Inhibition of RANKL-induced osteoclast formation in mouse bone marrow cells by IL-12:: involvement of IFN-γ possibly induced from non-T cell population
Inhibition of RANKL-induced osteoclast formation in mouse bone marrow cells by IL-12:: involvement of IFN-γ possibly induced from non-T cell population
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DOI：
10.1016/s8756-3282(03)00213-8
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发表时间：
2003-10-01
期刊：
影响因子：
4.1
通讯作者：
Nakayama, K
中科院分区：
文献类型：
--
作者：
Nagata, N;Kitaura, H;Nakayama, K
IL-12 显示有可能抑制用巨噬细胞集落刺激因子 (M-CSF) 和 NF-kappaB 配体受体激活剂 (RANKL) 处理的小鼠骨髓细胞中的破骨细胞形成。当骨髓巨噬细胞 (BMM) 用作破骨细胞前体时，IL-12 未能抑制 M-CSF/RANKL 诱导的 BMM 破骨细胞形成。在使用 Transwell 的共培养实验中，IL-12 确实抑制了与全骨髓细胞共培养的 BMM 的破骨细胞形成。这些结果表明IL-12间接影响骨髓细胞中M-CSF/RANKL诱导的破骨细胞生成，并且IL-12对破骨细胞形成的抑制是由来自用IL-12处理的骨髓细胞的体液因子引起的。使用抗干扰素（IFN）-γ抗体和来自IFN-γ受体敲除小鼠的骨髓细胞进行的实验表明，IFN-γ可能参与抑制该系统中的破骨细胞形成。骨髓细胞中骨保护素mRNA的表达不受IL-12处理的影响。在正常小鼠的T细胞耗尽的骨髓细胞和无胸腺裸鼠的全骨髓细胞中也观察到IL-12对破骨细胞形成的抑制作用，而在B细胞耗尽的骨髓细胞中IL-12的抑制作用被部分抑制。 IL-12对M-CSF/RANKL诱导的破骨细胞生成的抑制作用并不伴随细胞死亡，与我们之前的发现相反，IL-12对M-CSF/TNF-α诱导的破骨细胞生成的抑制作用可归因于Fas和FasL介导的细胞凋亡。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
IL-12 was shown to have the potential to inhibit osteoclast formation in mouse bone marrow cells treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). When bone marrow macrophages (BMM) were used as osteoclast precursors, IL-12 failed to inhibit M-CSF/RANKL-induced osteoclast formation from BMM. In coculture experiments using transwells, IL-12 did inhibit osteoclast formation from BMM cocultured with whole bone marrow cells. These results indicated that IL-12 indirectly affected M-CSF/RANKL-induced osteoclastogenesis in bone marrow cells and that the inhibition of IL-12 on osteoclast formation was caused by a humoral factor from bone marrow cells treated with IL-12. Experiments with anti-interferon (IFN)-gamma antibody and bone marrow cells from IFN-gamma receptor knockout mice revealed that IFN-gamma might be involved in the inhibition of osteoclast formation in this system. The expression of osteoprotegerin mRNA in bone marrow cells was not affected by treatment with IL-12. The inhibitory effect of IL-12 on osteoclast formation was also seen in the T cell-depleted bone marrow cells of normal mice and the whole bone marrow cells of athymic nude mice, while the inhibitory effect of IL-12 was partially suppressed in the B cell-depleted bone marrow cells. The inhibitory effect of IL-12 on M-CSF/RANKL-induced osteoclastogenesis was not accompanied with cell death, in contrast with our previous finding that the inhibitory effect of IL-12 on M-CSF/TNF-alpha-induced osteoclastogenesis is attributable to Fas and FasL-mediated apoptosis. (C) 2003 Elsevier Science (USA). All rights reserved.