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J Craniomaxillofac Surg. 2014 Jan;42(1):1-6. doi: 10.1016/j.jcms.2013.01.024. Epub 2013 Apr 17.

TCDD disrupts posterior palatogenesis and causes cleft palate.

Author information

1
Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan. Electronic address: tyamada@kochi-u.ac.jp.
2
Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College (Head: Prof. Yoshinori Otsuki), 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
3
Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.

Abstract

Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate. A post-fusional split may contribute to the pathogenesis, and tissue fragility may be a concern. The objective of this study was to investigate the effects of TCDD on the palatal epithelium, bone and muscle, which contribute to tissue integrity. ICR mice (10-12 weeks old) were used. TCDD was administered on E12.5 at 40 mg/kg. Immunohistochemical staining for AhR, ER-α, laminin, collagen IV, osteopontin, Runx2, MyoD, and desmin were performed. Furthermore, western blot analysis for osteopontin, Runx2, MyoD, and desmin were performed to evaluate protein expression in the palatal tissue. Immunohistologically, there was little difference in the collagen IV and laminin localization in the palatal epithelium between control versus TCDD-treated mice. Runx2 and osteopontin immunoreactivity decreased in the TCDD-treated palatal bone, and MyoD and desmin decreased in the TCDD-treated palatal muscle. AhR and ER-α immunoreactivity were localized to the normal palatal bone, but ER-α was diminished in the TCDD-treated palate. On western blot analysis, Runx2, MyoD, and desmin were all downregulated in the TCDD-treated palate. TCDD may suppress palatal osteogenesis and myogenesis via AhR, and cause cleft palates via a post-fusional split mechanism, in addition to a failure of palatal fusion.

KEYWORDS:

Cleft palate; Myogenesis; Osteogenesis; Post-fusional split; Posterior palate; TCDD

PMID:
23602632
DOI:
10.1016/j.jcms.2013.01.024
[Indexed for MEDLINE]
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