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Glycosaminoglycans bind granulocyte‐macrophage colony‐stimulating factor and modulate its mitogenic activity and signaling in human osteoblastic cells
Author(s) -
Modrowski Dominique,
Lomri Abderrahim,
Marie Pierre J.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199810)177:1<187::aid-jcp19>3.0.co;2-a
Subject(s) - autocrine signalling , glycosaminoglycan , microbiology and biotechnology , cell growth , growth factor , biology , paracrine signalling , signal transduction , granulocyte macrophage colony stimulating factor , cell culture , extracellular matrix , chemistry , biochemistry , receptor , in vitro , genetics
We recently demonstrated that granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is an autocrine growth factor for human osteoblastic (hOB) cells. Since GM‐CSF is a member of the heparin‐binding factor family, we examined the interactions between GM‐CSF and glycosaminoglycans (GAGs) present in the osteoblast microenvironment. Using a bioassay in which the mitogenic activity of recombinant human (rh) GM‐CSF was measured after incubation in the presence of an hOB cell layer or extracellular matrix (ECM) produced by these cells, we showed that rhGM‐CSF binds to GAG components present in the ECM and that the bound rhGM‐CSF retains its ability to stimulate hOB cell proliferation. Heparan sulfate compounds on the hOB cell surface were also found to sequester GM‐CSF. Moreover, treatment with sodium chlorate, an inhibitor of GAG sulfation, suppressed the mitogenic activity of rhGM‐CSF on hOB cells. This inhibitory effect was rescued by a low dose of heparin. Heparin was also found to promote the effect of rhGM‐CSF on hOB cell proliferation, allowing nonmitogenic high doses of rhGM‐CSF to stimulate hOB cell growth. Western blot analysis showed that undersulfation of cellular GAGs by chlorate inhibited the increased tyrosine phosphorylation of proteins involved in GM‐CSF signaling in cloned immortalized hOB cells. The data demonstrate that GM‐CSF binds to proteoglycans on the hOB cell surface and in ECM produced by these cells and that the bound GM‐CSF is biologically active. Furthermore, this study shows that cellular proteoglycans play an essential role in GM‐CSF signaling and biological activity in hOBs. J. Cell. Physiol. 177:187–195, 1998. © 1998 Wiley‐Liss, Inc.