Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor.
Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor.
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DOI：
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发表时间：
1991-11
影响因子：
2.6
通讯作者：
W. Wiktor-Jedrzejczak;E. Urbanowska;S. L. Aukerman;J. Pollard;E. Stanley;P. Ralph;A. Ansari;K. Sell
中科院分区：
文献类型：
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作者：
W. Wiktor-Jedrzejczak;E. Urbanowska;S. L. Aukerman;J. Pollard;E. Stanley;P. Ralph;A. Ansari;K. Sell
由于CSF-1（巨噬细胞集落刺激因子，M-CSF）基因的失活突变，op基因突变的小鼠严重缺乏单核吞噬细胞。OP/OP小鼠无牙，具有骨骼异常、低体重和受损的生育能力;它们由于破骨细胞的缺乏而患骨硬化症。通过维持正常循环CSF-1浓度的人重组CSF-1给药途径纠正先天性骨硬化症、无牙表型、破骨细胞缺陷以及脾和股骨巨噬细胞缺陷。需要早期恢复循环CSF-1以挽救无牙表型，但仅部分恢复体重。相比之下，胸膜和腹腔巨噬细胞的缺陷和女性生育能力的降低并没有通过恢复循环CSF-1来纠正。这些结果表明，尽管循环CSF-1是破骨细胞和巨噬细胞产生所必需的，但生长因子的局部合成和作用对于某些靶细胞群体是重要的。
Mice that are mutant at the op locus have a severe deficiency of mononuclear phagocytes due to an inactivating mutation in the CSF-1 (macrophage colony-stimulating factor, M-CSF) gene. op/op mice are toothless, possessing skeletal abnormalities, a low body weight, and compromised fertility; they are osteopetrotic due to a deficiency of osteoclasts. The congenital osteopetrosis, toothless phenotype, osteoclast deficit, and the defects in splenic and femoral macrophages were corrected by routes of administration of human recombinant CSF-1 that maintained normal circulating CSF-1 concentrations. Early restoration of circulating CSF-1 was required for rescue of the toothless phenotype, but only partially restored body weight. In contrast, the deficiencies of pleural and peritoneal cavity macrophages and the reduced female fertility were not corrected by restoration of circulating CSF-1. These results suggest that although circulating CSF-1 is required for osteoclast and macrophage production, local synthesis and action of the growth factor are important for certain target cell populations.