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 hemat...

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Bibliographic Details
Published in:	Frontiers in cell and developmental biology Vol. 9; p. 718560
Main Authors:	Pissarra, Mariana Ferreira, Torello, Cristiane Okuda, Gomes, Rafael Gonçalves Barbosa, Shiraishi, Rodrigo Naoto, Santos, Irene, Vieira Ferro, Karla Priscila, Lopes, Matheus Rodrigues, Bergamo Favaro, Patricia Maria, Olalla Saad, Sara Teresinha, Lazarini, Mariana
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 30-11-2021
Subjects:	acute myeloid leukemia Cell and Developmental Biology myelodysplastic syndromes osteocalcin Rho GTPase RhoA RhoGAP acute myeloid leukemia RhoGAP myelodysplastic syndromes osteocalcin Cdc42 (cell division cycle 42 GTP-binding protein) Rho GTPase RhoA
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Summary:	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 , 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) and higher levels of osteocalcin were detected in the Arhgap21 BM supernatant. Increased expression of , and decreased expression of 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Matheus Rodrigues Lopes, Federal University of Vale do São Francisco, Paulo Afonso, Brazil Edited by: Aldo Roccaro, Civil Hospital of Brescia, Italy Eline Menu, Vrije University Brussel, Belgium This article was submitted to Stem Cell Research, a section of the journal Frontiers in Cell and Developmental Biology Reviewed by: Jo Caers, University of Liège, Belgium
ISSN:	2296-634X 2296-634X
DOI:	10.3389/fcell.2021.718560