Premium
Defining Molecular Mechanisms for Osteoblast Function in the Hematopoietic Stem Cell (HSC) Niche
Author(s) -
Streitz Lisa
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a253
Subject(s) - osteopontin , microbiology and biotechnology , motility , osteoblast , stem cell , haematopoiesis , hematopoietic stem cell , population , integrin , bone marrow , biology , cell , chemistry , immunology , biochemistry , medicine , in vitro , environmental health
Osteoblasts are important in maintaining HSC, since mutant mice with elevated numbers of osteoblasts display increases in HSC. Preliminary evidence suggests osteoblasts also recirculate along with HSC in order to support their function at extramedullary sites. The purpose of this research was to identify and understand the molecular mechanisms which regulate osteoblast mediated induction of increased HSC cell motility. Osteoblasts were isolated from bone, blood and spleen and by means of FACS, analyzed based on frequency cells double positive for the αβ dimer. Decreases were seen in the frequency of OSBS expressing the integrin dimer α4β1, which functions in cell motility, in the bone during cytokine induced HSC mobilization. In contrast, increases were seen in the frequency of this population in the blood and spleen suggesting the possibility that only the α4β1+ OSBs can circulate and that this subpopulation preferentially plays a role in HSC migration to peripheral sites. This may also suggests that an attachment within the niche needs to be released for the HSC to move into extramedullary sites. Changes in soluble mediators, specifically soluble osteopontin were assessed. An increase in levels of secreted Opn in OSB/HSC co‐cultures were seen. Soluble Opn is thought to play a role in cell motility and thus may suggest that OSBs mediate HSC migration a cell‐cell contact dependent and independent manner.