Studies of limitin as a therapeutic agent for periodontitis : analysis of mechanisms of inhibition of osteoclastogenesis

Limitin作为牙周炎治疗剂的研究：破骨细胞生成抑制机制分析

• 批准号: 18592007
• 负责人: SATO Takuya
• 金额: $ 2.55万
• 依托单位: Meikai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592007/
• 关键词: limitin; type-linterferon; osteoclasts; periodontitis; 1型インターフェロン; 骨吸収

Interferon (IFN)-ζ/limitin, a type-I IFN, utilizes the same IFN-α/β receptor as other type-I IFNs in mice. Here we examined the effects of IFN-ζ/limitin on osteoclastogenesis in vitro. IFN-C/limitin inhibited osteoclastogenesis from mouse macrophage osteoclast precursors induced by soluble receptor activator of NF-KB ligand (sRANKL) or tumor necrosis factor-a (TNF-α). IFN-C/limit in stimulated RNA-dependent protein kinase R (PKR) mRNA expression and decreased c-Fos protein production without affecting the c-Fos mRNA level in osteoclast precursors. Consistent with the decreased production of c-Fos protein, IFN-C/limitin decreased nuclear factor of activated T cells c1 (NFATc1) mRNA expression. Moreover, PKR knock-down partially restored the osteoclastogenesis inhibited by IFN-C/limit in. On the other hand, distinct from its effect on osteoclast precursors, IFN-ζ/limitin did not influence proliferation of anti-CD3 antibody-activated mouse T cells or their expression of NFATc1 mRNA or production of RANKL and TNF-α, suggesting a more restricted cell-type specificity compared with IFN-α and -β.Recent change of IFN-C/limit in production lot showed more efficient inhibitory effects on osteoclastogenesis. Therefore, does dependent effects of IFN-C/limitin on osteoclastogenesis, mRNA expressions of NFATc1, c-Fos and PKR were re-examined. The data showed on 1000 times higher efficiencies. In addition, effects of IFN-C/limit in and IFN-β compared. The results showed that IFN-C/limit in were more potent inhibitor of osteoclastogenesis than other type-I IFNs.

干扰素（IFN）-γ/限制素是一种I型IFN，在小鼠中利用与其他I型IFN相同的IFN-α/β受体。在这里，我们研究了IFN-γ/limitin对体外破骨细胞生成的影响。IFN-C/limitin抑制可溶性NF-κ B受体激活剂配体（sRANKL）或肿瘤坏死因子-α（TNF-α）诱导的小鼠巨噬细胞破骨细胞前体的破骨细胞生成。IFN-C/限制刺激RNA依赖性蛋白激酶R（PKR）mRNA的表达和减少c-Fos蛋白的产生，而不影响破骨细胞前体中c-Fos mRNA的水平。与c-Fos蛋白产生减少一致，IFN-C/limitin降低活化T细胞核因子c1（NFATc 1）mRNA表达。此外，PKR敲低部分恢复了IFN-C/limit抑制的破骨细胞生成。另一方面，与其对破骨细胞前体的作用不同，IFN-α/limitin不影响抗CD 3抗体激活的小鼠T细胞的增殖或其NFATc 1 mRNA的表达或RANKL和TNF-α的产生，这表明与IFN-α和-β相比，IFN-α/limitin具有更有限的细胞类型特异性。因此，我们重新研究了IFN-C/limitin对破骨细胞生成、NFATc 1、c-Fos和PKR mRNA表达的剂量依赖性影响。数据显示效率提高了1000倍。此外，还将IFN-C/限与IFN-β的作用进行了比较。结果表明，IFN-C/limit in对破骨细胞生成的抑制作用强于其它I型IFN。

项目成果

Production of IL-7 is increased in ovariectomized mice, but not RANKL mRNA expression by osteoblasts/stromal cells in bone, and IL-7 enhances generation of osteoclast precursors in vitro

• DOI: 10.1007/s00774-006-0723-y
• 发表时间: 2007-01-01
• 期刊: JOURNAL OF BONE AND MINERAL METABOLISM
• 影响因子: 3.3
• 作者: Sato, Takuya;Watanabe, Ken;Hakeda, Yoshiyuki
• 通讯作者: Hakeda, Yoshiyuki