β-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway
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Graphical Abstract: Schematic illustrations of the fabrication of the bone defect model and action of β-Ecd in promoting bone regeneration and repair of bone defects. We established a rat model of a femoral bone defect in vivo to evaluate the effect of β-Ecd on bone regeneration. Rats injected intraperitoneally with 72 mg/kg β-Ecd showed a higher degree of ossification of regenerated bone tissue at the site of the bone defect at weeks 4 and 8. β-ecdysterone binding to the BMP2 receptor activates SMAD1 to bind to SMAD1/5/8, promotes RUNX2 and OSTERIX replication in the nucleus, and mediates bone regeneration. This study provides a new approach to the treatment of bone injury and degenerative diseases represented by bone defects and osteoporosis.
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Ecdysterone does not appear to possess any severe side effects.
“Furthermore, ecdysterone does not appear to possess any severe side effects [19,47,49,50,51,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [74]
The Results section reports no signs of liver or kidney toxicity or weight loss in treated rats, and the Conclusion describes β-ecdysterone as having good biosafety in the mammalian models studied. That supports the cautious safety claim, but not an unrestricted claim about side effects: the Discussion also reports a toxic effect on cells at higher concentrations. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThis osteogenic effect happened via the BMP-2/Smad/Runx2/Osterix pathway.
“However, this happened via the BMP-2/Smad/Runx2/Osterix pathway, which revealed a new connection as BMP-2 had been related earlier to the Erk/MAP kinase pathway [43].”
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 [42]
Ecdysterone stimulated osteogenic osteoblast proliferation and differentiation in vitro and bone regeneration in vivo.
“Others reported that ecdysterone stimulated osteogenic osteoblast proliferation and differentiation in vitro and bone regeneration in vivo [42].”
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 [42]
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References 61 · Cited by 49
- Authors
- Yan, C.-P., Wang, X.-K., Jiang, K., Yin, C., Xiang, C., Wang, Y., Pu, C., Chen, L., & Li, Y.-L.
- Affiliations
- Affiliated Hospital of North Sichuan Medical College (CN)
- Northwestern Polytechnical University (CN)
- Corresponding author
- Jiang, Ke
- Li, Yu-Ling
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2022-05-20
- Volume
- 10
- Pages
- 883228-883228
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC9164109
- OpenAlex
- W4285741191
- Cited by
- 49
- References
- 61
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 11 · 2023: 13 · 2022: 1
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Sichuan Province Science and Technology Support Program (2021YJ0467)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
- Keywords
- bone regeneration, osteogenic differentiation, femoral condyle defect, bone defect repair, MC3T3-E1 cells, BMP-2, osteocalcin, collagen, bone mineral density
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