Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor.

Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor.
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先天性破骨细胞的骨质术(OP/OP)小鼠的缺乏通过注射巨噬细胞刺激因子的注射来治愈。

DOI:
10.1084/jem.173.1.269
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发表时间:
1991-01-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Suda T
Suda T
中科院分区:
其他
文献类型:
--
作者:
Kodama H;Yamasaki A;Nose M;Niida S;Ohgame Y;Abe M;Kumegawa M;Suda T

文献摘要

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骨质疏松(op/op)小鼠严重缺乏破骨细胞、单核细胞和腹膜巨噬细胞,这是由于M-CSF基因突变导致功能性巨噬细胞集落刺激因子(M-CSF)产生缺陷所致。在这项研究中,我们检测了每天5微克注射纯化的重组人M-CSF (rhM-CSF) 14天是否能治愈突变小鼠的这些缺陷。每天皮下注射2次或3次该因子后,op/op小鼠外周血单核细胞数量显著增加。相比之下,op/op小鼠长骨的骨质疏松症只需每天注射一次rhM- CSF即可完全治愈。骨干骨小梁被切除。形而上骨小梁表面可见大量破骨细胞。虽然未注射的op/op小鼠的牙胚发育受到损害,但rhM-CSF注射恢复了磨牙胚的发育,并由于骨吸收活性的恢复而导致牙齿萌出。这些结果表明M-CSF是生理条件下破骨细胞和单核/巨噬细胞分化的因素之一。
Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM- CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.