Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis

Abstract Nonsyndromic craniosynostosis (NSC) is the most common craniosynostosis with the primary defect being one or more fused sutures. In contrast to syndromic craniosynostosis, the etiopathogenesis of NSC is largely unknown. Here we show that autophagy, a major catabolic process required for the...

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Autores principales:	Shanshan Qiu, Jing Wang, Siqi Huang, Shouqing Sun, Zhen Zhang, Nan Bao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0103f64b043f49b086b6a5240d41b059
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spelling	oai:doaj.org-article:0103f64b043f49b086b6a5240d41b0592021-12-02T11:40:54ZOveractive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis10.1038/s41598-018-24885-z2045-2322https://doaj.org/article/0103f64b043f49b086b6a5240d41b0592018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24885-zhttps://doaj.org/toc/2045-2322Abstract Nonsyndromic craniosynostosis (NSC) is the most common craniosynostosis with the primary defect being one or more fused sutures. In contrast to syndromic craniosynostosis, the etiopathogenesis of NSC is largely unknown. Here we show that autophagy, a major catabolic process required for the maintenance of bone homeostasis and bone growth, is a pathological change associated with NSC. Using calvarial suture mesenchymal cells (SMCs) isolated from the fused and unfused sutures of NSC patients, we demonstrate that during SMC differentiation, the level of the autophagosomal marker LC3-II increases as osteogenic differentiation progresses, particularly at differentiation day 7, a stage concurrent with mineralization. In fused SMCs, autophagic induction was more robust than that in unfused SMCs, which consequently led to enhanced mineralized nodule formation. Perturbation of autophagy with rapamycin or wortmannin promoted or inhibited the ossification of SMCs, respectively. Our findings suggest that autophagy is essential for the osteogenic differentiation of SMCs and that overactive autophagy is a molecular abnormality underlying premature calvarial ossification in NSC.Shanshan QiuJing WangSiqi HuangShouqing SunZhen ZhangNan BaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shanshan Qiu Jing Wang Siqi Huang Shouqing Sun Zhen Zhang Nan Bao Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
description	Abstract Nonsyndromic craniosynostosis (NSC) is the most common craniosynostosis with the primary defect being one or more fused sutures. In contrast to syndromic craniosynostosis, the etiopathogenesis of NSC is largely unknown. Here we show that autophagy, a major catabolic process required for the maintenance of bone homeostasis and bone growth, is a pathological change associated with NSC. Using calvarial suture mesenchymal cells (SMCs) isolated from the fused and unfused sutures of NSC patients, we demonstrate that during SMC differentiation, the level of the autophagosomal marker LC3-II increases as osteogenic differentiation progresses, particularly at differentiation day 7, a stage concurrent with mineralization. In fused SMCs, autophagic induction was more robust than that in unfused SMCs, which consequently led to enhanced mineralized nodule formation. Perturbation of autophagy with rapamycin or wortmannin promoted or inhibited the ossification of SMCs, respectively. Our findings suggest that autophagy is essential for the osteogenic differentiation of SMCs and that overactive autophagy is a molecular abnormality underlying premature calvarial ossification in NSC.
format	article
author	Shanshan Qiu Jing Wang Siqi Huang Shouqing Sun Zhen Zhang Nan Bao
author_facet	Shanshan Qiu Jing Wang Siqi Huang Shouqing Sun Zhen Zhang Nan Bao
author_sort	Shanshan Qiu
title	Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
title_short	Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
title_full	Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
title_fullStr	Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
title_full_unstemmed	Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
title_sort	overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0103f64b043f49b086b6a5240d41b059
work_keys_str_mv	AT shanshanqiu overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis AT jingwang overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis AT siqihuang overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis AT shouqingsun overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis AT zhenzhang overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis AT nanbao overactiveautophagyisapathologicalmechanismunderlyingprematuresutureossificationinnonsyndromiccraniosynostosis
_version_	1718395499464097792

Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis

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