Lee Sun-Kyeong, Kalinowski Judith F, Jastrzebski Sandra L, Puddington Lynn, Lorenzo Joseph A
Department of Medicine, The University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Endocrinology. 2003 Aug;144(8):3524-31. doi: 10.1210/en.2002-221057.
We examined the direct effects of IL-7 on osteoclastogenesis in murine bone marrow cultures, using cells from wild-type and IL-7- and IL-7 receptor (IL-7R)-deficient mice. IL-7 inhibited osteoclast-like cells (OCL) formation in macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL)-stimulated (both at 30 ng/ml) murine bone marrow cultures. Significant inhibitory effects were seen at 1 ng/ml (57%) and 10 ng/ml (86%). IL-7 also inhibited (P < 0.05) OCL formation in bone marrow cultures that were stimulated with vitamin D(3) (10(-8) M, 60%), bovine PTH (bPTH) (100 ng/ml, 54%), or RANKL alone (30 ng/ml, 50%). IL-7 (10 ng/ml) increased expression of the B lymphocyte marker B220 from 40-86% of total nonadherent cells in cultures treated with M-CSF and RANKL. Bone marrow cells from IL-7-deficient [IL-7 knockout (KO)] mice showed a significant (P < 0.05) increase in tartrate-resistant acid phosphatase(+) OCL numbers in cultures that were stimulated with vitamin D(3) (136 +/- 13.3%), bPTH (196 +/- 18.8%), or M-CSF and RANKL (160 +/- 7.2%). In contrast, in vitro osteoclast formation in bone marrow from IL-7R-deficient (IL-7R KO) mice showed a significant decrease in tartrate-resistant acid phosphatase(+) OCL numbers in cultures that were stimulated with vitamin D(3), PTH, RANKL, or M-CSF and RANKL. These results demonstrate that there are differences in the mechanisms regulating OCL formation between IL-7 KO and IL-7R KO cells. It seems that IL-7 is a direct inhibitor of OCL formation in vitro, based on results of adding IL-7 to wild-type cultures and the responses of IL-7 KO cells. It is unknown why IL-7R KO cells behave differently from IL-7 KO cells in vitro. However, it is possible that additional cytokines interact with IL-7R and that loss of these signals contributes to the responses of IL-7R KO cells. Alternatively, IL-7 may interact with multiple receptors.
我们使用来自野生型、白细胞介素7（IL-7）缺陷型和IL-7受体（IL-7R）缺陷型小鼠的细胞，研究了IL-7对小鼠骨髓培养中破骨细胞生成的直接影响。在巨噬细胞集落刺激因子（M-CSF）和核因子κB受体活化因子配体（RANKL）（均为30 ng/ml）刺激的小鼠骨髓培养物中，IL-7抑制破骨细胞样细胞（OCL）的形成。在1 ng/ml（57%）和10 ng/ml（86%）时可见显著的抑制作用。IL-7还抑制（P<0.05）用维生素D3（10-8 M，60%）、牛甲状旁腺激素（bPTH）（100 ng/ml，54%）或单独的RANKL（30 ng/ml，50%）刺激的骨髓培养物中OCL的形成。IL-7（10 ng/ml）使M-CSF和RANKL处理的培养物中总非贴壁细胞中B淋巴细胞标志物B220的表达从40%增加到86%。在维生素D3（136±13.3%）、bPTH（196±18.8%）或M-CSF和RANKL（160±7.2%）刺激的培养物中，IL-7缺陷型[IL-7基因敲除（KO）]小鼠的骨髓细胞中抗酒石酸酸性磷酸酶阳性OCL数量显著增加（P<0.05）。相反，在维生素D3、甲状旁腺激素、RANKL或M-CSF和RANKL刺激的培养物中，IL-7R缺陷型（IL-7R KO）小鼠骨髓中的体外破骨细胞形成显示抗酒石酸酸性磷酸酶阳性OCL数量显著减少。这些结果表明，IL-7 KO细胞和IL-7R KO细胞在调节OCL形成的机制上存在差异。基于将IL-7添加到野生型培养物的结果以及IL-7 KO细胞的反应，似乎IL-7是体外OCL形成的直接抑制剂。目前尚不清楚为什么IL-7R KO细胞在体外的行为与IL-7 KO细胞不同。然而，可能有其他细胞因子与IL-7R相互作用，并且这些信号的缺失导致了IL-7R KO细胞的反应。或者，IL-7可能与多种受体相互作用。
