Insulin‐like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via m TOR pathway
Abstract
Insulin‐like growth factor 1 (IGF‐1) is a multifunctional peptide that can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSC s). However, it remains unclear whether IGF‐1 can promote osteogenic differentiation of human dental pulp stem cells (DPSC s). In our study, DPSC s were isolated from the impacted third molars, and treated with IGF‐1. Osteogenic differentiation abilities were investigated. We found that IGF‐1 activated the m TOR signaling pathway during osteogenic differentiation of DPSC s. IGF‐1 also increased the expression of runt‐related transcription factor 2 (RUNX 2), osteocalcin (OCN), osterix (OSX) and collagen type I (COL I) during this process. Rapamycin, an m TOR inhibitor, blocked osteogenic differentiation induced by IGF‐1. Meanwhile, CCK‐8 assay and flow cytometry results demonstrated that 10–200 ng/mL IGF‐1 could enhance proliferation ability of DPSC s and 100 ng/mL was the optimal concentration. In summary, IGF‐1 could promote proliferation and osteogenic differentiation of DPSC s via m TOR pathways, which might have clinical implications for osteoporosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IGF-1-dependent activation of mTOR induces human dental pulp stem cell differentiation toward an osteoblastic phenotype.
“Recent studies have confirmed that IGF-1-dependent activation of mTOR induces human dental pulp stem cell (DPSC) differentiation toward an osteoblastic phenotype.219”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [219]
Cites
1 retracted
Dan, H. C., Sun, M., Yang, L., Feldman, R. I., Sui, X.-M., Ou, C. C., Nellist, M. D., Yeung, R. S. W., Halley, D. J. J., Nicosia, S. V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205838200 · Cited by 370 · see citing works
RetractedPostnatal human dental pulp stem cells (DPSCs) in vitro and in vivo
Gronthos, S., Mankani, M. H., Brahim, J. S., Robey, P. G., & Shi, S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240309797 · Cited by 4,580 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608 · see citing works
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works
SHED: Stem cells from human exfoliated deciduous teeth
Miura, M., Gronthos, S., Zhao, M., Lu, B., Fisher, L. W., Robey, P. G., & Shi, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937635100 · Cited by 3,007 · see citing works
Huang, G. T. ‐., Gronthos, S., & Shi, S. (2009) · Journal of Dental Research · doi:10.1177/0022034509340867 · Cited by 1,876 · see citing works
Reaching a Genetic and Molecular Understanding of Skeletal Development
Karsenty, G., & Wagner, E. F. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00157-0 · Cited by 1,594 · see citing works
Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00568-3 · Cited by 1,555 · see citing works
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · see citing works
Yamaguchi, A., Komori, T., & Suda, T. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.4.0403 · Cited by 688 · see citing works
Toward delivery of multiple growth factors in tissue engineering
Chen, F., Zhang, M., & Wu, Z. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.04.053 · Cited by 655 · see citing works
Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells
Xian, L., Wu, X., Pang, L., Lou, M., Rosen, C. J., Qiu, T., Crane, J., Frassica, F., Zhang, L., Rodriguez, J. P., et al. (2012) · Nature Medicine · doi:10.1038/nm.2793 · Cited by 631 · see citing works
Pierdomenico, L., Bonsi, L., Calvitti, M., Rondelli, D., Arpinati, M., Chirumbolo, G., Becchetti, E., Marchionni, C., Alviano, F., Fossati, V., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000173794.72151.88 · Cited by 574 · see citing works
Takeda, S., Bonnamy, J.-P., Owen, M. J., Ducy, P. F., & Karsenty, G. (2001) · Genes & Development · doi:10.1101/gad.845101 · Cited by 518 · see citing works
[11] Measurement of growth and viability of cells in culture
Patterson, M. K. (1979) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(79)58132-4 · Cited by 514 · see citing works
Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?
Corradetti, M. N., & Guan, K.-L. (2006) · Oncogene · doi:10.1038/sj.onc.1209885 · Cited by 387 · see citing works
A review on endogenous regenerative technology in periodontal regenerative medicine
Chen, F., Zhang, J., Zhang, M., An, Y., Chen, F., & Wu, Z. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.019 · Cited by 378 · see citing works
Transcriptional Regulatory Cascades in Runx2-Dependent Bone Development
Liu, T. M., & Lee, E. H. (2012) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0527 · Cited by 377 · see citing works
Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities
Chen, F., & Jin, Y. J. (2009) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2009.0562 · Cited by 374 · see citing works
Isolation and Characterization of Postnatal Stem Cells from Human Dental Tissues
Jo, Y., Lee, H.-J., Kook, S. Y., Choung, H., Park, J., Chung, J.-H., Choung, Y., Kim, E., Yang, H., & Choung, P. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0192 · Cited by 365 · see citing works
Osteocalcin: Skeletal and extra‐skeletal effects
Neve, A., Corrado, A., & Cantatore, F. P. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24278 · Cited by 335 · see citing works
Celil, A. B., & Campbell, P. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503845200 · Cited by 324 · see citing works
Dental Pulp Stem Cells: A Promising Tool for Bone Regeneration
d’Aquino, R., Papaccio, G., Laino, G., & Graziano, A. (2008) · Stem Cell Reviews and Reports · doi:10.1007/s12015-008-9013-5 · Cited by 310 · see citing works
Laviola, L., Natalicchio, A., & Giorgino, F. (2007) · Current Pharmaceutical Design · doi:10.2174/138161207780249146 · Cited by 296 · see citing works
Periodontal tissue engineering by growth factors
Giannobile, W. V. (1996) · Bone · doi:10.1016/s8756-3282(96)00127-5 · Cited by 295 · see citing works
Runx2, Osx , and Dspp in Tooth Development
Chen, S., Gluhak‐Heinrich, J., Wang, Y., Wu, Y., Chuang, H.-H., Chen, L., Yuan, G., Dong, J., Gay, I. C., & MacDougall, M. J. (2009) · Journal of Dental Research · doi:10.1177/0022034509342873 · Cited by 266 · see citing works
An approachable human adult stem cell source for hard‐tissue engineering
Laino, G., Graziano, A., d’Aquino, R., Pirozzi, G., Lanza, V., Valiante, S., ROSA, A. D., Naro, F., Vivarelli, E., & Papaccio, G. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20526 · Cited by 238 · see citing works
BMP-2 Induces Osterix Expression through Up-regulation of Dlx5 and Its Phosphorylation by p38
Ulsamer, A., Ortuño, M. J., Ruiz-Gaspà, S., Susperregui, A. R. G., Osses, N., Rosa, J. L., & Ventura, F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704724200 · Cited by 214 · see citing works
Dental Pulp Stem Cells: A Promising Tool for Bone Regeneration
Graziano, A., d’Aquino, R., Laino, G., & Papaccio, G. (2008) · Stem Cell Reviews and Reports · doi:10.1007/s12015-008-9015-3 · Cited by 198 · see citing works
Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix
Baek, W., Lee, M., Jung, J., Kim, S., Akiyama, H., Crombrugghe, B. D., & Kim, J. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081248 · Cited by 192 · see citing works
Ma, L., Makino, Y., Yamaza, H., Akiyama, K., Hoshino, Y., Song, G., Kukita, T., Nonaka, K., Shi, S., & Yamaza, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051777 · Cited by 174 · see citing works
Qiao, M., Shapiro, P. S., Kumar, R., & Passaniti, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404480200 · Cited by 147 · see citing works
Yu, Y., Mu, J., Fan, Z., Lei, G., Yan, M., Wang, S., Tang, C., Wang, Z., Yu, J., & Zhang, G. (2012) · Histochemistry and Cell Biology · doi:10.1007/s00418-011-0908-x · Cited by 141 · see citing works
Chen, F., Zhao, Y., Wu, H., Deng, Z., Wang, Q., Zhou, W. J., Liu, Q., Dong, G., Li, K., Wu, Z., et al. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.05.014 · Cited by 129 · see citing works
Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification
Kaback, L. A., Soung, D. Y., Naik, A., Smith, N., Schwarz, E. M., O’Keefe, R. J., & Drissi, H. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21176 · Cited by 126 · see citing works
Romanelli, R. J., LeBeau, A. P., Fulmer, C. G., Lazzarino, D. A., Hochberg, A. M., & Wood, T. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704309200 · Cited by 120 · see citing works
Feng, X., Feng, G., Xing, J., et al. (2013) · Cell Biology International · doi:10.1002/cbin.10141 · Cited by 111 · see citing works
Self-citationBakopoulou, A., Leyhausen, G., Volk, J., Tsiftsoglou, A. S., Garefis, P., Koidis, P. T., & Geurtsen, W. (2010) · Calcified Tissue International · doi:10.1007/s00223-010-9438-0 · Cited by 110 · see citing works
Tu, Q., Valverde, P., Li, S., Zhang, J. C., Yang, P., & Chen, J. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0406 · Cited by 103 · see citing works
Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes
Paino, F., Ricci, G., ROSA, A. D., d’Aquino, R., Laino, L., Pirozzi, G., Tirino, V., & Papaccio, G. (2010) · European Cells and Materials · doi:10.22203/ecm.v020a24 · Cited by 96 · see citing works
Granero‐Moltó, F., Myers, T. J., Weis, J. A., Longobardi, L., Li, T., Yan, Y., Case, N. D., Rubin, J. E., & Spagnoli, A. (2011) · Stem Cells · doi:10.1002/stem.697 · Cited by 89 · see citing works
Postnatal growth and bone mass in mice with IGF-I haploinsufficiency
He, J., Rosen, C. J., Adams, D. J., & Kream, B. E. (2006) · Bone · doi:10.1016/j.bone.2005.11.021 · Cited by 79 · see citing works
Kanbur, N., Derman, O., & Kinik, E. (2004) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-004-0544-9 · Cited by 70 · see citing works
Blom, S., Holmstrup, P., & Dabelsteen, E. (1992) · Journal of Periodontology · doi:10.1902/jop.1992.63.12.960 · Cited by 64 · see citing works
Supeno, N. E., Pati, S., Hadi, R. A., Ghani, A. R. I., Mustafa, M. Z., Abdullah, J. M., Idris, F. M., Han, X., & Jaafar, H. (2013) · International Journal of Medical Sciences · doi:10.7150/ijms.5325 · Cited by 57 · see citing works
Pulp tissue from primary teeth: new source of stem cells
Telles, P. D. S., Machado, M. A. D. A. M., Sakai, V. T., et al. (2011) · Journal of Applied Oral Science · doi:10.1590/s1678-77572011000300002 · Cited by 56 · see citing works
Type II/III Runx2/Cbfa1 is required for tooth germ development
Kobayashi, I., Kiyoshima, T., Wada, H., et al. (2005) · Bone · doi:10.1016/j.bone.2005.10.026 · Cited by 48 · see citing works
Carvallo, L., Henríquez, B., Paredes, R., Olate, J., Oñate, S. A., van Wijnen, A. J., Lian, J. B., Stein, G. S., Stein, J. L., & Montecino, M. A. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21267 · Cited by 42 · see citing works
Formation of bone-like tissue by dental follicle cells co-cultured with dental papilla cells
Bai, Y., Bai, Y., Matsuzaka, K., et al. (2010) · Cell and Tissue Research · doi:10.1007/s00441-010-1046-9 · Cited by 36 · see citing works
Effects of insulin‐like growth factor I on alveolar bone remodeling in diabetic rats
Fang, Y., Wang, L. ‐., Du, F., et al. (2012) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2012.01512.x · Cited by 32 · see citing works
[Mechanism of transcriptional regulation by Runx2 in osteoblasts].
Komori, T. (2006) · PubMed · Cited by 25 · see citing works
Hanai, Y., Tokuda, H., Ishisaki, A., et al. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.02.014 · Cited by 24 · see citing works
Youssef, A., Iosef, C., & Han, V. K. M. (2014) · Endocrinology · doi:10.1210/en.2013-1842 · Cited by 20 · see citing works
Tiago, D. M., Cancela, M. L., & Laizé, V. (2010) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-010-0243-7 · Cited by 19 · see citing works
IGF-I improved bone mineral density and body composition of weaver mutant mice
Yao, W., Zhong, J., Yu, J., Warner, T., Božić, T., Ye, P., D’Ercole, A. J., Hock, J. M., & Lee, W. (2008) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2008.04.006 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Feng, X., Huang, D., Lu, X., Feng, G., Xing, J., Lu, J., Xu, K., Xia, W., Meng, Y., Tao, T., Li, L., & Gu, Z.
- Affiliations
- Affiliated Hospital of Nantong University (CN)
- Department of Stomatology Affiliated Hospital of Nantong University Nantong China
- Nantong University (CN)
- Corresponding author
- Gu, Zhifeng
- Venue
- Development, Growth & Differentiation
- Publisher
- Wiley
- Published
- 2014-11-11
- Volume
- 56
- Issue
- 9
- Pages
- 615-624
- ISSN
- 0012-1592 (ISSN-L)
- 1440-169X
- OpenAlex
- W2056522693
- Cited by
- 101
- References
- 56
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 14 · 2015: 6
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development Growth & Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese National Natural Science Foundation (81401603)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- insulin-like growth factor I, dental pulp stem cells, osteogenic differentiation, mTOR signaling, cell proliferation, Runx2, osteocalcin, Osterix, type I collagen, rapamycin, osteoporosis, third molar
- MeSH terms
- Adolescent, Adult, Cell Differentiation, Dental Pulp, Female, Humans, Insulin-Like Growth Factor I, Male, Osteogenesis, Stem Cells, Signal Transduction, Cell Proliferation, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review