Expression of vascular endothelial growth factor in the growth plate is stimulated by estradiol and increases during pubertal development
Open accessAbstract
Longitudinal bone growth is regulated in the growth plate. At the end of puberty, growth velocity diminishes and eventually ceases with the fusion of the growth plate through mechanisms that are not yet completely understood. Vascular endothelial growth factor (VEGF) has an important role in angiogenesis, but also in chondrocyte differentiation, chondrocyte survival, and the final stages of endochondral ossification. Estrogens have been shown to up-regulate VEGF expression in the uterus and bone of rats. In this study, we investigated the relation between estrogens and VEGF production in growth plate chondrocytes both in vivo and in vitro . The expression of VEGF protein was down-regulated upon ovariectomy and was restored upon estradiol (E 2 ) supplementation in rat growth plates. In cultured rat chondrocyte cell line RCJ3.1C5.18, E 2 dose dependently stimulated 121 and 189 kDa isoforms of VEGF, but not the 164 kDa isoform. Finally, VEGF expression was observed at both protein and mRNA levels in human growth plate specimens. The protein level increased during pubertal development, supporting a link between estrogens and local VEGF production in the growth plate. We conclude that estrogens regulate VEGF expression in the epiphyseal growth plate, although the precise role of VEGF in estrogen-mediated growth plate fusion remains to be clarified.
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In growth from child to adult, serum albumin concentration is normal but low rising to adult normal, and VEGF is increased.
“Growth from child to adult | N ↓ rising to adult N | NA | NA | NA | NA | NA | ↑37, 38 , 161 | Connectivity VEGF gene‐metabolic pathway stronger in children”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [38]
The ‘VEGF protein and mRNA expressions in human growth plates’ section reports significantly increased VEGF protein expression with pubertal progression in girls’ growth plates. That supports the cited VEGF increase during puberty, but not an unqualified increase across growth from childhood to adulthood. The serum-albumin entry is a separate table column and is not attributed to this citation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredVEGF expression and increased vascular permeability occur in infection, trauma, during fetal and postnatal growth, preparing for lactation, cancer, protein-losing enteropathy, and nephrotic syndrome.
“VEGF expression and increased vascular permeability occur in infection,14, 35 trauma,15, 16, 36 during fetal and postnatal growth,29, 37, 38, 39 preparing for lactation,39, 40 cancer,41, 42 protein‐losing enteropathy,43 and nephrotic syndrome44, 45 (Table 1).”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [38]
The section on VEGF protein and mRNA expression in human growth plates reports VEGF expression in fetal and pubertal growth plates, supporting the fetal and postnatal growth portion of the claim. It does not report increased vascular permeability during those stages. No page number is available in our copy. (LLM, conf=0.86)
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Cites
Metzger, D. L., & Kerrigan, J. R. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.2.8045971 · Cited by 152 · see citing works
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Research works printed but not linked: 14
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Hypoalbuminemia: Pathogenesis and Clinical Significance
Soeters, P. B., Wolfe, R. R., & Shenkin, A. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1451 · Cited by 1,448 · see citing works
- Authors
- Emons, J., Chagin, A. S., Malmlöf, T., Lekman, M., Tivesten, Å., Ohlsson, C., Wit, J. M., Karperien, M., & Sävendahl, L.
- Affiliations
- Leiden University Medical Center (NL)
- Karolinska Institutet (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Emons, Joyce
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2010-01-19
- Volume
- 205
- Issue
- 1
- Pages
- 61-68
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2159133954
- Cited by
- 25
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2018: 1 · 2016: 3 · 2015: 1 · 2013: 1 · 2012: 4
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- University of Twente Research Information (submittedVersion)
- European Journal of Endocrinology
- Funders
- European Society for Paediatric Endocrinology
- Universiteit Leiden
- ZonMw
- Vetenskapsrådet
- Leids Universitair Medisch Centrum
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- vascular endothelial growth factor, growth plate, estradiol, estrogen, puberty, chondrocytes, ovariectomy, VEGF isoforms, endochondral ossification, epiphyseal fusion, longitudinal bone growth, angiogenesis
- MeSH terms
- Adolescent, Aging, Animals, Cell Line, Child, Estradiol, Female, Growth Plate, Humans, Puberty, RNA, Messenger, Sexual Maturation, Rats, Sprague-Dawley, Chondrocytes, Models, Animal, Vascular Endothelial Growth Factor A, Rats
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