Expression of the Aryl Hydrocarbon Receptor in Growth Plate Cartilage and the Impact of Its Local Modulation on Longitudinal Bone Growth

International Journal of Molecular Sciences

Therése Cedervall²  Pia Monica Lind¹  Lars Sävendahl² 

[1] Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, 751 85 Uppsala, Sweden; E-Mail:;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; E-Mail:

关键词: AhR (aryl hydrocarbon receptor);    epiphyseal growth plate;    dioxin;    alpha-naphthoflavone;    chondrocyte;    bone growth;   

DOI  :  10.3390/ijms16048059

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.