title: Expression of the aryl hydrocarbon receptor in growth plate cartilage and the impact of its local modulation on longitudinal bone growth.
abstract: Although dioxin has been reported to impair bone growth in both humans and animals, the underlying mechanisms have not been clarified. We conducted this study to rule out if dioxin may directly target the growth plate, via local modulation of the aryl hydrocarbon receptor (AhR). Initial studies in rare tissue samples of the human growth plate confirmed that the AhR protein is widely expressed in growth plate cartilage. To explore the local role of the AhR, mechanistic studies were performed in a well-established model of cultured fetal rat metatarsal bones. The longitudinal growth of these bones was monitored while being exposed to AhR modulators. The AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin, did not affect bone growth at any concentrations tested (1 pM-10 nM). In contrast, the AhR antagonist, alpha-naphthoflavone, suppressed bone growth and increased chondrocyte apoptosis, although only at a high, potentially cytotoxic concentration (50 µM). We conclude that although the AhR is widely expressed in the growth plate, bone growth is not modulated when locally activated, and therefore, dioxin-induced growth failure is likely mediated through systemic rather than local actions.
authors: Department of Women's and Children's Health, Pediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Q2:08, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. therese.cedervall@ki.se.
authors: Therése
authors: T
authors: Cedervall
authors: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, 751 85 Uppsala, Sweden. monica.lind@medsci.uu.se.
authors: Pia Monica
authors: PM
authors: Lind
authors: Department of Women's and Children's Health, Pediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Q2:08, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. lars.savendahl@ki.se.
authors: Lars
authors: L
authors: Sävendahl
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001571:Benzoflavones / Q000494:pharmacology; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology; D005260:Female; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D001571:Benzoflavones; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C011512:alpha-naphthoflavone