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

干扰素-ζ/利米丁是一种I型干扰素，在小鼠中与其他I型干扰素利用相同的干扰素-α/β受体。在此，我们检测了干扰素-ζ/利米丁对体外破骨细胞生成的影响。干扰素-C/利米丁可抑制可溶性受体激活剂核因子-kB配体(SRANKL)或肿瘤坏死因子-a(肿瘤坏死因子-a)诱导的小鼠巨噬细胞破骨细胞前体细胞的破骨细胞分化。干扰素-C/LIMIT可刺激破骨细胞前体细胞RNA依赖性蛋白激酶R(PKR)mRNA的表达，减少c-Fos蛋白的表达，但不影响c-Fos的mRNA水平。与c-Fos蛋白生成减少一致的是，干扰素-C/利米丁降低了活化T细胞核因子c1(NFATc1)的mRNA表达。此外，PKR基因敲除部分恢复了干扰素-C/LIMIT抑制的破骨细胞生成。另一方面，与其对破骨细胞前体细胞的作用不同，干扰素-ζ/利米丁不影响抗CD3抗体激活的小鼠T细胞的增殖和NFATc1mRNA的表达，也不影响RANKL和肿瘤坏死因子-α的产生，提示与干扰素-α和-β相比，具有更有限的细胞类型特异性。因此，我们重新检测了干扰素-C/利米丁对破骨细胞生成、NFATc1、c-Fos和PKR基因表达的依赖关系。数据显示，效率提高了1000倍。此外，对干扰素-C/LIMIT和干扰素-β的作用进行了比较。结果表明，干扰素-C/LIMIT对破骨细胞的抑制作用强于其他I型干扰素。

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.