Cargando…

Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway

OBJECTIVE: Chondrogenesis and endochondral ossification in mandibular condyle play crucial roles in maxillofacial morphogenesis and function. Circadian regulator brain and muscle arnt‐like 1 (BMAL1) is proven to be essential for embryonic and postnatal development. The goal of this study was to defi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Shaoling, Tang, Qingming, Xie, Mengru, Zhou, Xin, Long, Yanlin, Xie, Yanling, Guo, Fengyuan, Chen, Lili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985652/
https://www.ncbi.nlm.nih.gov/pubmed/31747713
http://dx.doi.org/10.1111/cpr.12727
_version_ 1783491850160570368
author Yu, Shaoling
Tang, Qingming
Xie, Mengru
Zhou, Xin
Long, Yanlin
Xie, Yanling
Guo, Fengyuan
Chen, Lili
author_facet Yu, Shaoling
Tang, Qingming
Xie, Mengru
Zhou, Xin
Long, Yanlin
Xie, Yanling
Guo, Fengyuan
Chen, Lili
author_sort Yu, Shaoling
collection PubMed
description OBJECTIVE: Chondrogenesis and endochondral ossification in mandibular condyle play crucial roles in maxillofacial morphogenesis and function. Circadian regulator brain and muscle arnt‐like 1 (BMAL1) is proven to be essential for embryonic and postnatal development. The goal of this study was to define the functions of BMAL1 in the embryonic and postnatal growth of mandibular condylar cartilages (MCC). MATERIALS AND METHODS: Micro‐CT, TUNEL staining and EdU assay were performed using BMAL1‐deficient mice model, and in vitro experiments were performed using rat chondrocytes isolated from MCC. RNA sequencing in mandibular condyle tissues from Bmal1 (‐/‐) mice and the age‐matched wild‐type mice was used for transcriptional profiling at different postnatal stages. RESULTS: The expression levels of BMAL1 decrease gradually in MCC. BMAL1 is proved to regulate sequential chondrocyte differentiation, and its deficiency can result in the impairment of endochondral ossification of MCC. RNA sequencing reveals hedgehog signalling pathway is the potential target of BMAL1. BMAL1 regulates hedgehog signalling and affects its downstream cascades through directly binding to the promoters of Ptch1 and Ihh, modulating targets of hedgehog signalling which is indispensable for endochondral ossification. Importantly, the short stature phenotypes caused by BMAL1 deficiency can be rescued by hedgehog signalling activator. CONCLUSIONS: Collectively, these results indicate that BMAL1 plays critical roles on chondrogenesis and endochondral ossification of MCC, giving a new insight on potential therapeutic strategies for facial dysmorphism.
format Online
Article
Text
id pubmed-6985652
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-69856522020-03-13 Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway Yu, Shaoling Tang, Qingming Xie, Mengru Zhou, Xin Long, Yanlin Xie, Yanling Guo, Fengyuan Chen, Lili Cell Prolif Original Articles OBJECTIVE: Chondrogenesis and endochondral ossification in mandibular condyle play crucial roles in maxillofacial morphogenesis and function. Circadian regulator brain and muscle arnt‐like 1 (BMAL1) is proven to be essential for embryonic and postnatal development. The goal of this study was to define the functions of BMAL1 in the embryonic and postnatal growth of mandibular condylar cartilages (MCC). MATERIALS AND METHODS: Micro‐CT, TUNEL staining and EdU assay were performed using BMAL1‐deficient mice model, and in vitro experiments were performed using rat chondrocytes isolated from MCC. RNA sequencing in mandibular condyle tissues from Bmal1 (‐/‐) mice and the age‐matched wild‐type mice was used for transcriptional profiling at different postnatal stages. RESULTS: The expression levels of BMAL1 decrease gradually in MCC. BMAL1 is proved to regulate sequential chondrocyte differentiation, and its deficiency can result in the impairment of endochondral ossification of MCC. RNA sequencing reveals hedgehog signalling pathway is the potential target of BMAL1. BMAL1 regulates hedgehog signalling and affects its downstream cascades through directly binding to the promoters of Ptch1 and Ihh, modulating targets of hedgehog signalling which is indispensable for endochondral ossification. Importantly, the short stature phenotypes caused by BMAL1 deficiency can be rescued by hedgehog signalling activator. CONCLUSIONS: Collectively, these results indicate that BMAL1 plays critical roles on chondrogenesis and endochondral ossification of MCC, giving a new insight on potential therapeutic strategies for facial dysmorphism. John Wiley and Sons Inc. 2019-11-20 /pmc/articles/PMC6985652/ /pubmed/31747713 http://dx.doi.org/10.1111/cpr.12727 Text en © 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yu, Shaoling
Tang, Qingming
Xie, Mengru
Zhou, Xin
Long, Yanlin
Xie, Yanling
Guo, Fengyuan
Chen, Lili
Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title_full Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title_fullStr Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title_full_unstemmed Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title_short Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
title_sort circadian bmal1 regulates mandibular condyle development by hedgehog pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985652/
https://www.ncbi.nlm.nih.gov/pubmed/31747713
http://dx.doi.org/10.1111/cpr.12727
work_keys_str_mv AT yushaoling circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT tangqingming circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT xiemengru circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT zhouxin circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT longyanlin circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT xieyanling circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT guofengyuan circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway
AT chenlili circadianbmal1regulatesmandibularcondyledevelopmentbyhedgehogpathway