Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment

ARHGAP21 is a member of the RhoGAP family of proteins involved in cell growth, differentiation, and adhesion. We have previously shown that the heterozygous Arhgap21 knockout mouse model (Arhgap21+/−) presents several alterations in the hematopoietic compartment, including increased frequency of hem...

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Autores principales:	Mariana Ferreira Pissarra, Cristiane Okuda Torello, Rafael Gonçalves Barbosa Gomes, Rodrigo Naoto Shiraishi, Irene Santos, Karla Priscila Vieira Ferro, Matheus Rodrigues Lopes, Patricia Maria Bergamo Favaro, Sara Teresinha Olalla Saad, Mariana Lazarini
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	osteocalcin myelodysplastic syndromes acute myeloid leukemia RhoGAP Rho GTPase RhoA Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f1b339ee32af4665bb0f5d054c68e215
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spelling	oai:doaj.org-article:f1b339ee32af4665bb0f5d054c68e2152021-12-01T19:13:38ZArhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment2296-634X10.3389/fcell.2021.718560https://doaj.org/article/f1b339ee32af4665bb0f5d054c68e2152021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.718560/fullhttps://doaj.org/toc/2296-634XARHGAP21 is a member of the RhoGAP family of proteins involved in cell growth, differentiation, and adhesion. We have previously shown that the heterozygous Arhgap21 knockout mouse model (Arhgap21+/−) presents several alterations in the hematopoietic compartment, including increased frequency of hematopoietic stem and progenitor cells (HSPC) with impaired adhesion in vitro, increased mobilization to peripheral blood, and decreased engraftment after bone marrow transplantation. Although these HSPC functions strongly depend on their interactions with the components of the bone marrow (BM) niche, the role of ARHGAP21 in the marrow microenvironment has not yet been explored. In this study, we investigated the composition and function of the BM microenvironment in Arhgap21+/− mice. The BM of Arhgap21+/− mice presented a significant increase in the frequency of phenotypic osteoblastic lineage cells, with no differences in the frequencies of multipotent stromal cells or endothelial cells when compared to the BM of wild type mice. Arhgap21+/− BM cells had increased capacity of generating osteogenic colony-forming units (CFU-OB) in vitro and higher levels of osteocalcin were detected in the Arhgap21+/− BM supernatant. Increased expression of Col1a1, Ocn and decreased expression of Trap1 were observed after osteogenic differentiation of Arhgap21+/− BM cells. In addition, Arhgap21+/− mice recipients of normal BM cells showed decreased leucocyte numbers during transplantation recovery. Our data suggest participation of ARHGAP21 in the balanced composition of the BM microenvironment through the regulation of osteogenic differentiation.Mariana Ferreira PissarraCristiane Okuda TorelloRafael Gonçalves Barbosa GomesRodrigo Naoto ShiraishiIrene SantosKarla Priscila Vieira FerroMatheus Rodrigues LopesPatricia Maria Bergamo FavaroPatricia Maria Bergamo FavaroSara Teresinha Olalla SaadMariana LazariniMariana LazariniFrontiers Media S.A.articleosteocalcinmyelodysplastic syndromesacute myeloid leukemiaRhoGAPRho GTPaseRhoABiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteocalcin myelodysplastic syndromes acute myeloid leukemia RhoGAP Rho GTPase RhoA Biology (General) QH301-705.5
spellingShingle	osteocalcin myelodysplastic syndromes acute myeloid leukemia RhoGAP Rho GTPase RhoA Biology (General) QH301-705.5 Mariana Ferreira Pissarra Cristiane Okuda Torello Rafael Gonçalves Barbosa Gomes Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Vieira Ferro Matheus Rodrigues Lopes Patricia Maria Bergamo Favaro Patricia Maria Bergamo Favaro Sara Teresinha Olalla Saad Mariana Lazarini Mariana Lazarini Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
description	ARHGAP21 is a member of the RhoGAP family of proteins involved in cell growth, differentiation, and adhesion. We have previously shown that the heterozygous Arhgap21 knockout mouse model (Arhgap21+/−) presents several alterations in the hematopoietic compartment, including increased frequency of hematopoietic stem and progenitor cells (HSPC) with impaired adhesion in vitro, increased mobilization to peripheral blood, and decreased engraftment after bone marrow transplantation. Although these HSPC functions strongly depend on their interactions with the components of the bone marrow (BM) niche, the role of ARHGAP21 in the marrow microenvironment has not yet been explored. In this study, we investigated the composition and function of the BM microenvironment in Arhgap21+/− mice. The BM of Arhgap21+/− mice presented a significant increase in the frequency of phenotypic osteoblastic lineage cells, with no differences in the frequencies of multipotent stromal cells or endothelial cells when compared to the BM of wild type mice. Arhgap21+/− BM cells had increased capacity of generating osteogenic colony-forming units (CFU-OB) in vitro and higher levels of osteocalcin were detected in the Arhgap21+/− BM supernatant. Increased expression of Col1a1, Ocn and decreased expression of Trap1 were observed after osteogenic differentiation of Arhgap21+/− BM cells. In addition, Arhgap21+/− mice recipients of normal BM cells showed decreased leucocyte numbers during transplantation recovery. Our data suggest participation of ARHGAP21 in the balanced composition of the BM microenvironment through the regulation of osteogenic differentiation.
format	article
author	Mariana Ferreira Pissarra Cristiane Okuda Torello Rafael Gonçalves Barbosa Gomes Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Vieira Ferro Matheus Rodrigues Lopes Patricia Maria Bergamo Favaro Patricia Maria Bergamo Favaro Sara Teresinha Olalla Saad Mariana Lazarini Mariana Lazarini
author_facet	Mariana Ferreira Pissarra Cristiane Okuda Torello Rafael Gonçalves Barbosa Gomes Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Vieira Ferro Matheus Rodrigues Lopes Patricia Maria Bergamo Favaro Patricia Maria Bergamo Favaro Sara Teresinha Olalla Saad Mariana Lazarini Mariana Lazarini
author_sort	Mariana Ferreira Pissarra
title	Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
title_short	Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
title_full	Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
title_fullStr	Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
title_full_unstemmed	Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
title_sort	arhgap21 deficiency results in increase of osteoblastic lineage cells in the murine bone marrow microenvironment
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f1b339ee32af4665bb0f5d054c68e215
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Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment

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