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

干扰素(IFN)-ζ/限制蛋白是一种i型IFN，在小鼠体内利用与其他i型IFN相同的IFN-α/β受体。在这里，我们研究了IFN-ζ/限制对体外破骨细胞生成的影响。IFN-C/限制蛋白抑制NF-KB配体可溶性受体激活剂（sRANKL）或肿瘤坏死因子-a （TNF-α）诱导的小鼠巨噬细胞破骨细胞前体的破骨生成。IFN-C/限制受刺激的rna依赖性蛋白激酶R (PKR) mRNA表达和减少c-Fos蛋白的产生，而不影响破骨细胞前体c-Fos mRNA水平。与减少c-Fos蛋白的产生一致，IFN-C/限制蛋白降低了活化T细胞核因子c1 (NFATc1) mRNA的表达。此外，PKR敲除部分恢复了IFN-C/限制的破骨细胞生成。另一方面，与对破骨细胞前体的影响不同，IFN-ζ/限制蛋白不影响抗cd3抗体激活的小鼠T细胞的增殖、NFATc1 mRNA的表达或RANKL和TNF-α的产生，这表明与IFN-α和-β相比，IFN-ζ/限制蛋白具有更有限的细胞类型特异性。近期生产批次IFN-C/limit的变化对破骨细胞的抑制作用更为有效。因此，IFN-C/限制是否对破骨细胞发生有依赖作用，我们重新检测了NFATc1、c-Fos和PKR的mRNA表达。数据显示效率提高了1000倍。此外，比较了IFN- c /limit和IFN-β的作用。结果表明，IFN-C/limit in对破骨细胞生成的抑制作用强于其他i型ifn。

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.