Administration of colony stimulating factor-1 corrects some macrophage, dental, and skeletal defects in an osteopetrotic mutation (toothless, tl) in the rat

S. C. Marks, A. Wojtowicz, M. Szperl, E. Urbanowska, C. A. Mackay, W. Wiktor-Jedrzejczak, E. R. Stanley, S. L. Aukerman

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77 Scopus citations

Abstract

The toothless (tl/tl) mutation in the rat results in a paucity of osteoclasts and osteopetrosis that cannot be corrected by bone marrow transplantation. In the present study we demonstrate that tl/tl rats also have profound deficiencies of femoral, peritoneal, and pleural cavity macrophages. Further-more, the macrophage colony stimulating activity of post-endotoxin sera from tl/tl rats is substantially reduced, suggesting that, as in the case of the op mutation in mice, the basis of the tl mutation is a deficiency of the macrophage growth factor, colony stimulating factor-1 (CSF-1). Consistent with this suggestion, treatment of tl/tl rats from birth for up to six weeks with CSF-1 reduced the osteopetrosis, increased body weight, and permitted tooth eruption. In addition, CSF-1 treatment induced large numbers of osteoclasts in tl/tl bones and macrophages in the peritoneal cavity and bone marrow. Persistence of metaphyseal sclerosis, however, indicated that the disease was not totally corrected by this treatment. These studies indicate that the basis of the tl mutation is most likely another CSF-1 deficiency, and further emphasize the role of this growth factor in osteoclast differentiation.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalBone
Volume13
Issue number1
DOIs
StatePublished - 1992

Keywords

  • Colony Stimulating Factor-1 (CSF-1)
  • Macrophage
  • Macrophage-Colony Stimulating Factor (M-CSF)
  • Osteoclast
  • Osteopetrosis
  • Rat
  • Tooth eruption

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Marks, S. C., Wojtowicz, A., Szperl, M., Urbanowska, E., Mackay, C. A., Wiktor-Jedrzejczak, W., Stanley, E. R., & Aukerman, S. L. (1992). Administration of colony stimulating factor-1 corrects some macrophage, dental, and skeletal defects in an osteopetrotic mutation (toothless, tl) in the rat. Bone, 13(1), 89-93. https://doi.org/10.1016/8756-3282(92)90365-4