Skip to main content
Download PDF

TGF-β promotes the proliferation and osteogenic differentiation of dental pulp stem cells a systematic review and meta-analysis

European Journal of Medical Research volume 28, Article number: 261 (2023) Cite this article

Abstract

Background

Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-β has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-β on the osteogenesis and proliferation of dental pulp stem cells.

Methods

We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment.

Results

The pooled data showed that TGF-β could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-β increases the A490 index (SMD 3.11, 95% CI [0.54–5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81–6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25–8.16]) and Runx-2 (SMD 3.37, 95% CI [− 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20–7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [− 1.76 to 9.51]) in dental pulp stem cells.

Conclusions

TGF-β promotes the proliferation and osteogenesis of dental pulp stem cells.

Introduction

The transforming growth factor-β (TGF-&beta/TGF-β) subfamily mainly includes three isoforms of TGF-β1–3, which have similar biological activity and high homology in amino acid sequence [1], and TGF-β is a cytokine that is secreted by various cell types, including macrophages, and functions in cell growth, cell differentiation, apoptosis and cellular homeostasis by binding to its receptor, the TGFβ type II receptor. TGF-β mRNA and its protein were expressed in different stages of tooth germ formation, including early bud stage and root dentin formation. TGF superfamily growth factor mediates transduction signals through its corresponding receptors [2]. For example, the TGF-β, the classical signal transduction pathway, is mediated by Sma and Mad proteins (Smad protein) and transduced by TGF-β1 receptor (TGF-βR1) and TGF-βR2 [3]. Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Proliferation and differentiation of DPSCs and up-regulation of various growth factors were observed during tooth development and pulp repair [4]. Bone sialoprotein (BSP) is an acidic glycoprotein in the extracellular matrix, and its tissue distribution is relatively limited [5]. It is mainly distributed in mineralized tissues (such as bone and teeth) and calcified cartilage and bone junction. Its content accounts for a lot of the non-glial protein in the bone extracellular matrix. The BSP is the indicator for the proliferation of dental pulp. Osteoblasts and odontoblasts mainly synthesize osteocalcin, and proliferative chondrocytes synthesize some. It plays an essential role in regulating bone calcium metabolism. It is a new biochemical marker for studying bone metabolism [6], which is used in studies as an indicator to assess the mineralization of dental pulp. Runt-related transcription factor 2 is an essential protein for osteoblast differentiation, which we use to evaluate the proliferation of dental pulp stem cells.

Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts [7]. This transform may have potential clinical value in dental fields, such as tooth transplantation or tooth regeneration. More and more researchers have supported the critical role of TGF-β in promoting cell growth and differentiation, including its effect on the proliferation and differentiation of dental pulp stem cells [8,9,10]. Many animal experiments or trials on the differentiation of human dental pulp stem cells and TGF-β have been carried out, and conclusions are quite different [11,12,13,14,15,16,17,18,19,20,21,22,23]. The purpose of this study was to summarize the results of the studies above and determine whether TGF-β promotes the proliferation and osteogenic differentiation of dental pulp stem cells.

Methods

Literature search

We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and CNKI (from August 12, 2012 to September 31, 2021) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1(Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. We included both animal experiments and trials on samples from human teeth. These studies were excluded under the following circumstances: This study is not a clinical randomized controlled trial. 2. Research objects or results and interventions do not meet the inclusion criteria. 3. Sample from people or animals with teeth diseases, which may cause uncertainty of outcomes. 4. The incomplete data or full text cannot be obtained. 5. Any conference papers, reviews, case reports, and lessons learned, repetitive literature (multilingual papers retain only the earliest literature) will also be rejected. Moreover, we excluded those indicators and outcomes with insufficient sample size or literature number. We provided a flow chart for the progression of literature search and inclusion or exclusion of studies in Fig. 1. The review was reported according with PRISMA guidelines (Additional file 1: PRISMA Checklist).

Fig. 1
figure 1

Flow chart of study identifying

Full size image

Data analysis

We summarized the effect of TGF-β on proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1(Col-1), osteocalcin (OCN), Runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Furthermore, we drew a forest plot by Stata16.1 software for each outcome. We conducted a sensitivity analysis, data statistics, heterogeneity, and publication bias test by STATA version 16.1 (STATA 2020). After discussion, we set the critical value of I-square as 45%. When the heterogeneity is more significant than this value, we believe that the consistency of the sample is poor. We performed Begg's test and egger's test to check the publication bias. Quality assessments of each study included were performed by Cochrane's tool for quality assessments of random-controlled trials [24].

Quality assessment and data extractions

We used Revman 5.4.1 (Revman 2020) software to evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment: 1. Random sequence generation 2. Allocation concealment 3. Blinding of participants and personnel 4. Blinding of outcome assessment 5. Incomplete outcome data 6. Selective reporting 7. Other bias. Results are provided in Fig. 2. Three reviewers (Pengfei Gao, Qi Li, Hui Dong) independently recorded the TGF type, animal species and strains, animal age, and body weight, dose frequency, type of the control group, outcome measures, course of treatment, interventions, adverse reactions, and other characteristics of the included studies, which we summarized in Table 1: Research characteristics.

Fig. 2
figure 2

Risk bias

Full size image
Table 1 Characteristics of studies
Full size table

Result

Literature search

We have identified a total of 479 studies interested TGF-β and proliferation and differentiation of dental pulp stem cells, from which we finally included a total of 13 studies with animal or human dental pulp cells samples from August 12, 2012 to September 31, 2021, on published papers or websites. These studies were excluded under the following circumstances: This study is not a randomized controlled trial. 2. Research objects or results and interventions do not meet the inclusion criteria. 3. Sample from people or animals with teeth diseases, which may cause uncertainty of measures. 4. The complete data or full text cannot be obtained. 5. Any conference papers, reviews, case reports, and lessons learned, repetitive literature (multilingual papers retain only the earliest literature) will also be rejected. In addition, we excluded those indicators and outcomes with insufficient sample size or literature number. We finalized the following six indicators as the outcomes of this systematic review and meta-analysis: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), Runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules.

Characteristics of studies

Three reviewers (Pengfei Gao, Qi Li, Hui Dong) independently recorded the TGF type, animal species and strains, animal age, and body weight, dose frequency, control group type, outcomes, course of treatment, interventions, adverse reactions, and other characteristics of the included studies, which we summarized in Table 1: Research characteristics. The results showed that most samples were from children aged 2–4 years or animals weighing 1–3 kg, mainly rabbits. What is more, the observation period is 7 days in most studies. The main types of TGF are β3 and β1. For more details, see Table 1: Research characteristics.

Data analysis

The TGF types were mainly TGF-β-1, TGF-β-3, except for TGF-β2. The included studies were all randomized controlled trials of samples from animals or people. Furthermore, publication bias has not existed in any outcome included. The heterogeneity of most results is high, suggesting that the evidence we provide is of medium quality and credibility.

A 490 Index

A total of 9 studies with DPSCs samples reported differences in the A490 index between the control group and the TGF-β group. All studies were randomized controlled trials of samples from animals or people. The TGF types included were mainly TGF-β-1 and TGF-β-3. We synthesized the data using Stata 16.1 software. A heterogeneity test was also performed using Stata16.1 software, and it was found that I-square was 82.7%, P < 0.001. Therefore, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 3.11, 95% CI [0.54–5.69]), suggesting that TGF-β promoted the proliferation of dental pulp stem cells. We provide a forest graph in Fig. 3.

Fig. 3
figure 3

A490

Full size image
BSP

A total of 7 studies with DPSCs samples reported differences in the content of BSP between the control group and the TGF-β group. All studies were randomized controlled trials of samples from animals or people. The TGF types included were mainly TGF-β-1 and TGF-β-3. Data were summarized using Stata 16.1 software. A heterogeneity test was also performed using Stata16.1 software, and the I-square was equal to 76.3%, P < 0.001, which suggests a higher heterogeneity than we set before. Hence, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 3.11, 95% CI [0.81–6.77]), suggesting that TGF-β promotes the osteogenesis and proliferation of the dental pulp stem cells. We provide a forest graph in Fig. 4 for BSP. We performed Begg's test and egger's test to evaluate the potential publication bias and found no significant publication bias in the studies included in BSP. For more details, see Fig. 5.

Fig. 4
figure 4

Content of BSP

Full size image
Fig. 5
figure 5

Content of BSP

Full size image

Col-1

A total of 4 studies with DPSCs samples reported differences in the expression of Col-1 in dental pulp stem cells between the control group and the TGF-β group. All studies were randomized controlled trials of samples from animals or people. The TGF types included were mainly TGF-β-1 and TGF-β-3. Data were summarized using Stata 16.1 software. Heterogeneity test was also performed using Stata16.1 software, and the I-square was equal to 68.7%, P < 0.001, which is higher heterogeneity than we set before. The evidence is medium-quality evidence. Moreover, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 4.71, 95% CI [1.25–8.16]), suggesting that TGF-β promotes the proliferation of dental pulp stem cells. We provide a forest graph in Fig. 6 for the expression of Col-1. We performed Begg's test and egger's test to evaluate the potential publication bias and found no significant publication bias in the studies included in the subgroup of expression of Col-1. For more details, see Fig. 7.

Fig. 6
figure 6

Expression of Col-1

Full size image
Fig. 7
figure 7

Expression of Col-1

Full size image
OCN

Five studies with DPSCs samples reported differences in OCN content between the control group and the TGF-β group. The TGF types were mainly TGF-β-1, TGF-β-3, except for TGF-β2. We synthesized the content of OCN using Stata 16.1 software and found the included studies were all randomized controlled trials of samples from animals or people. A heterogeneity test was also performed by Stata16.1 software, and it was found that I-square was 76.6%, P = 0.002. Therefore, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 4.32, 95% CI [1.20–7.44]), suggesting that TGF-β promoted the mineralization and calcification of dental pulp stem cells. We provide a forest graph in Fig. 8. Stata16.1 performed Begg's test and egger's test, and the publication bias was not significant. For more details, see Fig. 9.

Fig. 8
figure 8

Content of OCN

Full size image
Fig. 9
figure 9

Content of OCN

Full size image

Runx-2

A total of five studies with DPSCs samples reported differences in the expression of Runx-2 in dental pulp stem cells between the control group and the TGF-β group. All studies were randomized controlled trials of samples from animals or people. The TGF types included were TGF-β-1 and TGF-β-3. The expression size was summarized using Stata 16.1 software. The heterogeneity test was also performed using Stata16.1 software, and the I-square was equal to 85.4%, P < 0.001, which is higher heterogeneity than we set before. In addition, the evidence is medium-quality evidence. In addition, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 3.37, 95% CI [− 0.63 to 7.36]), suggesting that TGF-β promotes the proliferation of dental pulp stem cells. We provide a forest graph in Fig. 10 for the expression of Runx-2. We performed Begg's test and egger's test to evaluate the potential publication bias and found no significant publication bias in the studies included in the subgroup of expression of Runx-2. For more details, see Fig. 11.

Fig. 10
figure 10

Expression of Runx-2

Full size image
Fig. 11
figure 11

Expression of Runx-2

Full size image

The mineralized nodules

Two studies identified with DPSCs samples reported differences in the number of mineralized nodules between control and TGF-β groups. The TGF types were mainly TGF-β-1, TGF-β-3, except for TGF-β2. We synthesized the number of mineralized nodules in all the samples included by Stata 16.1 software and found the included studies were all randomized controlled trials of samples from animals or people. We performed a heterogeneity test by Stata16.1 software, in which we found that the I-square was 75.6%, P = 0.043. Therefore, we used SMD in a random effect model as an indicator to evaluate the overall effect and found (SMD 3.87, 95% CI [− 1.76 to 9.51]), suggesting that TGF-β does not increase the number of mineralized nodules in the dental pulp. We provide a forest graph in Fig. 12. Stata16.1 performed Begg's test and egger's test, and the publication bias was not significant. For more details, see Fig. 13.

Fig. 12
figure 12

Number of mineralized nodules

Full size image
Fig. 13
figure 13

Number of mineralized nodules

Full size image

Discussion

Findings

The pooled data showed that TGF-β could promote the proliferation and osteogenesis of dental pulp stem cells. All the outcomes summarized supported this conclusion except for the number of mineralized nodules: TGF-β increased the A490 index, promoted the production of BSP, promoted the expression of Col-1 and Runx-2, increased the content of OCN in dental pulp, and had no significant effect on the number of mineralized nodules in dental pulp stem cells. Samples included in this study were from mammalian and human dental pulps. Mammalian multipotent stem cells and multipotent stem cells have suitable homology and similarity. Hence, we combined the indicators of these samples to obtain a conclusion applicable to mammals and humans. The TGF-β family consists of 33 members, such as TGF-βs, activators, inhibin, and bone morphogenetic protein (BMP). TGF-βs [25] are mainly divided into TGF-β1, TGF-β2, and TGF-β3. Among them, TGF-β1 in TGF-βs has molecular functions, such as regulating cell proliferation, differentiation and wound healing, which has been reported to play an essential role in the pathophysiological processes, such as liver fibrosis [25,26,27,28]. However, it needs to be noted that there is a review about the part of TGF-β on articular cartilage. In cartilage formation, TGF-β triggers the aggregation of MSC. After aggregation, TGF-β signaling further stimulates chondrocyte proliferation and inhibits chondrocyte hypertrophy and maturation, which may challenge our conclusion [29]. Human dental pulp stem cells (HDPSCs) are adult stem cells derived from ectoderm and derived migrating neural crest cells. DPSCs can differentiate into odontoblasts, osteoblasts, adipocytes, chondrocytes, muscle cells, and neuronal cells under suitable culture conditions in vitro and in vivo. The ability of dental differentiation is very essential in oral research [30]. It has been reported that osteogenic induction can significantly enhance the mineralization ability of DPSCs, and TGF-β is a potent inducer of osteogenesis [31,32,33]. However, previous studies have drawn different conclusions on the osteogenic induction of DPSCs by TGF-β, especially on the role of TGF-β in promoting dental pulp mineralization. This review aims to determine the effects of TGF-β on the osteogenesis and proliferation of the dental pulp stem cells and to add new evidence for the physiological effects of TGF-β on mammals and humans.

Heterogeneity

We believe that heterogeneity is considerable when I-squared is greater than 45%, which is generally lower than the heterogeneity of measures in this study. Furthermore, the possible sources of the heterogeneities were thought to be the following items: 1. We synthesized samples from human and mammalian dental pulps. Although this does not bring problems in ethical and physiological perspectives, it may lead to heterogeneity; 2. Different researchers and laboratories may have significant differences in the observation of sample indicators; 3. The animal weight included in this review was somehow different, which means that data may come from mammals of different ages. The degree of osteogenesis varies with age, leading to the heterogeneity of osteogenesis and mineralization indicators. Moreover, the human samples included in this review come from people of different ages, mainly children and infants.

Shortcomings

There are shortcomings in this review: 1. The number of studies and samples included about some outcomes is relatively small, leading to the contingency of results. 2. The TGF-β types included in this review were only included TGF-β1 and TGF-β3, while the effect of TGF-β2 on dental pulp stem cells was not discussed. 3. This review only summarized the effects of TGF-β on the osteogenesis and proliferation of dental pulp stem cells from the perspectives of morphology and molecular biology. Relevant physiological and embryological mechanisms cannot be demonstrated by the outcomes of this review, which may require more studies to provide more evidence.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Abbreviations

DPSCs:

Dental pulp stem cells

CNKI:

China national knowledge infrastructure

BSP:

Bone sialoprotein

Col-1:

Col plasmid-1

OCN:

Osteocalcin

Runx-2:

Runt-related transcription factor 2

TGF-&beta/TGF-β:

Transforming growth factor-&beta;

Smad protein:

Sma and Mad proteins

TGF-βR1:

TGF-β1 receptor

BMP:

Bone morphogenetic protein

HDPSCs:

Human dental pulp stem cells

References

  1. Marit NH, Richard TH, Lynn MM. TGF-beta and related proteins in development, an MCDB/ISU symposium. Ames, Iowa, September 20–23, 1991. Mol Reprod Dev. 1992;32(2):89–184.

    Google Scholar 

  2. Huang XF, Chai Y. TGF-ß signalling and tooth development. Chin J Dent Res. 2010;13(1):7–15.

    CAS  PubMed  Google Scholar 

  3. Chen W, Huang X, Peng A, et al. Kangquan recipe regulates the expression of BAMBI protein via the TGF-β/Smad signaling pathway to inhibit benign prostatic hyperplasia in rats. Evid Complement Alternat Med. 2019;2019:6281819.

    Google Scholar 

  4. Nuti N, Corallo C, Chan BM, et al. Multipotent differentiation of human dental pulp stem cells: a literature review. Stem Cell Rev Rep. 2016;12(5):511–23.

    Article  CAS  PubMed  Google Scholar 

  5. Ganss B, Kim RH, Sodek J. Bone sialoprotein. Crit Rev Oral Biol Med. 1999;10(1):79–98.

    Article  CAS  PubMed  Google Scholar 

  6. Mizokami A, Kawakubo-Yasukochi T, Hirata M. Osteocalcin and its endocrine functions. Biochem Pharmacol. 2017;132:1–8.

    Article  CAS  PubMed  Google Scholar 

  7. Hu X, Zhong Y, Kong Y, et al. Lineage-specific exosomes promote the odontogenic differentiation of human dental pulp stem cells (DPSCs) through TGFβ1/smads signaling pathway via transfer of microRNAs. Stem Cell Res Ther. 2019;10(1):170.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chen YJ, Yao CC, Huang CH, et al. Hexosamine-induced TGF-β signaling and osteogenic differentiation of dental pulp stem cells are dependent on N-acetylglucosaminyltransferase V. Biomed Res Int. 2015;2015:924397.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Qi X, Xiao Q, Sheng R, Jiang S, et al. Endogenous GDF11 regulates odontogenic differentiation of dental pulp stem cells. J Cell Mol Med. 2020;24(19):11457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gopinath VK, Soumya S, Mohammad MG. Ror β expression in activated macrophages and dental pulp stem cells. Int Endod J. 2021;54(3):388–98.

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, He T, Liu J, et al. Synergistic effects of overexpression of BMP-2 and TGF-β3 on osteogenic differentiation of bone marrow mesenchymal stem cells. Mol Med Rep. 2016;14(6):5514–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wu Z. Effects of TGF-β_3 and dental pulp stem cells combined with Bio-OSS bone meal on bone defect repair in animals. In: Hoga M, editor. (01), 2015.

  13. Halik MI. Study on the osteogenic differentiation ability of rabbit dental pulp stem cells induced by heparin promoting transforming growth factor-β_3 in vitro. In: Hoga M, editor. (10), 2016.

  14. Khalik MI, Aini J, Xiaotao C, et al. In vitro study of the osteogenic differentiation potential of TGF-β3 on rabbit dental pulp stem cells under constant magnetic field. J Clin Stomatol. 2019;35(12):719–23.

    Google Scholar 

  15. Ababekli G. Effects of local combined application of TGF-β3 and DPSCs on immediate osseointegration of rabbit implants. In: Hoga M, editor. (11), 2018.

  16. Weiqian G, Yuming Z, Ge L. Human recombinant transforming growth factor β_1 promotes the proliferation and mineralization of dental pulp stem cells. J Peking Univ (Med Sci). 2017;49(04):680–4.

    Google Scholar 

  17. Alone, Hoga M, Keiko W. Effect of exogenous transforming growth factor-β_3 combined with rabbit pulp stem cells on expression of transforming growth factor-β_3 in rabbit bone defect osteoblasts. Chin J Pract Diagn Ther. 2017;31(06): 525–9.

  18. Ai X, Guitang W, Xingrong L. Effects of insulin-like growth factor-i and transforming growth factor-β1 on proliferation and differentiation of human dental pulp stem cells. Mod Prev Med. 2014;41(12):2237–40.

    Google Scholar 

  19. Liming J, Ge S, Business Itso, Chen X. Effect of transforming growth factor β1 on osteogenic differentiation of human dental pulp stem cells. Chin J Pract Stomatol. 2018;11(09): 530–3.

  20. Ernival E, Zhang X, Maimamtimin K, et al. In vitro study of transforming growth factor β3 promoting osteogenic differentiation of rabbit dental pulp stem cells. J Pract Stomatol. 2019;35(04):485–9.

    Google Scholar 

  21. Fei R, Jinmei L, et al. Effects of transforming growth factor β3 on proliferation and mineralization of human deciduous pulp stem cells. Chin Tissue Eng Res. 2014;18(28):4542–8.

    Google Scholar 

  22. Liu X, Hoga M, Khalik MI, et al. Effects of transforming growth factor-β_3 on proliferation and osteogenic differentiation of rabbit dental pulp stem cells. Chin J Pract Diagn Ther. 2016;30(03):242–5.

    Google Scholar 

  23. Fei R, Hui SD, et al. effect of transforming growth factor β3 combined with heparin on differentiation of human deciduous dental pulp stem cells into odontoblast-like cells. J Pract Med. 2014;30(12):1887–90.

    Google Scholar 

  24. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tzavlaki K, Moustakas A. TGF-β signaling. Biomolecules. 2020;10(3):487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lodyga M, Hinz B. TGF-β1—a truly transforming growth factor in fibrosis and immunity. Semin Cell Dev Biol. 2020;101:123–39.

    Article  CAS  PubMed  Google Scholar 

  27. Kim KK, Sheppard D, Chapman HA. TGF-β1 signaling and tissue fibrosis. Cold Spring Harb Perspect Biol. 2018;10(4):a022293.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mu M, Zuo S, Wu RM, et al. Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway. Drug Des Dev Ther. 2018;12:4107–15.

    Article  CAS  Google Scholar 

  29. Lizhi Z, Zhen W, Zhang S. The role of transforming growth factor β signaling in osteoarthritis. Chin J Bone Joint Surg. 2019;12(09):727–32.

    Google Scholar 

  30. Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res. 2009;88(9):792–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wu M, Chen G, Li YP. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Crane JL, Cao X. Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling. J Clin Invest. 2014;124(2):466–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen G, Deng C, Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012;8(2):272–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Stomatology, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, 233030, China

    Pengfei Gao, Chanjuan Liu, Hui Dong, Qi Li & Yunfang Chen

  2. Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China

    Pengfei Gao, Chanjuan Liu, Hui Dong, Qi Li & Yunfang Chen

Authors
  1. Pengfei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chanjuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yunfang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PG: investigation, resources, CL: formal analysis, writing—original draft, HD: validation, writing—review and editing, QL: data curation, visualization, YC: conceptualization, methodology, supervision, project administration.

Corresponding author

Correspondence to Yunfang Chen.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:

PRISMA Checklist.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, P., Liu, C., Dong, H. et al. TGF-β promotes the proliferation and osteogenic differentiation of dental pulp stem cells a systematic review and meta-analysis. Eur J Med Res 28, 261 (2023). https://doi.org/10.1186/s40001-023-01227-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-023-01227-y

Keywords

European Journal of Medical Research

ISSN: 2047-783X

Contact us