Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts

J Clin Invest. 1997 Nov 15;100(10):2476-85. doi: 10.1172/JCI119790.


Colony-stimulating factor-1 (CSF-1) stimulates motility and cytoplasmic spreading in mature osteoclasts. Therefore, we examined the cellular events and intracellular signaling pathways that accompany CSF-1-induced spreading in normal osteoclasts. To explore the role c-src plays in these processes, we also studied osteoclasts prepared from animals with targeted disruption of the src gene. In normal osteoclasts, CSF-1 treatment induces rapid cytoplasmic spreading, with redistribution of F-actin from a well-delineated central attachment ring to the periphery of the cell. CSF-1 increases membrane phosphotyrosine staining in osteoclasts and induces the phosphorylation of several cellular proteins in cultured, osteoclast-like cells, including c-fms, c-src, and an 85-kD Grb2-binding protein. Src kinase activity is increased threefold after CSF-1 treatment. In src- cells, no attachment ring is present, and CSF-1 fails to induce spreading or a change in the pattern of F-actin distribution. Although c-fms becomes phosphorylated after CSF-1 treatment, the 85-kD protein is significantly less phosphorylated in src- osteoclast-like cells. These results indicate that c-src is critical for the normal cytoskeletal architecture of the osteoclast, and, in its absence, the spreading response induced by CSF-1 is abrogated, and downstream signaling from c-fms is altered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Cell Movement / drug effects
  • Cells, Cultured
  • Cytoskeleton / drug effects
  • Cytoskeleton / ultrastructure*
  • Kinetics
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Molecular Sequence Data
  • Osteoclasts / drug effects
  • Osteoclasts / physiology*
  • Osteoclasts / ultrastructure
  • Peptides / chemistry
  • Peptides / metabolism
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins pp60(c-src) / deficiency
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Rats
  • Substrate Specificity
  • src-Family Kinases / metabolism*


  • Peptides
  • Phosphoproteins
  • Phosphotyrosine
  • Macrophage Colony-Stimulating Factor
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases