Connective tissue growth factor is expressed in bone marrow stromal cells and promotes IL-7-dependent B lymphopoiesis
- Author(s)
- Cheung, LC; Strickland, DH; Howlett, M; Ford, J; Charles, AK; Lyons, KM; Brigstock, DR; Goldschmeding, R; Cole, CH; Alexander, WS; Kees, UR;
- Journal Title
- Haematologica
- Publication Type
- Journal Article
- Abstract
- Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells critically support the process via direct cell contact and 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 malignancy, 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 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 IL-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role in skeletogenesis and in stage-specific B lymphopoiesis.
- Publisher
- Ferrata Storti Foundation
- Keywords
- Bone Marrow Microenvironment, Hematopoiesis, Lymphocytes, Pediatric Acute Lymphoblastic Leukemia, lymphopoiesis
- Research Division(s)
- Cancer And Haematology
- Publisher's Version
- https://doi.org/10.3324/haematol.2013.102327
- Open Access at Publisher's Site
http://www.haematologica.org/content/early/2014/04/07/haematol.2013.102327.abstract- NHMRC Grants
- NHMRC/1016647,
- Terms of Use/Rights Notice
- Copyright © 2014, Ferrata Storti Foundation
Creation Date: 2014-05-22 07:46:39