Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A

Abstract Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, increases osteoblast differentiation, stimulates bone formation and enhances fracture healing. Here, we report a previously unknown role of Sema3A in the regulation of ectopic bone formation and osteolysis related to osteos...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daniëlle de Ridder, Silvia Marino, Ryan T. Bishop, Nathalie Renema, Chantal Chenu, Dominique Heymann, Aymen I. Idris
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/994150735f414fcf99e03f4cca7c2b49
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:994150735f414fcf99e03f4cca7c2b49
record_format	dspace
spelling	oai:doaj.org-article:994150735f414fcf99e03f4cca7c2b492021-12-02T15:08:22ZBidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A10.1038/s41598-018-25290-22045-2322https://doaj.org/article/994150735f414fcf99e03f4cca7c2b492018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25290-2https://doaj.org/toc/2045-2322Abstract Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, increases osteoblast differentiation, stimulates bone formation and enhances fracture healing. Here, we report a previously unknown role of Sema3A in the regulation of ectopic bone formation and osteolysis related to osteosarcoma. Human recombinant (exogenous) Sema3A promoted the expression of osteoblastic phenotype in a panel of human osteosarcoma cell lines and inhibited the ability of these cells to migrate and enhance osteoclastogenesis in vitro. In vivo, administration of exogenous Sema3A in mice after paratibial inoculation of KHOS cells increased bone volume in non-inoculated and tumour-bearing legs. In contrast, Sema3A overexpression reduced the ability of KHOS cells to cause ectopic bone formation in mice and to increase bone nodule formation by engaging DKK1/β-catenin signalling. Thus, Sema3A is of potential therapeutic efficacy in osteosarcoma. However, inhibition of bone formation associated with continuous exposure to Sema3A may limit its long-term usefulness as therapeutic agent.Daniëlle de RidderSilvia MarinoRyan T. BishopNathalie RenemaChantal ChenuDominique HeymannAymen I. IdrisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniëlle de Ridder Silvia Marino Ryan T. Bishop Nathalie Renema Chantal Chenu Dominique Heymann Aymen I. Idris Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
description	Abstract Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, increases osteoblast differentiation, stimulates bone formation and enhances fracture healing. Here, we report a previously unknown role of Sema3A in the regulation of ectopic bone formation and osteolysis related to osteosarcoma. Human recombinant (exogenous) Sema3A promoted the expression of osteoblastic phenotype in a panel of human osteosarcoma cell lines and inhibited the ability of these cells to migrate and enhance osteoclastogenesis in vitro. In vivo, administration of exogenous Sema3A in mice after paratibial inoculation of KHOS cells increased bone volume in non-inoculated and tumour-bearing legs. In contrast, Sema3A overexpression reduced the ability of KHOS cells to cause ectopic bone formation in mice and to increase bone nodule formation by engaging DKK1/β-catenin signalling. Thus, Sema3A is of potential therapeutic efficacy in osteosarcoma. However, inhibition of bone formation associated with continuous exposure to Sema3A may limit its long-term usefulness as therapeutic agent.
format	article
author	Daniëlle de Ridder Silvia Marino Ryan T. Bishop Nathalie Renema Chantal Chenu Dominique Heymann Aymen I. Idris
author_facet	Daniëlle de Ridder Silvia Marino Ryan T. Bishop Nathalie Renema Chantal Chenu Dominique Heymann Aymen I. Idris
author_sort	Daniëlle de Ridder
title	Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
title_short	Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
title_full	Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
title_fullStr	Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
title_full_unstemmed	Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
title_sort	bidirectional regulation of bone formation by exogenous and osteosarcoma-derived sema3a
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/994150735f414fcf99e03f4cca7c2b49
work_keys_str_mv	AT daniellederidder bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT silviamarino bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT ryantbishop bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT nathalierenema bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT chantalchenu bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT dominiqueheymann bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a AT aymeniidris bidirectionalregulationofboneformationbyexogenousandosteosarcomaderivedsema3a
_version_	1718388202035740672

Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A

Ejemplares similares