mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis
Journal article
Martin, Sally K., Fitter, Stephen, El Khawanky, Nadia, Grose, Randall H., Walkley, Carl, Purton, Louise E., Ruegg, Markus A., Hall, Michael N., Gronthos, Stan and Zannettino, Andrew C. W.. (2018). mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis. Scientific Reports. 8(1), pp. 1 - 10. https://doi.org/10.1038/s41598-018-32858-5
Authors | Martin, Sally K., Fitter, Stephen, El Khawanky, Nadia, Grose, Randall H., Walkley, Carl, Purton, Louise E., Ruegg, Markus A., Hall, Michael N., Gronthos, Stan and Zannettino, Andrew C. W. |
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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. |
Year | 2018 |
Journal | Scientific Reports |
Journal citation | 8 (1), pp. 1 - 10 |
Publisher | Nature Publishing Group |
ISSN | 2045-2322 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41598-018-32858-5 |
Scopus EID | 2-s2.0-85054056633 |
Open access | Open access |
Page range | 1 - 10 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | License |
Place of publication | United Kingdom |
https://acuresearchbank.acu.edu.au/item/86276/mtorc1-plays-an-important-role-in-osteoblastic-regulation-of-b-lymphopoiesis
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