The critical role of IL-34 in osteoclastogenesis.-猫眼课题宝

DOI：

10.1371/journal.pone.0018689

发表时间：

2011-04-08

期刊：

PloS one

影响因子：

3.7

通讯作者：

中科院分区：

综合性期刊3区

文献类型：

作者：

Chen Z;Buki K;Vääräniemi J;Gu G;Väänänen HK

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072988/?report=classic

人们普遍认为，破骨细胞形成所需的细胞因子是M-CSF（也称为CSF-1）和RANKL。最近，一种新的细胞因子，命名为IL-34，已被确定为CSF 1 R的另一种配体。本研究旨在探讨这种新的细胞因子的生物学功能，特别是破骨细胞生成和骨代谢。我们生产了重组小鼠IL-34，并发现它与RANKL一起诱导小鼠脾细胞和骨髓细胞剂量依赖性地形成破骨细胞，这些细胞也显示出骨吸收活性。它还促进破骨细胞从人外周血单核细胞分化。最后，我们表明，全身给予IL-34的小鼠增加了CD 11b+细胞的比例，减少了骨小梁质量。我们的数据表明，IL-34是破骨细胞生成的另一个重要参与者，因此可能在骨疾病中发挥作用。针对CSF 1/CSF 1 R的靶向治疗策略已经被开发出来，其中一些已经进入临床前和临床研究，用于治疗炎症性疾病。我们的研究结果强烈表明，有必要重新审视这些策略，因为它们可能提供一个新的潜在的药物靶点，除了在炎症性疾病的治疗中的作用，骨代谢的调节。

It has been widely believed that the cytokines required for osteoclast formation are M-CSF (also known as CSF-1) and RANKL. Recently, a novel cytokine, designated IL-34, has been identified as another ligand of CSF1R. This study was to explore the biological function, specifically osteoclastogenesis and bone metabolism, of the new cytokine. We produced recombinant mouse IL-34 and found that together with RANKL it induces the formation of osteoclasts both from splenocytes as well as dose-dependently from bone marrow cells in mouse and these cells also revealed bone resorption activity. It also promotes osteoclast differentiation from human peripheral blood mononucleated cells. Finally, we show that systemic administration of IL-34 to mice increases the proportion of CD11b+ cells and reduces trabecular bone mass. Our data indicate that IL-34 is another important player in osteoclastogenesis and thus may have a role in bone diseases. Strategies of targeting CSF1/CSF1R have been developed and some of them are already in preclinical and clinical studies for treatment of inflammatory diseases. Our results strongly suggest the need to revisit these strategies as they may provide a new potential pharmaceutical target for the regulation of bone metabolism in addition to their role in the treatment of inflammatory diseases.