Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/117691
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Type: Journal article
Title: mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis
Author: Martin, S.
Fitter, S.
El Khawanky, N.
Grose, R.
Walkley, C.
Purton, L.
Ruegg, M.
Hall, M.
Gronthos, S.
Zannettino, A.
Citation: Scientific Reports, 2018; 8(1):14501-1-14501-10
Publisher: Springer Nature
Issue Date: 2018
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Sally K. Martin, Stephen Fitter, Nadia El Khawanky, Randall H. Grose, Carl R. Walkley, Louise E. Purton, Markus A. Ruegg, Michael N. Hall, Stan Gronthos, Andrew C.W. Zannettino
Abstract: Skeletal osteoblasts are important regulators of B-lymphopoiesis, serving as a rich source of factors such as CXCL12 and IL-7 which are crucial for B-cell development. Recent studies from our laboratory and others have shown that deletion of Rptor, a unique component of the mTORC1 nutrient-sensing complex, early in the osteoblast lineage development results in defective bone development in mice. In this study, we now demonstrate that mTORC1 signalling in pre-osteoblasts is required for normal B-lymphocyte development in mice. Targeted deletion of Rptor in osterix-expressing pre-osteoblasts (Rptorob-/-) leads to a significant reduction in the number of B-cells in the bone marrow, peripheral blood and spleen at 4 and 12 weeks of age. Rptorob-/- mice also exhibit a significant reduction in pre-B and immature B-cells in the BM, indicative of a block in B-cell development from the pro-B to pre-B cell stage. Circulating levels of IL-7 and CXCL12 are also significantly reduced in Rptorob-/- mice. Importantly, whilst Rptor-deficient osteoblasts are unable to support HSC differentiation to B-cells in co-culture, this can be rescued by the addition of exogenous IL-7 and CXCL12. Collectively, these findings demonstrate that mTORC1 plays an important role in extrinsic osteoblastic regulation of B-cell development.
Keywords: B-Lymphocytes
Osteoblasts
Animals
Mice, Transgenic
Mice, Knockout
Mice
RNA, Messenger
Interleukin-7
Coculture Techniques
Lymphopoiesis
Down-Regulation
Genes, Reporter
Chemokine CXCL12
Sp7 Transcription Factor
Mechanistic Target of Rapamycin Complex 1
Regulatory-Associated Protein of mTOR
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI: 10.1038/s41598-018-32858-5
Grant ID: http://purl.org/au-research/grants/nhmrc/1030528
Appears in Collections:Aurora harvest 3
Medicine publications

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