20-Hydroxyecdysone-induced bone morphogenetic protein-2-dependent osteogenic differentiation through the ERK pathway in human periodontal ligament stem cells
Abstract
20-Hydroxyecdysone, an ecdysteroid hormone, can induce osteogenic differentiation in mesenchymal stem cells. Periodontal ligament stem cells (PDLS cells) have mesenchymal-stem-cell-like qualities and are considered as one of the candidates of future clinical application in periodontitis treatment. However, there are no studies describing the effect of 20-Hydroxyecdysone on PDLS cells. In this paper, we report a detailed study on the effect of 20-Hydroxyecdysone on PDLS cell proliferation in vitro. PDLS cells were developed from human PDL cells and were treated with 20-Hydroxyecdysone to understand different aspects of its effects. 20-Hydroxyecdysone promoted PDLS cell proliferation; significantly increased the gene expression levels of runt-related transcription factor 2, alkaline phosphatase (ALP), type I collagen, and osteocalcin. Moreover, 20-Hydroxyecdysone enhanced bone formation by PDLS cells and significantly increased bone morphogenetic protein-2 (BMP-2) mRNA and protein expression. However, 20-Hydroxyecdysonemediated increase in ALP activity was blocked with a BMP-2-specific neutralizing antibody or with the antagonist noggin; and20-Hydroxyecdysone mediated induction of BMP-2 expression and increase of ALP activity were abolished by the extracellular regulated protein kinase (ERK) MAPK pathway inhibitor PD98059. 20-Hydroxyecdysone also increased the phosphorylation of ERK. These findings provide evidence to state that 20-Hydroxyecdysone stimulates cell proliferation and induces osteogenic differentiation through the induction of BMP-2 expression in PDLS cells. It also shows that the ERK pathway is involved in 20-Hydroxyecdysone induced BMP-2 expression and osteogenic differentiation. These results are suggesting its potential as a drug for periodontal regenerative therapy.
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Ecdysterone increased proliferation and bone differentiation in periodontal ligament cells.
“Ecdysterone increased proliferation and bone differentiation in these cells [31].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [31]
BMP-2 and ALP were increased in an Erk/MAPK pathway-dependent manner in periodontal ligament cells.
“The bone morphogenic protein 2 (BMP-2) and ALP were increased in an extracellular-dependent kinase (Erk)/MAPK pathway-dependent manner.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [31]
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- Authors
- Jian, C.-X., Liu, X.-F., Hu, J., Li, C.-J., Zhang, G., Li, Y., Zhu, J.-W., & Tan, Y.-H.
- Affiliations
- Army Medical University (CN)
- General Hospital of Jinan Military Command (CN)
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 698
- Issue
- 1-3
- Pages
- 48-56
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2010248220
- Cited by
- 18
- References
- 48
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81170934, 30973334)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- 20-hydroxyecdysone, ecdysteroids, periodontal ligament stem cells, osteogenic differentiation, BMP-2, MAPK/ERK pathway, cell proliferation, alkaline phosphatase, periodontal regeneration, periodontitis, noggin, PD98059
- MeSH terms
- Alkaline Phosphatase, Cell Differentiation, Ecdysterone, Gene Expression Regulation, Humans, Osteogenesis, Periodontal Ligament, Stem Cells, Signal Transduction, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Bone Morphogenetic Protein 2
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