title: Expression of vascular endothelial growth factor in the growth plate is stimulated by estradiol and increases during pubertal development.
abstract: 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.
authors.affiliation: Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands. j.emons@lumc.nl
authors.forename: Joyce
authors.initials: J
authors.lastname: Emons
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Chagin
authors.forename: Torun
authors.initials: T
authors.lastname: Malmlöf
authors.forename: Magnus
authors.initials: M
authors.lastname: Lekman
authors.forename: Asa
authors.initials: A
authors.lastname: Tivesten
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
mesh_terms: D000293:Adolescent; D000375:Aging / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002648:Child; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D023421:Models, Animal; D011627:Puberty / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol