
4.2.2. Wnt3a
4.2.3. Wnt3a and Wnt10a in Dentin Bridge Formation
4.2.4. Wnt10a
4.2.5. Wnt10a, a Non-Cellular Agent for Dentin Pulp Regeneration
4.2.6. Wnt7b
4.2.7. Axin2
4.2.8. R-Spondin 2
4.3. Bioactive Molecules and Their Role in Dentin and Pulp Regeneration
4.3.1. Baicalin
4.3.2. Berberine
4.3.3. S-PRG Fillers as Dental Pulp Capping Agents
4.3.4. Vacuolar Protein 4B and Its Effect on the Wnt/β-Catenin Pathway
4.3.5. N-Cadherin
4.4. Lithium Chloride and Wnt/β-Catenin Pathway
4.5. Treated Dentin Matrix and Its Effect on hDPSCs via Wnt/β Catenin Pathway
4.6. Role of Wnt Signalling in Progression of Diabetic-Induced Cellular Aging
4.7. Role of Wnt Pathway in Dentin and Pulp Repair
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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S | Year | Author | Type of Study | Sample Size | Objective | Conclusion | Recommendation/Limitation |
---|---|---|---|---|---|---|---|
1 | 2012 | J Wang et al. [38] | In vitro | n = 8 3 molars 18–20 age | Role of Wnt/β-catenin signaling pathway in SCAP proliferation and differentiation. | Proliferation and odonto/osteogenic differentiation of SCAP are promoted by the Wnt/β-catenin signaling pathway. | Further study in SCAP mineralization and proliferation may bring improvement in dental tissue engineering. |
2 | 2013 | Ran Zhang et al. [39] | In vivo | Wnt signaling and its importance in cementogenesis and odontogenesis. | Wnt signaling encourages the differentiation of odontoblasts from mesenchyme. | Influence of Wnt signaling on tooth development. | |
3 | 2014 | Zichun Zhang et al. [33] | In vivo | 9 | Response of Wnt10a on DPSCs. | Proliferation of DPCS is promoted, and their odontoblastic differentiation is negatively regulated by Wnt10a. | Further research is vital to understand the biological effect of Wnt10a on DPCS. |
4 | 2014 | Nana Han et al. [40] | In vivo | β-catenin during the activation of Runx2 in DPCs augments odontoblastic differentiation. | Odontoblastic differentiation in tertiary dentin modulated by β-catenin. | The mechanism of reparative dentin formation remains unclear. | |
5 | 2015 | Danial J Hunter et al. [28] | In vivo | 72 mice | Response of injured pulp to amplified Wnt signaling resulting in superior pulp healing. | Amplified Wnt signaling caused pulp cells to differentiate into secretory odontoblasts, thus improving pulp vitality. | The role of amplified Wnt signaling on pulp cells plays a role in promoting pulp vitality, treating dental caries, and alternative approaches for root canal treatment. |
6 | 2015 | Athina Bakopoulou et al. [41] | In vitro | 3 molars age 18–24. DPSCs cultured from 3 donors. | The function of the Wnt/β-catenin pathway in the healing of pulpal injury resulted from resinous monomers via DPSC mediation. | DPSCs, under the effect of Wnt/β-catenin, participate in pulp healing after injury. | The analysis of stem cells is important for pulp regenerative therapy and bioactive molecule planning via tissue engineering through Wnt activation. |
7 | 2016 | Masato Tamura et al. [15] | Review Article | Determination of function of signaling molecules of Wnt in tooth. | Tooth development, maintenance, and turnover are regulated by both canonical and non-canonical Wnt pathway. | The Wnt signaling pathway and its progress in future therapeutics for tooth regeneration. | |
8 | 2017 | Hongyang LV et al. [42] | In vivo/In vitro | HDPCs cultured from 3 molars from 19 to 24 years of age. | Function of Wnt7b protein in HDPCs relocation and differentiation. | Wnt/β-catenin and JNK pathways partly have a role in the differentiation of HDPCs and are promoted by the Wnt7b protein. | Wnt7b can be used in the potential treatment of dental caries and tooth trauma. Wnt7b plays a role in maintaining the vitality of the tooth. |
9 | 2017 | Rebecca Babb et al. [13] | In vivo | The role of Axin 2 via Wnt/β-catenin signaling in tertiary dentinogenesis. | As a response to tooth injury, new odontoblast-like cells are formed via the Wnt signaling pathway, and Axin 2 cells provide a signal in reparative dentinogenesis. | Further study is required for stem cell-based tooth repair via the Wnt/β-catenin signaling pathway in secondary and tertiary dentinogenesis | |
10 | 2018 | Manahil Ali et al. [43] | In vivo/ In vitro | 21 | To check the enhancement of S-PRG cement through the addition of LiCl and its effect on hDPSCs. | S-PRG cement through the Wnt/β-catenin pathway enhances reparative dentin formation in rat teeth and promotes hDPSC profiles. | Inclination of reparative dentinogenesis in clinical trials needs to be further assessed. The interaction of Li ions with S-PRG fillers is not fully understood. |
11 | 2019 | Yuan Zhao et al. [44] | In vivo | 2 strains of Wnt reporter mice | The function of Wnt signaling in age-linked variations in pulp and its ability to respond to subacute traumas. | Amplification of Wnt signaling results in reparative/osteodentin organization, as the secretion of dentin from odontoblasts is regulated by this pathway. | Wnt signaling and its role in dentin secretion can be used to form biological pulp-capping material. |
12 | 2019 | Xi Lu et al. [19] | Review Article | Review of Wnt signaling pathway, its modulators, and their function in odontogenesis and therapeutic potential. | Tooth development is closely regulated by the canonical Wnt pathway. | The tooth regeneration method may be provided by a detailed study in Wnt signaling. | |
13 | 2019 | Anqian Wu et al. [45] | In vitro | (N) n = 20 pulp Ages 18–25 | Impact of berberine on DPSCs and their odontoblast differentiation. | By the stimulation of the Wnt pathway, berberine encourages odontoblast differentiation. | Berberine might be used as a new drug for the treatment of dental defects. |
14 | 2019 | Yuping Gong et al. [46] | In vivo | 20 | Role of Rspo2 in promoting hDPSCs to differentiate odontogenically through the Wnt/β-catenin pathway. | hDPSCs stimulated by Rspo2, both positive and negative, by enhancer and silencer agents, thus enhancing their proliferation and differentiation. | Future work of R-spondins and Wnt ligands could be on therapeutic use clinically. |
15 | 2019 | Xiaohui Lu et al. [47] | In vitro | n = 10 3 molars age 14–22 yrs | miR-140-5p impact on the odontoblastic differentiation of DPSC. | The odontoblastic differentiation of DPSCs is regulated by lowering miR-140-5p by targeting the Wnt/β-catenin pathway. | miR-140-5p can be used as a medicinal agent that could control odontoblastic differentiation in dental medicine. |
16 | 2019 | K. Yaemkleebua et al. [48] | In vivo | 32 rat molar pulps were used. | Hard tissue formation after application of pulp capping materials on pinpoint exposure and the role of Wnt signaling and cell cycle regulation. | Reparative dentinogenesis occurred with the application of pulp capping materials, and cyclin D1 expression was seen. | The association between Wnt signaling and reparative dentin formation might be used to comprehend the response of normal pulp in injured conditions. |
17 | 2019 | Yuhua Pan et al. [49] | In vivo In vitro | DPSCs culture from 3 molars of 18–20 yr Donors | The role of VPS4B in DPSCs via the Wnt/β-catenin signaling pathway. | DPSC differentiation and proliferation are regulated by VPS4B via the Wnt/β-catenin pathway. | Dentin dysplasia type1 could be treated via potential medicinal therapies by the formation of dentin and reparative endodontic therapy. |
18 | 2020 | LK Zaugg et al. [50] | In vivo/ In vitro | Adult male Wistar rats (7 wk old) and CD1 mice (6 wk old) | The Wnt/β-catenin signaling and its function in reparative dentinogenesis and how it is affected by the introduction of GSK3β inhibitor drugs. | GSK3β inhibitor results in the tertiary dentin formation at the defect region having the size of a human lesion; however, this is not true regeneration. | Augmentation of reparative dentinogenesis can be used potentially as a treatment in direct pulp capping. |
19 | 2021 | Nicha Tokavanich et al. [51] | Review Article | Wnt signaling and its effect on postnatal tooth development. | Wnt signaling may play a vital role as a target for root formation and tooth eruption disorders. | In-depth study of the Wnt signaling pathway may provide a path in the future for regenerative dentistry. | |
20 | 2021 | Miroku Hara et al. [52] | In vivo | 321 mice | Dentin bridge formation at pinpoint exposure and how the Wnt signaling and its molecules affect it. | The injured dental pulp is repaired by the stimulation of canonical Wnt signaling. | Wnt pathway activation by the dental pulp capping materials may be a new approach for vital pulp therapy. |
21 | 2021 | Zilong Deng et al. [53] | In vitro/In vivo | 3 molars Pulp 18–25 yr n = 5 mice | N-cadherin effect on DPSCs, in-vitro and in-vivo, and its function in odontogenic differentiation. | N-cadherin negatively regulates β-catenin activity in DPSCs. | Further study is required on how neurogenic differentiation of DPSCs is regulated by N-cadherin |
22 | 2021 | Jia Wang et al. [54] | In vivo | 2 transgenic mice | Role of Wnt signaling and distribution of BMP during postnatal root development. | Tooth root development is regulated by BMP and Wnt signaling pathway. | Further study is required for Wnt/β-catenin pathway regulation for matrix secretion and differentiation in postnatal tooth development. |
23 | 2021 | Anushree Vijaykumar et al. [55] | In vitro | Pulp culture from 1 and 2 molar 5–7 d mice | Dentin pulp complex and role of LiCl in its reparation and regeneration via Wnt/β-catenin pathway by inhibiting GSK3β. | LiCl results in reparative dentin formation, which has an improved structure. | GSK3β controls several transcription factors and various pathways; thus, the influence of LiCl on tertiary dentin formation may not be deemed exclusive to the Wnt/β-catenin pathway. |
24 | 2021 | Sirui Liu et al. [56] | In vitro In vivo | DPSCs culture donor’s teeth pulp 18–25 yr Wistar mice 26 | Wnt/β-catenin signaling role in hDPSCs and its odontogenic differentiation via TDM extract. | TDM via GSK3β activates the Wnt/β-catenin pathway in hDPSC and stimulates its odontogenic differentiation. | The mechanism for TDM-induced differentiation requires further study. |
25 | 2021 | Mona Asghari et al. [57] | In vitro | 4000 cells | Effect of hyperglycemia and function of Wnt pathway in senescence of pulp cells. | Hyperglycemia causes the aging of pulp cells. Cellular aging is induced via beta-catenin. | Further study is required to determine the role of beta-catenin and pulp regeneration in diabetic patients. |
26 | 2022 | Henry F Duncan et al. [58] | In vivo In vitro | MMP13 deficient mice and WT control mice were used for DPCs. | The effect and interaction of MMP13 with the Wnt signaling pathway. Its effect on tooth development, repair, and dentin pulp regeneration. | MMP13 controls the organization and regulation of tooth development in addition to dentin pulp regeneration. | This study found targets for new therapy for traumatized pulp by increasing repair response. |
27 | 2022 | Tingting Fu et al. [59] | In vitro | DPSCs Culture Donar teeth ≤16 yr | Role of SNHG1 in hDPSCs in odontogenic differentiation via Wnt/β-catenin signaling. | The Wnt/β-catenin pathway is silenced by IncRNA SNHG1 via miR-328-3p, resulting in the differentiation of hDPSCs. | Useful in regenerative endodontics. |
28 | 2023 | Waleerat Sukarawan et al. [60] | In vivo | 6 mice | To check in SHEDs the influence of Wnt3a on the odonto/osteogenic differentiation and reparative dentin production. | Wnt3a causes an increase in osteogenic differentiation, silencing of proliferation in SHEDs, advances tertiary dentin formation, and can be used as a biological molecule in vital pulp therapy. | An in-depth study is required to identify the function and role of Wnt3a in tissue engineering. |
29 | 2023 | Mengyuan Li et al. [61] | In vitro | DPSC In 6 well plates | Effect of Baicalin on DPSC differentiation via Wnt/β/NF-kB pathway. | Baicalin impedes both NF-Kb and Wnt/β-catenin pathways, thus promoting the differentiation of DPSCs, causing repair of pulp with early irreversible pulpitis. | Further investigation and research are required to apply it in the long-term |
30 | 2023 | Shintaro Sakatoku et al. [62] | In vitro | DPSC in 24 well plates | Role of Wnt10a and odontoblasts in regenerative dental pulp. | Odontoblasts expressing Wnt10a play an increased role in pulp regeneration, with dentin-inducing capacity. | A detailed study after transplantation is required to check the long-term effect of Wnt10a along with DKK1 levels in regenerated dental pulp. |
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Amir, M.; Jeevithan, L.; Barkat, M.; Fatima, S.H.; Khan, M.; Israr, S.; Naseer, F.; Fayyaz, S.; Elango, J.; Wu, W.; et al. Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/β-Catenin in Dentin-Pulp Regeneration. Cells 2024, 13, 1153. https://doi.org/10.3390/cells13131153
Amir M, Jeevithan L, Barkat M, Fatima SH, Khan M, Israr S, Naseer F, Fayyaz S, Elango J, Wu W, et al. Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/β-Catenin in Dentin-Pulp Regeneration. Cells. 2024; 13(13):1153. https://doi.org/10.3390/cells13131153
Chicago/Turabian StyleAmir, Mariam, Lakshmi Jeevithan, Maham Barkat, Syeda Habib Fatima, Malalai Khan, Sara Israr, Fatima Naseer, Sarmad Fayyaz, Jeevithan Elango, Wenhui Wu, and et al. 2024. "Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/β-Catenin in Dentin-Pulp Regeneration" Cells 13, no. 13: 1153. https://doi.org/10.3390/cells13131153