Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain

Sayan Nandi, Mohammed P. Akhter, Mark F. Seifert, Xu Ming Dai, E. Richard Stanley

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The primary macrophage growth factor, colony-stimulating factor-1 (CSF-1), is homodimeric and exists in 3 biologically active isoforms: a membrane-spanning, cell-surface glycoprotein (csCSF-1) and secreted glycoprotein (sgCSF-1) and proteoglycan (spCSF-1) isoforms. To investigate the in vivo role of the chondroitin sulfate glycosaminoglycan (GAG) chain of spCSF-1, we created mice that exclusively express, in a normal tissue-specific and developmental manner, either the secreted precursor of spCSF-1 or the corresponding precursor in which the GAG addition site was mutated. The reproductive, hematopoietic tooth eruption and tissue macrophage defects of CSF-1-deficient, osteopetrotic Csf1op/Csf1op mice were corrected by transgenic expression of the precursors of either sgCSF-1 or spCSF-1. Furthermore, in contrast to the transgene encoding csCSF-1, both failed to completely correct growth retardation, suggesting a role for csCSF-1 in the regulation of body weight. However, spCSF-1, in contrast to sgCSF-1, completely resolved the osteopetrotic phenotype. Furthermore, in transgenic lines expressing different concentrations of sgCSF-1 or spCSF-1, spCSF-1 more efficiently corrected Csf1 op/Csf1op defects of tooth eruption, eyelid opening, macrophage morphology, and B-cell deficiency than sgCSF-1. These results indicate an important role of the CSF-1 chondroitin sulfate proteoglycan in in vivo signaling by secreted CSF-1.

Original languageEnglish
Pages (from-to)786-795
Number of pages10
JournalBlood
Volume107
Issue number2
DOIs
StatePublished - Jan 15 2006

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Chondroitin Sulfate Proteoglycans
Macrophage Colony-Stimulating Factor
Macrophages
Tooth Eruption
Protein Isoforms
Tissue
Defects
Membrane Glycoproteins
Proteoglycans
Glycosaminoglycans
Eyelids
Intercellular Signaling Peptides and Proteins
Glycoproteins
Transgenes
Cells
Membranes
B-Lymphocytes
Body Weight
Phenotype
Growth

All Science Journal Classification (ASJC) codes

  • Hematology

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Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. / Nandi, Sayan; Akhter, Mohammed P.; Seifert, Mark F.; Dai, Xu Ming; Stanley, E. Richard.

In: Blood, Vol. 107, No. 2, 15.01.2006, p. 786-795.

Research output: Contribution to journalArticle

Nandi, Sayan ; Akhter, Mohammed P. ; Seifert, Mark F. ; Dai, Xu Ming ; Stanley, E. Richard. / Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. In: Blood. 2006 ; Vol. 107, No. 2. pp. 786-795.
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