IL-10 modulates formation of osteoclasts in murine hemopoietic cultures.

IL-10 modulates formation of osteoclasts in murine hemopoietic cultures.
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DOI:
10.4049/jimmunol.157.2.936
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发表时间:
1996-07
影响因子:
4.4
通讯作者:
J. Owens;A. Gallagher;T. Chambers
J. Owens;A. Gallagher;T. Chambers
中科院分区:
医学2区
文献类型:
--
作者:
J. Owens;A. Gallagher;T. Chambers

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IL-10最初被描述为T细胞产生的细胞因子合成抑制因子,最近发现其抑制小鼠骨髓培养物中的成骨细胞分化。由于成骨细胞对破骨细胞(骨吸收细胞)的产生和调节产生重要影响,这表明细胞因子可能在骨吸收的调节中发挥作用。因此,我们测试了细胞因子对破骨细胞形成和功能的作用。我们没有发现IL-10对成熟破骨细胞的再吸收功能的影响,无论是在分离时还是在成骨细胞存在下孵育时。然而,IL-10抑制骨髓培养物和骨髓基质细胞系与造血脾细胞的共培养物中的骨吸收。在这两个系统中,骨吸收的抑制与降钙素受体阳性细胞与巨噬细胞的比例大幅降低有关,表明IL-10对破骨细胞和巨噬细胞从其共同前体的分化发挥相互作用。这种相互作用与向造血培养物中添加巨噬细胞CSF相关的作用非常相似,我们发现IL-10增加了骨髓培养物中巨噬细胞CSF mRNA的表达。IL-10对破骨细胞形成的这种有效抑制表明IL-10可能在炎症性疾病中的骨丢失的调节中起作用。
IL-10, originally described as a cytokine synthesis inhibitory factor produced by T cells, has recently been found to suppress osteoblastic differentiation in mouse bone marrow cultures. Since osteoblastic cells exert a major influence on the production and regulation of osteoclasts, the cells that resorb bone, this suggests that the cytokine might play a role in the regulation of bone resorption. We, therefore, tested the actions of the cytokine on osteoclast formation and function. We found no effect of IL-10 on the resorptive function of mature osteoclasts, either when isolated or when incubated in the presence of osteoblastic cells. However, IL-10 suppressed bone resorption in bone marrow cultures and in cocultures of bone marrow stromal cell lines with hemopoietic spleen cells. In both systems, suppression of bone resorption was associated with a substantial reduction in the ratio of calcitonin receptor-positive cells to macrophages, suggesting that IL-10 exerts a reciprocal action on the differentiation of osteoclasts and macrophages from their shared precursor. This reciprocal action is very similar to that associated with the addition of macrophage CSF to hemopoietic cultures, and we found that IL-10 increased the expression of mRNA for macrophage CSF in bone marrow cultures. This potent inhibition of osteoclast formation by IL-10 suggests that IL-10 might play a role in the modulation of bone loss in inflammatory disorders.