IL-1α stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts

IL-1α stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts
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DOI:
10.1016/j.lfs.2004.10.079
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发表时间:
2005-06-24
期刊:
影响因子:
6.1
通讯作者:
Ito, K
Ito, K
中科院分区:
医学2区
文献类型:
--
作者:
Tanabe, N;Maeno, M;Ito, K

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白细胞介素-1 α(IL-1 α)是参与与炎症相关的骨丢失的最有效的骨吸收因子之一。我们检测了炎症介质IL-1 α对大鼠成骨细胞中巨噬细胞集落刺激因子(M-CSF)、骨保护素(OPG)和前列腺素E-2(PGE(2))表达的影响,以及IL-1 α对破骨细胞样细胞形成的间接影响。将成骨细胞在含有10%胎牛血清的最低必需培养基中培养长达14天,所述最低必需培养基含有或不含有100单位/ml的IL-1 α。采用实时荧光定量聚合酶链反应(PCR)和蛋白质印迹法(Western blot)分别测定M-CSF和OPG的mRNA和蛋白质表达水平。用酶联免疫吸附试验测定PGE(2)表达。用抗酒石酸酸性磷酸酶(TRAP)染色培养物中的破骨细胞前体,用IL-1 α处理的成骨细胞和可溶性NF-κ B配体受体激活剂(RANKL)的条件培养基评估破骨细胞样细胞的形成。IL-1 α诱导成骨细胞M-CSF和PGE(2)表达增加,OPG表达减少。含有由IL-1 α处理的成骨细胞产生的M-CSF和PGE 2以及可溶性RANKL的条件培养基增加了破骨细胞前体的TRAP染色。这些结果表明,IL-1 α刺激破骨细胞样细胞的形成,通过增加M-CSF和PGE 2的生产,并减少OPG的生产由成骨细胞。(c)2005年爱思唯尔公司All rights reserved.
Interleukin-1 alpha (IL-1 alpha) is one of the most potent bone-resorbing factors involved in the bone loss that is associated with inflammation. We examined the effect of the inflammatory mediator IL-1 alpha on the expression of macrophage colony-stimulating factor (M-CSF), osteoprotegerin (OPG), and prostaglandin E-2 (PGE(2)) in rat osteoblasts, and the indirect effect of IL-1 alpha on the formation of osteoclast-like cells. Osteoblasts were cultured in a-minimum essential medium containing 10% fetal bovine serum with or without 100 units/ml of IL-1 alpha for up to 14 days. The gene and protein expression of M-CSF and OPG were estimated by determining mRNA levels using the real-time polymerase chain reaction and protein levels using Western blot analysis. PGE(2) expression was determined using an enzyme-linked immunosorbent assay. The formation of osteoclast-like cells was estimated using tartrate-resistant acid phosphatase (TRAP) staining of osteoclast precursors in culture with conditioned medium from IL-1 alpha-treated osteoblasts and the soluble receptor activator of NF-kappa B ligand (RANKL). M-CSF and PGE(2) expression in osteoblasts increased markedly in cells cultured with IL-1 alpha, whereas OPG expression decreased. The conditioned medium containing M-CSF and PGE2 produced by IL-1 alpha-treated osteoblasts and soluble RANKL increased the TRAP staining of osteoclast precursors. These results suggest that IL-1 alpha stimulated the formation of osteoclast-like cells via an increase in M-CSF and PGE2 production, and a decrease in OPG production by osteoblasts. (c) 2005 Elsevier Inc. All rights reserved.