Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known...

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Main Authors: Cheung, Laurence, Strickland, D., Howlett, M., Ford, J., Charles, A., Lyons, K., Brigstock, D., Goldschmeding, R., Cole, C., Alexander, W., Kees, U.
Format: Journal Article
Published: Ferrata Storti Foundation 2014
Online Access:http://hdl.handle.net/20.500.11937/59563
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author Cheung, Laurence
Strickland, D.
Howlett, M.
Ford, J.
Charles, A.
Lyons, K.
Brigstock, D.
Goldschmeding, R.
Cole, C.
Alexander, W.
Kees, U.
author_facet Cheung, Laurence
Strickland, D.
Howlett, M.
Ford, J.
Charles, A.
Lyons, K.
Brigstock, D.
Goldschmeding, R.
Cole, C.
Alexander, W.
Kees, U.
author_sort Cheung, Laurence
building Curtin Institutional Repository
collection Online Access
description Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis.
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institution Curtin University Malaysia
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spelling curtin-20.500.11937-595632018-03-29T02:50:03Z Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis Cheung, Laurence Strickland, D. Howlett, M. Ford, J. Charles, A. Lyons, K. Brigstock, D. Goldschmeding, R. Cole, C. Alexander, W. Kees, U. Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. 2014 Journal Article http://hdl.handle.net/20.500.11937/59563 10.3324/haematol.2013.102327 Ferrata Storti Foundation unknown
spellingShingle Cheung, Laurence
Strickland, D.
Howlett, M.
Ford, J.
Charles, A.
Lyons, K.
Brigstock, D.
Goldschmeding, R.
Cole, C.
Alexander, W.
Kees, U.
Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title_full Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title_fullStr Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title_full_unstemmed Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title_short Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
title_sort connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent b lymphopoiesis
url http://hdl.handle.net/20.500.11937/59563