TY - JOUR
T1 - Administration of colony stimulating factor-1 corrects some macrophage, dental, and skeletal defects in an osteopetrotic mutation (toothless, tl) in the rat
AU - Marks, S. C.
AU - Wojtowicz, A.
AU - Szperl, M.
AU - Urbanowska, E.
AU - Mackay, C. A.
AU - Wiktor-Jedrzejczak, W.
AU - Stanley, E. R.
AU - Aukerman, S. L.
N1 - Funding Information:
Acknowledgmenrs: We thank M. Jackson, E. K. Larson, M. Cielinski, andR ezaZ adehf or superbt echnicaal ssistancea,n dE. C. Larson for typing the manuscript. These studies were supported by NIH Grants #DE 07444 (SCM), #CA 32551 (ERS), #P30-CA 1330 (ERS), and the Polish Committee for Scientific Research) (A.W., M.S., E.U.. W.W.J.)
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Colony Stimulating Factor-1 (CSF-1)
KW - Macrophage
KW - Macrophage-Colony Stimulating Factor (M-CSF)
KW - Osteoclast
KW - Osteopetrosis
KW - Rat
KW - Tooth eruption
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U2 - 10.1016/8756-3282(92)90365-4
DO - 10.1016/8756-3282(92)90365-4
M3 - Article
C2 - 1581113
AN - SCOPUS:0026608325
SN - 8756-3282
VL - 13
SP - 89
EP - 93
JO - Bone
JF - Bone
IS - 1
ER -