Felix R, Cecchini M G, Fleisch H
Department of Pathophysiology, University of Berne, Switzerland.
Endocrinology. 1990 Nov;127(5):2592-4. doi: 10.1210/endo-127-5-2592.
The op/op variant of murine osteopetrosis is a recessive mutation characterized by impaired bone resorption due to lack of osteoclasts. Cultured osteoblasts and fibroblasts from this mutant do not secrete M-CSF activity and resident macrophages are absent in bone marrow. This failure has been related to a mutation within the M-CSF coding region. We report now that the administration of recombinant human M-CSF (rhM-CSF) corrects in vivo the impaired bone resorption in this animal. The treatment restores the bone marrow cavity virtually absent in the op/op animal and induces the appearance of resorbing osteoclasts and of resident bone marrow macrophages. This proves that the deficiency of M-CSF is the cause of the op/op bone disorder and that this cytokine is directly or indirectly necessary for physiological osteoclastogenesis, the resulting bone resorption and for the establishment of bone marrow hemopoiesis.
小鼠骨硬化症的op/op变异型是一种隐性突变,其特征是由于破骨细胞缺乏导致骨吸收受损。来自该突变体的培养成骨细胞和成纤维细胞不分泌M-CSF活性,骨髓中也没有常驻巨噬细胞。这种缺陷与M-CSF编码区域内的突变有关。我们现在报告,给予重组人M-CSF(rhM-CSF)可在体内纠正该动物受损的骨吸收。该治疗恢复了op/op动物几乎不存在的骨髓腔,并诱导出现吸收性破骨细胞和常驻骨髓巨噬细胞。这证明M-CSF缺乏是op/op骨病的原因,并且这种细胞因子对于生理性破骨细胞生成、由此产生的骨吸收以及骨髓造血的建立直接或间接是必需的。