Morohashi T, Corboz V A, Fleisch H, Cecchini M G, Felix R
Department of Pathophysiology, University of Berne, Switzerland.
J Bone Miner Res. 1994 Mar;9(3):401-7. doi: 10.1002/jbmr.5650090316.
The in vivo administration of macrophage colony-stimulating factor (M-CSF) restores osteoclastogenesis and bone resorption in the op/op murine osteopetrosis. In vitro, exogenous M-CSF has been shown to be necessary for the generation of osteoclast-like cells in cocultures of hematopoietic and mesenchymal cells obtained from this mutant. In this study we investigated the capacity of M-CSF and other cytokines and hormones, alone or in combination, to induce bone resorption in explants of op/op metatarsals and metacarpals prelabeled with 45Ca. The effect on bone resorption was verified by counting the number of osteoclasts generated in the mineralized matrix. No osteoclast formation and no bone resorption were observed in the absence of M-CSF. M-CSF alone had only a slight effect at the high concentration of 10(4) units/ml. Addition of PTH or 1,25-(OH)2D3 together with M-CSF induced both osteoclastogenesis and bone resorption. The release of 45Ca was linear with time up to 15 days. PTH or 1,25-(OH)2D3 could not be substituted by TNF-alpha or IL-1, whereas IL-6 had a weak effect. M-CSF could not be replaced by GM-CSF. This study further emphasizes the role of M-CSF, PTH, and 1,25-(OH)2D3 in osteoclastogenesis.
在体内给予巨噬细胞集落刺激因子（M-CSF）可恢复op/op小鼠骨质疏松症中的破骨细胞生成和骨吸收。在体外，已表明外源性M-CSF对于从该突变体获得的造血细胞和间充质细胞共培养物中破骨细胞样细胞的生成是必需的。在本研究中，我们研究了M-CSF和其他细胞因子及激素单独或联合作用于预先用45Ca标记的op/op跖骨和掌骨外植体诱导骨吸收的能力。通过计数矿化基质中产生的破骨细胞数量来验证对骨吸收的影响。在没有M-CSF的情况下，未观察到破骨细胞形成和骨吸收。单独的M-CSF在10(4)单位/ml的高浓度下仅有轻微作用。PTH或1,25-(OH)2D3与M-CSF一起添加可诱导破骨细胞生成和骨吸收。45Ca的释放直至15天与时间呈线性关系。PTH或1,25-(OH)2D3不能被TNF-α或IL-1替代，而IL-6的作用较弱。GM-CSF不能替代M-CSF。本研究进一步强调了M-CSF、PTH和1,25-(OH)2D3在破骨细胞生成中的作用。
