Silk proteins stimulate osteoblast differentiation by suppressing the Notch signaling pathway in mesenchymal stem cells
Abstract
Silk fibroins are biomaterials that have been applied to surgical sutures, drug delivery systems, food supplements, and tissue engineering. Studies have shown the antiadipogenic effects of silk proteins in 3T3-L1 cells and obese mice. Furthermore, other studies have shown that silk proteins increase osteogenic marker expression in osteoblast-like cells. Because osteogenic and adipogenic differentiation from common mesenchymal progenitor cells are often regulated reciprocally, we hypothesized that silk proteins would stimulate osteoblast differentiation. The objective of this study was to evaluate the effects of silk proteins on promoting osteoblast differentiation and identify the underlying mechanism. We showed that silk proteins dose dependently stimulated alkaline phosphatase (ALP) activity, osteoblast differentiation, and induced expression of osteoblast markers in C3H10T1/2 and M2-10B4 multipotent cells. In addition, silk proteins also induced the expression of osteoblast markers in primary rat bone marrow cells isolated from tibiae. Molecular studies showed that silk proteins suppressed the expression of Notch-activated genes and blocked activation of the Notch-specific reporter. Similarly, inhibiting Notch signaling with pharmacologic inhibitors and by small interfering RNA-mediated Notch1 silencing also induced ALP activity and messenger RNA expression. Finally, induction of ALP activity and messenger RNA expression by silk proteins was blunted in Notch1 knock-downed cells, further demonstrating Notch signaling as an important mediator for the pro-osteogenic effects of silk proteins. Taken together, our data suggest that silk proteins may serve as functional foods to promote bone healing and therapeutic interventions for bone fractures and osteoporosis.
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Silk fibroin can promote the upregulation of osteoblast differentiation markers such as ALP, Osterix, and Runx2 by inhibiting Notch signaling.
“Silk fibroin can promote the upregulation of osteoblast differentiation markers (such as ALP, Osterix, and Runx2) by inhibiting Notch signaling [36].”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [36]
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Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review
Zhu, S., Zhang, Q., Xu, X., Liu, Z., Cheng, G., Long, D., Cheng, L., & Dai, F. (2025) · Polymers · doi:10.3390/polym17060772 · Cited by 36 · see citing works
“Silk fibroin can promote the upregulation of osteoblast differentiation markers (such as ALP, Osterix, and Runx2) by inhibiting Notch signaling [36].”
- Authors
- Jung, S.-R., Song, N.-J., Yang, D. K., Cho, Y.-J., Kim, B.-J., Hong, J.-W., Yun, U. J., Jo, D.-G., Lee, Y. M., Choi, S. Y., & Park, K. W.
- Affiliations
- Sungkyunkwan University (KR)
- Gwangju Institute of Science and Technology (KR)
- Hallym University (KR)
- Konyang University (KR)
- Kyung Hee University (KR)
- Rural Development Administration (KR)
- ORCID
- Venue
- Nutrition Research
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 33
- Issue
- 2
- Pages
- 162-170
- ISSN
- 0271-5317 (ISSN-L)
- OpenAlex
- W2040334613
- Cited by
- 64
- References
- 37
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 9 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 4
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A101711)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- silk proteins, silk fibroin, osteogenic differentiation, Notch signaling, Notch1, alkaline phosphatase activity, mesenchymal stem cells, bone marrow cells, functional foods, bone regeneration, osteoporosis, bone fractures, adipogenesis
- MeSH terms
- Alkaline Phosphatase, Animals, Bone Marrow Cells, Cell Differentiation, Dose-Response Relationship, Drug, Fibroins, Osteoblasts, Osteogenesis, Osteoporosis, RNA, Messenger, Signal Transduction, Gene Expression, RNA, Small Interfering, Silk, Fractures, Bone, Mice, Rats, Receptor, Notch1, Mesenchymal Stem Cells
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