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） - ζ/极限，I型IFN，使用与小鼠中其他类型I IFN相同的IFN-α/β受体。在这里，我们检查了IFN-ζ/极限对体外破骨细胞生成的影响。 IFN-C/极限抑制了由NF-KB配体（SRANKL）固体受体激活剂（SRANKL）或肿瘤坏死因子A（TNF-α）诱导的小鼠巨噬细胞发生前体的破骨细胞生成。 IFN-C/限制在刺激的RNA依赖性蛋白激酶R（PKR）mRNA表达并改善C-FOS蛋白的产生，而不会影响破骨细胞前体中的C-FOS mRNA水平。与C-FOS蛋白的生产降低一致，IFN-C/极限降低了活化T细胞C1（NFATC1）mRNA表达的核因子。此外，PKR敲低的部分恢复了IFN-C/极限。另一方面，IFN-C/极限抑制了其对破骨细胞前体的影响，IFN-ζ/极限不影响抗CD3抗体激活的小鼠T细胞的抗CD3抗体的增殖，而NFATC1 MRNA或其生产的nFATC1 mRNA或TNF-rna tenge tenge anf and tenge and tenge的表达则更多，随着IFN-α和-β的生产批次变化，IFN-C/限制对破骨细胞生成的影响更有效。因此，确实会重新检查IFN-C/极限破骨细胞生成，NFATC1，C-FOS和PKR的mRNA表达。效率提高了1000倍的数据。此外，比较IFN-C/限制和IFN-β的影响。结果表明，与其他I型IFN相比，IFN-C/限制是破骨细胞生成的潜在抑制剂。