Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis

Abstract In vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF...

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Autores principales:	Wei Jiang, Nobuo Takeshita, Toshihiro Maeda, Chisumi Sogi, Toshihito Oyanagi, Seiji Kimura, Michiko Yoshida, Kiyo Sasaki, Arata Ito, Teruko Takano-Yamamoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/151c0e7d446247ac856f8c25541f48b1
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spelling	oai:doaj.org-article:151c0e7d446247ac856f8c25541f48b12021-12-02T14:16:07ZConnective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis10.1038/s41598-021-82246-92045-2322https://doaj.org/article/151c0e7d446247ac856f8c25541f48b12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82246-9https://doaj.org/toc/2045-2322Abstract In vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF) is known to exert chemotactic properties on various cells; however, details of CTGF function in the chemotaxis of osteoblast lineage cells and underlying molecular biological mechanisms have not been clarified. The aim of the present study was to evaluate the chemotactic properties of CTGF and its underlying mechanisms during active bone formation through intramembranous osteogenesis. In our mouse tensile force-induced bone formation model, preosteoblasts were aggregated at the osteogenic front of calvarial bones. CTGF was expressed at the osteogenic front, and functional inhibition of CTGF using a neutralizing antibody suppressed the aggregation of preosteoblasts. In vitro experiments using μ-slide chemotaxis chambers showed that a gradient of CTGF induced chemotaxis of preosteoblastic MC3T3-E1 cells, while a neutralizing integrin α5 antibody and a Ras inhibitor inhibited the CTGF-induced chemotaxis of MC3T3-E1 cells. These findings suggest that the CTGF-integrin α5-Ras axis is an essential molecular mechanism to promote chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis.Wei JiangNobuo TakeshitaToshihiro MaedaChisumi SogiToshihito OyanagiSeiji KimuraMichiko YoshidaKiyo SasakiArata ItoTeruko Takano-YamamotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei Jiang Nobuo Takeshita Toshihiro Maeda Chisumi Sogi Toshihito Oyanagi Seiji Kimura Michiko Yoshida Kiyo Sasaki Arata Ito Teruko Takano-Yamamoto Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
description	Abstract In vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF) is known to exert chemotactic properties on various cells; however, details of CTGF function in the chemotaxis of osteoblast lineage cells and underlying molecular biological mechanisms have not been clarified. The aim of the present study was to evaluate the chemotactic properties of CTGF and its underlying mechanisms during active bone formation through intramembranous osteogenesis. In our mouse tensile force-induced bone formation model, preosteoblasts were aggregated at the osteogenic front of calvarial bones. CTGF was expressed at the osteogenic front, and functional inhibition of CTGF using a neutralizing antibody suppressed the aggregation of preosteoblasts. In vitro experiments using μ-slide chemotaxis chambers showed that a gradient of CTGF induced chemotaxis of preosteoblastic MC3T3-E1 cells, while a neutralizing integrin α5 antibody and a Ras inhibitor inhibited the CTGF-induced chemotaxis of MC3T3-E1 cells. These findings suggest that the CTGF-integrin α5-Ras axis is an essential molecular mechanism to promote chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis.
format	article
author	Wei Jiang Nobuo Takeshita Toshihiro Maeda Chisumi Sogi Toshihito Oyanagi Seiji Kimura Michiko Yoshida Kiyo Sasaki Arata Ito Teruko Takano-Yamamoto
author_facet	Wei Jiang Nobuo Takeshita Toshihiro Maeda Chisumi Sogi Toshihito Oyanagi Seiji Kimura Michiko Yoshida Kiyo Sasaki Arata Ito Teruko Takano-Yamamoto
author_sort	Wei Jiang
title	Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
title_short	Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
title_full	Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
title_fullStr	Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
title_full_unstemmed	Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
title_sort	connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and ras during tensile force-induced intramembranous osteogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/151c0e7d446247ac856f8c25541f48b1
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Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis

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